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Boicean A, Boeras I, Birsan S, Ichim C, Todor SB, Onisor DM, Brusnic O, Bacila C, Dura H, Roman-Filip C, Ognean ML, Tanasescu C, Hasegan A, Bratu D, Porr C, Roman-Filip I, Neamtu B, Fleaca SR. In Pursuit of Novel Markers: Unraveling the Potential of miR-106, CEA and CA 19-9 in Gastric Adenocarcinoma Diagnosis and Staging. Int J Mol Sci 2024; 25:7898. [PMID: 39063140 PMCID: PMC11277351 DOI: 10.3390/ijms25147898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 07/10/2024] [Accepted: 07/12/2024] [Indexed: 07/28/2024] Open
Abstract
Gastric cancer stands as the fourth leading cause of cancer-related deaths globally, primarily comprising adenocarcinomas, categorized by anatomic location and histologic type. Often diagnosed at advanced stages, gastric cancer prognosis remains poor. To address the critical need for accurate tumoral markers for gastric cancer diagnosis, we conducted a study to assess classical markers like CEA and CA-19-9 alongside the novel marker miR-106. Our investigation revealed distinct dynamics of these markers compared to non-cancerous groups, although no disparities were observed across different disease stages. Univariable and multivariable logistic regression analyses demonstrated that elevated levels of miR-106, CEA and CA 19-9 were predictive of a positive histopathological exam, with the respective odds ratios of 12.032 (95% CI: 1.948-74.305), 30 (95% CI: 3.141-286.576), and 55.866 (95% CI: 4.512-691.687). Subsequently, we utilized predicted probabilities from regression models to construct receiver operating characteristic (ROC) curves, identifying CA 19-9 as the optimal predictor for gastric adenocarcinoma diagnosis when considering age and gender, with an area under the curve (AUC) of 0.936 (p < 0.001). Hence, classical markers exhibit superior performance compared to the novel marker miR-106 in predicting gastric adenocarcinoma.
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Affiliation(s)
- Adrian Boicean
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania; (A.B.); (C.I.); (C.B.); (H.D.); (C.R.-F.); (M.L.O.); (C.T.); (A.H.); (D.B.); (S.R.F.)
| | - Ioana Boeras
- Molecular Biology Laboratory of the Applied Ecology Research Center, Faculty of Sciences, Lucian Blaga University of Sibiu, 550012 Sibiu, Romania
- Faculty of Social Sciences, Lucian Blaga University of Sibiu, 550012 Sibiu, Romania
| | - Sabrina Birsan
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania; (A.B.); (C.I.); (C.B.); (H.D.); (C.R.-F.); (M.L.O.); (C.T.); (A.H.); (D.B.); (S.R.F.)
| | - Cristian Ichim
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania; (A.B.); (C.I.); (C.B.); (H.D.); (C.R.-F.); (M.L.O.); (C.T.); (A.H.); (D.B.); (S.R.F.)
| | - Samuel Bogdan Todor
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania; (A.B.); (C.I.); (C.B.); (H.D.); (C.R.-F.); (M.L.O.); (C.T.); (A.H.); (D.B.); (S.R.F.)
| | - Danusia Maria Onisor
- Department of Gastroenterology, University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Târgu Mures, Romania; (D.M.O.); (O.B.)
| | - Olga Brusnic
- Department of Gastroenterology, University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Târgu Mures, Romania; (D.M.O.); (O.B.)
| | - Ciprian Bacila
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania; (A.B.); (C.I.); (C.B.); (H.D.); (C.R.-F.); (M.L.O.); (C.T.); (A.H.); (D.B.); (S.R.F.)
| | - Horatiu Dura
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania; (A.B.); (C.I.); (C.B.); (H.D.); (C.R.-F.); (M.L.O.); (C.T.); (A.H.); (D.B.); (S.R.F.)
| | - Corina Roman-Filip
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania; (A.B.); (C.I.); (C.B.); (H.D.); (C.R.-F.); (M.L.O.); (C.T.); (A.H.); (D.B.); (S.R.F.)
| | - Maria Livia Ognean
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania; (A.B.); (C.I.); (C.B.); (H.D.); (C.R.-F.); (M.L.O.); (C.T.); (A.H.); (D.B.); (S.R.F.)
| | - Ciprian Tanasescu
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania; (A.B.); (C.I.); (C.B.); (H.D.); (C.R.-F.); (M.L.O.); (C.T.); (A.H.); (D.B.); (S.R.F.)
| | - Adrian Hasegan
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania; (A.B.); (C.I.); (C.B.); (H.D.); (C.R.-F.); (M.L.O.); (C.T.); (A.H.); (D.B.); (S.R.F.)
| | - Dan Bratu
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania; (A.B.); (C.I.); (C.B.); (H.D.); (C.R.-F.); (M.L.O.); (C.T.); (A.H.); (D.B.); (S.R.F.)
| | - Corina Porr
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania
| | - Iulian Roman-Filip
- Department of Neurology, “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology, 540136 Targu Mures, Romania
| | - Bogdan Neamtu
- Pediatric Research Department, Pediatric Clinical Hospital Sibiu, 550166 Sibiu, Romania;
| | - Sorin Radu Fleaca
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania; (A.B.); (C.I.); (C.B.); (H.D.); (C.R.-F.); (M.L.O.); (C.T.); (A.H.); (D.B.); (S.R.F.)
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Wang T, Jin Y, Wang M, Chen B, Sun J, Zhang J, Yang H, Deng X, Cao X, Wang L, Tang Y. SALL4 in gastrointestinal tract cancers: upstream and downstream regulatory mechanisms. Mol Med 2024; 30:46. [PMID: 38584262 PMCID: PMC11000312 DOI: 10.1186/s10020-024-00812-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 03/20/2024] [Indexed: 04/09/2024] Open
Abstract
Effective therapeutic targets and early diagnosis are major challenges in the treatment of gastrointestinal tract (GIT) cancers. SALL4 is a well-known transcription factor that is involved in organogenesis during embryonic development. Previous studies have revealed that SALL4 regulates cell proliferation, survival, and migration and maintains stem cell function in mature cells. Additionally, SALL4 overexpression is associated with tumorigenesis. Despite its characterization as a biomarker in various cancers, the role of SALL4 in GIT cancers and the underlying mechanisms are unclear. We describe the functions of SALL4 in GIT cancers and discuss its upstream/downstream genes and pathways associated with each cancer. We also consider the possibility of targeting these genes or pathways as potential therapeutic options for GIT cancers.
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Affiliation(s)
- Tairan Wang
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China
| | - Yan Jin
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China
| | - Mengyao Wang
- First Clinical Medical College, Xinxiang Medical University, Xinxiang, 453003, China
| | - Boya Chen
- First Clinical Medical College, Xinxiang Medical University, Xinxiang, 453003, China
| | - Jinyu Sun
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China
| | - Jiaying Zhang
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China
| | - Hui Yang
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China
| | - Xinyao Deng
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China
| | - Xingyue Cao
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China
| | - Lidong Wang
- State Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key, Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, China.
| | - Yuanyuan Tang
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China.
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3
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Akbari A, Noorbakhsh Varnosfaderani SM, Haeri MS, Fathi Z, Aziziyan F, Yousefi Rad A, Zalpoor H, Nabi-Afjadi M, Malekzadegan Y. Autophagy induced by Helicobacter Pylori infection can lead to gastric cancer dormancy, metastasis, and recurrence: new insights. Hum Cell 2024; 37:139-153. [PMID: 37924488 DOI: 10.1007/s13577-023-00996-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 10/11/2023] [Indexed: 11/06/2023]
Abstract
According to the findings of recent research, Helicobacter Pylori (H. pylori) infection is not only the primary cause of gastric cancer (GC), but it is also linked to the spread and invasion of GC through a number of processes and factors that contribute to virulence. In this study, we discussed that H. pylori infection can increase autophagy in GC tumor cells, leading to poor prognosis in such patients. Until now, the main concerns have been focused on H. pylori's role in GC development. According to our hypothesis, however, H. pylori infection may also lead to GC dormancy, metastasis, and recurrence by stimulating autophagy. Therefore, understanding how H. pylori possess these processes through its virulence factors and various microRNAs can open new windows for providing new prevention and/or therapeutic approaches to combat GC dormancy, metastasis, and recurrence which can occur in GC patients with H. pylori infection with targeting autophagy and eradicating H. pylori infection.
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Affiliation(s)
- Abdullatif Akbari
- Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | | | - Melika Sadat Haeri
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Zeinab Fathi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Aziziyan
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Ali Yousefi Rad
- Department of Biochemistry, Falavarjan Branch, Islamic Azad University, Isfahan, Iran
| | - Hamidreza Zalpoor
- Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
| | - Mohsen Nabi-Afjadi
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
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Pelizzaro F, Cardin R, Sarasini G, Minotto M, Carlotto C, Fassan M, Palo M, Farinati F, Zingone F. Crosstalk between MicroRNAs and Oxidative Stress in Coeliac Disease. Inflamm Intest Dis 2024; 9:11-21. [PMID: 38298886 PMCID: PMC10827301 DOI: 10.1159/000536107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 12/29/2023] [Indexed: 02/02/2024] Open
Abstract
MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in regulating gene expression. Many studies, mostly conducted on pediatric patients, suggested that oxidative stress and several miRNAs may play an important role in coeliac disease (CeD) pathogenesis. However, the interplay between oxidative stress and miRNA regulatory functions in CeD remains to be clarified. In this review, we aimed to perform a literature review on the role of miRNAs and oxidative stress in adult CeD patients and to analyze their potential interactions. In this direction, we also reported the preliminary results of a pilot study we recently performed.
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Affiliation(s)
- Filippo Pelizzaro
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale-Università di Padova, Padua, Italy
| | - Romilda Cardin
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy
| | - Giulia Sarasini
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy
| | - Milena Minotto
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy
| | - Chiara Carlotto
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy
| | - Matteo Fassan
- Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Padua, Italy
- Veneto Institute of Oncology IOV, IRCCS, Padua, Italy
| | - Michela Palo
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale-Università di Padova, Padua, Italy
| | - Fabiana Zingone
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale-Università di Padova, Padua, Italy
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5
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Muniandy S, Few LL, Khoo BY, Hassan SA, Yvonne-Τee GB, See Too WC. Dysregulated expression of miR‑367 in disease development and its prospects as a therapeutic target and diagnostic biomarker (Review). Biomed Rep 2023; 19:91. [PMID: 37901877 PMCID: PMC10603372 DOI: 10.3892/br.2023.1673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 09/20/2023] [Indexed: 10/31/2023] Open
Abstract
MicroRNA (miR)-367 has a wide range of functions in gene regulation and as such plays a critical role in cell proliferation, differentiation and development, making it an essential molecule in various physiological processes. miR-367 belongs to the miR-302/367 cluster and is located in the intronic region of human chromosome 4 on the 4q25 locus. Dysregulation of miR-367 is associated with various disease conditions, including cancer, inflammation and cardiac conditions. Moreover, miR-367 has shown promise both as a tumor suppressor and a potential diagnostic biomarker for breast, gastric and prostate cancer. The elucidation of the essential role of miR-367 in inflammation, development and cardiac diseases emphasizes its versatility in regulating various physiological processes beyond cancer biology. However, further research is necessary to fully understand the complex regulatory mechanisms involving miR-367 in different physiological and pathological contexts. In conclusion, the versatility and significance of miR-367 makes it a promising candidate for further study and in the development of new diagnostic and therapeutic strategies.
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Affiliation(s)
- Shaleniprieya Muniandy
- School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
| | - Ling Ling Few
- School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
| | - Boon Yin Khoo
- Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang 11800, Malaysia
| | - Siti Asma' Hassan
- School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
| | - Get Bee Yvonne-Τee
- School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
| | - Wei Cun See Too
- School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
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Low YH, Loh CJL, Peh DYY, Chu AJM, Han S, Toh HC. Pathogenesis and therapeutic implications of EBV-associated epithelial cancers. Front Oncol 2023; 13:1202117. [PMID: 37901329 PMCID: PMC10600384 DOI: 10.3389/fonc.2023.1202117] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 09/07/2023] [Indexed: 10/31/2023] Open
Abstract
Epstein-Barr virus (EBV), one of the most common human viruses, has been associated with both lymphoid and epithelial cancers. Undifferentiated nasopharyngeal carcinoma (NPC), EBV associated gastric cancer (EBVaGC) and lymphoepithelioma-like carcinoma (LELC) are amongst the few common epithelial cancers that EBV has been associated with. The pathogenesis of EBV-associated NPC has been well described, however, the same cannot be said for primary pulmonary LELC (PPLELC) owing to the rarity of the cancer. In this review, we outline the pathogenesis of EBV-associated NPC and EBVaGCs and their recent advances. By drawing on similarities between NPC and PPLELC, we then also postulated the pathogenesis of PPLELC. A deeper understanding about the pathogenesis of EBV enables us to postulate the pathogenesis of other EBV associated cancers such as PPLELC.
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Affiliation(s)
- Yi Hua Low
- Duke-NUS Medical School, Singapore, Singapore
| | | | - Daniel Yang Yao Peh
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Axel Jun Ming Chu
- Singapore Health Services Internal Medicine Residency Programme, Singapore, Singapore
| | - Shuting Han
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Han Chong Toh
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
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Huang BS, Chen CT, Yeh CC, Fan TY, Chen FY, Liou JM, Shun CT, Wu MS, Chow LP. miR-21 Targets ASPP2 to Inhibit Apoptosis via CHOP-Mediated Signaling in Helicobacter pylori-Infected Gastric Cancer Cells. JOURNAL OF ONCOLOGY 2023; 2023:6675265. [PMID: 37547633 PMCID: PMC10403333 DOI: 10.1155/2023/6675265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 06/05/2023] [Accepted: 06/21/2023] [Indexed: 08/08/2023]
Abstract
Helicobacter pylori (H. pylori) infection affects cell survival pathways, including apoptosis and proliferation in host cells, and disruption of this balance is the key event in the development of H. pylori-induced gastric cancer (HPGC). H. pylori infection induces alterations in microRNAs expression that may be involved in GC development. Bioinformatic analysis showed that microRNA-21 (miR-21) is significantly upregulated in HPGC. Furthermore, quantitative proteomics and in silico prediction were employed to identify potential targets of miR-21. Following functional enrichment and clustered interaction network analyses, five candidates of miR-21 targets, PDCD4, ASPP2, DAXX, PIK3R1, and MAP3K1, were found across three functional clusters in association with cell death and survival, cellular movement, and cellular growth and proliferation. ASPP2 is inhibited by H. pylori-induced miR-21 overexpression. Moreover, ASPP2 levels are inversely correlated with miR-21 levels in HPGC tumor tissues. Thus, ASPP2 was identified as a miR-21 target in HPGC. Here, we observed that H. pylori-induced ASPP2 suppression enhances resistance to apoptosis in GC cells using apoptosis assays. Using protein interaction network and coimmunoprecipitation assay, we identified CHOP as a direct mediator of the ASPP2 proapoptotic activity in H. pylori-infected GC cells. Mechanistically, ASPP2 suppression promotes p300-mediated CHOP degradation, in turn inhibiting CHOP-mediated transcription of Noxa, Bak, and suppression of Bcl-2 to enact antiapoptosis in the GC cells after H. pylori infection. Clinicopathological analysis revealed correlations between decreased ASPP2 expression and higher HPGC risk and poor prognosis. In summary, the discovery of H. pylori-induced antiapoptosis via miR-21-mediated suppression of ASPP2/CHOP-mediated signaling provides a novel perspective for developing HPGC management and treatment.
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Affiliation(s)
- Bo-Shih Huang
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chih-Ta Chen
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chao-Chi Yeh
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ting-Yu Fan
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Fang-Yun Chen
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Jyh-Ming Liou
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Tung Shun
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Lu-Ping Chow
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
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Fathi D, Elballal MS, Elesawy AE, Abulsoud AI, Elshafei A, Elsakka EG, Ismail A, El-Mahdy HA, Elrebehy MA, Doghish AS. An emphasis on the interaction of signaling pathways highlights the role of miRNAs in the etiology and treatment resistance of gastric cancer. Life Sci 2023; 322:121667. [PMID: 37023952 DOI: 10.1016/j.lfs.2023.121667] [Citation(s) in RCA: 45] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 04/01/2023] [Accepted: 04/03/2023] [Indexed: 04/07/2023]
Abstract
Gastric cancer (GC) is 4th in incidence and mortality rates globally. Several genetic and epigenetic factors, including microRNAs (miRNAs), affect its initiation and progression. miRNAs are short chains of nucleic acids that can regulate several cellular processes by controlling their gene expression. So, dysregulation of miRNAs expressions is associated with GC initiation, progression, invasion capacity, apoptosis evasions, angiogenesis, promotion and EMT enhancement. Of important pathways in GC and controlled by miRNAs are Wnt/β-catenin signaling, HMGA2/mTOR/P-gp, PI3K/AKT/c-Myc, VEGFR and TGFb signaling. Hence, this review was conducted to review an updated view of the role of miRNAs in GC pathogenesis and their modulatory effects on responses to different GC treatment modalities.
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9
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Li M, Li Z, Wang P, Ma Q. A novel bimetallic MXene derivative QD-based ECL sensor for miRNA-27a-3p detection. Biosens Bioelectron 2023; 228:115225. [PMID: 36924689 DOI: 10.1016/j.bios.2023.115225] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Revised: 03/01/2023] [Accepted: 03/10/2023] [Indexed: 03/13/2023]
Abstract
In this work, a novel ECL biosensor has been developed based on bimetallic MXene derivative QDs (Mo2TiC2 QDs) and SnS2 nanosheets/lipid bilayer to detect the gastric cancer marker miRNA-27a-3p. On the one hand, the inter-band excitation of Mo2TiC2 QDs can inject the additional carriers, which were less suppressed by boundary effects and made a significant contribution to the luminescence process. Semiconductor Mo2TiC2 further inhibited the formation of internal electric field and potential oxidation. Therefore, Mo2TiC2 QDs processed superior luminous intensity and better stability. On the other hand, SnS2 nanosheets coated with phospholipid bilayer were designed as sensing interface. SnS2 nanosheets not only enhanced the luminous intensity of Mo2TiC2 QDs by virtue of their large surface area and low dielectric constant, but also improved the stability of lipid bilayer. Due to the excellent properties and synergy work of Mo2TiC2 QDs and the lipid bilayer-modified SnS2 nanosheets, the sensing system displayed high sensitivity and good reproducibility in the analysis application. As a result, the biosensor displayed good linear correlation between the ECL intensity and the concentration of miRNA-27a-3p over a wide range from 1 fM to 10 nM with the detection limit as low as 1 fM. The sensing system including the joint contribution of Mo2TiC2 QDs, SnS2 nanosheets and lipid bilayers had great potential for clinical applications.
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Affiliation(s)
- Mingxuan Li
- Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun, 130012, China
| | - Zhenrun Li
- Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun, 130012, China
| | - Peilin Wang
- Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun, 130012, China
| | - Qiang Ma
- Department of Analytical Chemistry, College of Chemistry, Jilin University, Changchun, 130012, China.
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Shen X, Zhu X, Hu P, Ji T, Qin Y, Zhu J. Knockdown circZNF131 Inhibits Cell Progression and Glycolysis in Gastric Cancer Through miR-186-5p/PFKFB2 Axis. Biochem Genet 2022; 60:1567-1584. [PMID: 35059934 DOI: 10.1007/s10528-021-10165-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 12/06/2021] [Indexed: 11/02/2022]
Abstract
Gastric cancer (GC) is a prevalent and heterogeneous malignancy in the digestive system. Increasing studies have suggested that circular RNAs are implicated in GC pathogenesis. This study aimed to explore the biological role and underlying mechanism of circRNA zinc finger protein 131 (circZNF131) in GC. The expression pattern of circZNF131, microRNA-186-5p (miR-186-5p), and 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 (PFKFB2) mRNA in GC tissues and cells was detected by quantitative real-time polymerase chain reaction. The stability of circZNF131 was verified using ribonuclease R assay. Functional experiments were performed by colony formation assay for cloning ability analysis, transwell assay and wounding healing assay for cell metastasis, and flow cytometry for cell apoptosis. Glycolysis metabolism was investigated by determining the levels of glucose uptake and lactate production. The protein detection of apoptosis- or glycolysis-associated markers, PFKFB2, and Ki-67 was implemented by western blot or immunohistochemistry. Dual-luciferase reporter assay was conducted to identify the interaction between miR-186-5p and circZNF131 or PFKFB2. The role of circZNF131 on tumor growth in nude mice was investigated via xenograft tumor assay. Expression analysis indicated that circZNF131 was upregulated in GC tissues and cells in a stable structure. Functional analyses showed that circZNF131 knockdown suppressed GC cell colony formation ability, migration, invasion and glycolysis metabolism, and induced cell apoptosis. Mechanically, miR-186-5p was a target of circZNF131, and miR-186-5p could bind to PFKFB2. Rescue experiments presented that miR-186-5p inhibition reversed the effects of circZNF131 knockdown on GC cell growth and glycolysis, and PFKFB2 overexpression abolished the impacts of miR-186-5p restoration on GC cell progression. Moreover, circZNF131 could positively modulate PFKFB2 expression via sponging miR-186-5p. In vivo, circZNF131 knockdown hindered GC tumor growth by regulating the miR-186-5p/PFKFB2 axis. circZNF131 could exert an oncogenic role in GC malignant development through the miR-186-5p/PFKFB2 axis, which might provide novel targets for GC treatment.
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Affiliation(s)
- Xingjie Shen
- Department of Gastroenterology, Jinan Central Hospital Affiliated to Shandong First Medical University, No.105 Jiefang Road, Lixia District, Jinan City, 250013, Shandong Province, China.
| | - Xiaoyan Zhu
- Department of Gastroenterology, Jinan Central Hospital Affiliated to Shandong First Medical University, No.105 Jiefang Road, Lixia District, Jinan City, 250013, Shandong Province, China
| | - Peixin Hu
- Department of Gastroenterology, Jinan Central Hospital Affiliated to Shandong First Medical University, No.105 Jiefang Road, Lixia District, Jinan City, 250013, Shandong Province, China
| | - Tingting Ji
- Department of Gastroenterology, Jinan Central Hospital Affiliated to Shandong First Medical University, No.105 Jiefang Road, Lixia District, Jinan City, 250013, Shandong Province, China
| | - Ying Qin
- Department of Gastroenterology, Jinan Central Hospital Affiliated to Shandong First Medical University, No.105 Jiefang Road, Lixia District, Jinan City, 250013, Shandong Province, China
| | - Jingyu Zhu
- Department of Gastroenterology, Jinan Central Hospital Affiliated to Shandong First Medical University, No.105 Jiefang Road, Lixia District, Jinan City, 250013, Shandong Province, China
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11
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Yu ZH, Cao M, Wang YX, Yan SY, Qing LT, Wu CM, Li S, Li TY, Chen Q, Zhao J. Urolithin A Attenuates Helicobacter pylori-Induced Damage In Vivo. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:11981-11993. [PMID: 36106620 DOI: 10.1021/acs.jafc.2c03711] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Urolithin A (UA) is a metabolite produced in the gut following the consumption of ellagic acid (EA) rich foods. EA has shown anti-inflammatory, antioxidant, and anticancer properties. Because EA is poorly absorbed in the gastrointestinal tract, urolithins are considered to play a major role in bioactivity. Helicobacter pylori (H. pylori) infection is the most common chronic bacterial infection all over the world. It is potentially hazardous to humans because of its relationship to various gastrointestinal diseases. In this study, we investigated the effect of UA on inflammation by H. pylori. The results indicated that UA attenuated H. pylori-induced inflammation in vitro and in vivo. UA also reduced the secretion of H. pylori virulence factors and tissue injuries in mice. Furthermore, UA decreased the relative abundance of Helicobacteraceae in feces of H. pylori-infected mice. In summary, taking UA effectively inhibited the injury caused by H. pylori.
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Affiliation(s)
- Zhi-Hao Yu
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610065, China
| | - Mei Cao
- Core Laboratory, School of Medicine, Sichuan Provincial People's Hospital Affiliated to University of Electronic Science and Technology of China, Chengdu 610072, China
| | - Yuan-Xiao Wang
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610065, China
| | - Shi-Ying Yan
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610065, China
| | - Li-Ting Qing
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610065, China
| | - Cheng-Meng Wu
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610065, China
| | - Shu Li
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610065, China
| | - Tian-Yi Li
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610065, China
| | - Qian Chen
- Irradiation Preservation Technology Key Laboratory of Sichuan Province, Sichuan Institute of Atomic Energy, Chengdu 610101, China
| | - Jian Zhao
- Key Laboratory of Biological Resource and Ecological Environment of Chinese Education Ministry, College of Life Sciences, Sichuan University, Chengdu 610065, China
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12
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Li B, Liang L, Chen Y, Liu J, Wang Z, Mao Y, Zhao K, Chen J. Circ_0008287 promotes immune escape of gastric cancer cells through impairing microRNA-548c-3p-dependent inhibition of CLIC1. Int Immunopharmacol 2022; 111:108918. [PMID: 35905561 DOI: 10.1016/j.intimp.2022.108918] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 05/23/2022] [Accepted: 05/30/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Analyses in silico suggested the upregulation of a circular RNA (circRNA), circ_0008287, in gastric cancer and possible interactions among microRNA (miR)-548c-3p, circ_0008287, and intracellular chloride channel protein 1 (CLIC1). This study aims to testify whether circ_0008287 can affect the immune escape of gastric cancer cells by regulating miR-548c-3p and CLIC1. METHODS RT-qPCR was performed to determine the expression pattern of circ_0008287 in gastric cancer cells. Gain- and loss-of function assays were then performed to assess the effects of circ_0008287 on malignant phenotypes of cancer cells. Interactions among circ_0008287, miR-548c-3p and CLIC1 were verified by dual luciferase reporter gene, RIP and FISH assays. Effects of CLIC1 on IFN-γ secretion and apoptosis in CD8 + T cells were evaluated by flow cytometry following co-culture of CD8 + T cells with cancer cells overexpressing/silencing CLIC1. A gastric cancer mouse model was further developed for in vivo investigation on effects of circ_0008287 on tumorigenesis and tumor metastasis. RESULTS circ_0008287, an upregulated circRNA in gastric cancer cells, augmented the viability as well as invasive and migratory potentials of gastric cancer cells. By competitively binding to miR-548c-3, circ_0008287 increased the expression of CLIC1, which impaired the function of CD8 + T cells and promoted their apoptosis. After downregulation of circ_0008287, in vivo tumorigenesis and metastasis were suppressed. CONCLUSION Hence, this study suggests the promotive role of circ_0008287 in gastric cancer progression and immune escape and further elucidates the underlying circ_0008287/miR-548c-3p/CLIC1 regulatory axis.
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Affiliation(s)
- Bopei Li
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, P.R. China; Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, P.R. China
| | - Liang Liang
- Department of General Surgery, the Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, P.R. China
| | - Yeyang Chen
- Departments of Gastrointestinal Surgery, The First People's Hospital of Yulin, Yulin 537000, P.R. China
| | - Jinlu Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, P.R. China
| | - Zhen Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, P.R. China
| | - Yuantian Mao
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, P.R. China
| | - Kun Zhao
- Departments of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, P.R. China
| | - Junqiang Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, P.R. China; Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, Nanning 530021, P.R. China.
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13
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Ju Y, Seol YM, Kim J, Jin H, Choi GE, Jang A. Expression Profiles of Circulating MicroRNAs in XELOX-Chemotherapy-Induced Peripheral Neuropathy in Patients with Advanced Gastric Cancer. Int J Mol Sci 2022; 23:ijms23116041. [PMID: 35682716 PMCID: PMC9180980 DOI: 10.3390/ijms23116041] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Revised: 05/24/2022] [Accepted: 05/25/2022] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer (GC) is one of the most common cancers and a leading cause of cancer deaths around the world. Chemotherapy is one of the most effective treatments for cancer patients, and has remarkably enhanced survival rates. However, it has many side effects. Recently, microRNAs (miRNAs) have been intensively studied as potential biomarkers for cancer diagnosis and treatment monitoring. However, definitive biomarkers in chemotherapy-induced peripheral neuropathy (CIPN) are still lacking. The aim of this study was to identify the factors significant for neurological adverse events in GC patients receiving XELOX (oxaliplatin and capecitabine) chemotherapy. The results show that XELOX chemotherapy induces changes in the expression of hsa-miR-200c-3p, hsa-miR-885-5p, and hsa-miR-378f. Validation by qRT-PCR demonstrated that hsa-miR-378f was significantly downregulated in CIPN. Hsa-miR-378f was identified as showing a statistically significant correlation in GC patients receiving XELOX chemotherapy according to the analysis of differentially expressed (DE) miRNAs. Furthermore, 34 potential target genes were predicted using a web-based database for miRNA target prognostication and functional annotations. The identified genes are related to the peptidyl-serine phosphorylation and regulation of alternative mRNA splicing with enrichment in the gastric cancer, neurotrophin, MAPK, and AMPK signaling pathways. Collectively, these results provide information useful for developing promising strategies for the treatment of XELOX-chemotherapy-induced peripheral neuropathy.
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Affiliation(s)
- Yeongdon Ju
- Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Korea; (Y.J.); (J.K.); (H.J.)
- Clinical Trial Specialist Program for In Vitro Diagnostics, Brain Busan 21 Plus Program, Graduate School, Catholic University of Pusan, Busan 46252, Korea
| | - Young Mi Seol
- Division of Hematology-Oncology, Department of Internal Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Korea;
| | - Jungho Kim
- Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Korea; (Y.J.); (J.K.); (H.J.)
| | - Hyunwoo Jin
- Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Korea; (Y.J.); (J.K.); (H.J.)
- Clinical Trial Specialist Program for In Vitro Diagnostics, Brain Busan 21 Plus Program, Graduate School, Catholic University of Pusan, Busan 46252, Korea
| | - Go-Eun Choi
- Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Korea; (Y.J.); (J.K.); (H.J.)
- Correspondence: (G.-E.C.); (A.J.); Tel.: +82-51-510-0563 (G.-E.C.); +82-52-259-1252 (A.J.)
| | - Aelee Jang
- Department of Nursing, University of Ulsan, Ulsan 44610, Korea
- Correspondence: (G.-E.C.); (A.J.); Tel.: +82-51-510-0563 (G.-E.C.); +82-52-259-1252 (A.J.)
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14
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Xu Y, Wang G, Hu W, He S, Li D, Chen P, Zhang J, Gao Y, Yu D, Zong L. Clinical role of miR-421 as a novel biomarker in diagnosis of gastric cancer patients: A meta-analysis. Medicine (Baltimore) 2022; 101:e29242. [PMID: 35583533 PMCID: PMC9276225 DOI: 10.1097/md.0000000000029242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 04/18/2022] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) has been identified as one of the most common malignancies. It was found that microRNAs can be used as potential biomarkers for GC diagnosis. The aim of this study was to estimate the diagnostic value of 4 potential microRNAs in GC. METHODS PubMed, Embase, Cochrane Library, and Web of Science were used to search published studies. The quality of the studies was scored with the Quality Assessment of Diagnostic Accuracy Studies. The pooled sensitivity and specificity, diagnostic odds ratio (DOR) and area under the curve (AUC) were calculated. The heterogeneity was evaluated using Cochrane Q statistics and the inconsistency index. RESULTS A total of 22 studies reporting the diagnostic value of miR-21 (n = 9), miR-106 (n = 10), miR-421 (n = 5) and miR-223 (n = 3) were included. Quality Assessment of Diagnostic Accuracy Studies scores showed the high quality of the selected 22 articles. The random effects model was adopted by evaluating the heterogeneity between articles. The DOR, AUC, and Q value of miRNA-21 were 12.37 (95% confidence interval [CI]: 5.36-28.54), 0.86 and 0.79, respectively. The DOR, AUC and Q value of miRNA-106 were 12.98 [95% CI: 7.14-23.61], 0.85 and 0.78, respectively. The DOR, AUC and Q value of miRNA-421 were 27.86 [95% CI: 6.04-128.48], 0.92 and 0.86, respectively. The DOR, AUC and Q value of miRNA-223 were 18.50 [95% CI: 7.80-43.86], 0.87 and 0.80, respectively. These results indicate that miRNA-421 has the highest diagnostic accuracy, followed by miR-223, miRNA-21, and miRNA-106 among the 4 microRNAs in GC. CONCLUSIONS miR-21, miR-106, miR-421, and miR-223 have good diagnostic efficacy, especially miR-421, could be used as auxiliary diagnostic indicator for GC.
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Affiliation(s)
- Yingying Xu
- Department of General Surgery, Yizheng People's Hospital, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Guiping Wang
- Department of Gastrointestinal Surgery, Clinical Medical School of Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, PR China
- Clinical Medical College, Dalian Medical University, Liaoning, PR China
| | - Wenqing Hu
- Department of Gastrointestinal Surgery, Changzhi People's Hospital, The Affiliated Hospital of Shanxi Medical University, Changzhi, Shanxi, PR China
| | - Songbing He
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, PR China
| | - Dandan Li
- Department of Gastrointestinal Surgery, Changzhi People's Hospital, The Affiliated Hospital of Shanxi Medical University, Changzhi, Shanxi, PR China
| | - Ping Chen
- Department of Gastrointestinal Surgery, Clinical Medical School of Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, PR China
| | - Jinjie Zhang
- Department of Gastrointestinal Surgery, The Affiliated Heji Hospital of Changzhi Medical college, Changzhi, Shanxi, PR China
| | - Yongshun Gao
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China
| | - Duonan Yu
- Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Yangzhou University School of Medicine, Yangzhou, PR China
| | - Liang Zong
- Department of General Surgery, Yizheng People's Hospital, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
- Department of Gastrointestinal Surgery, Changzhi People's Hospital, The Affiliated Hospital of Shanxi Medical University, Changzhi, Shanxi, PR China
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15
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Huangfu L, Fan B, Wang G, Gan X, Tian S, He Q, Yao Q, Shi J, Li X, Du H, Gao X, Xing X, Ji J. Novel prognostic marker LINC00205 promotes tumorigenesis and metastasis by competitively suppressing miRNA-26a in gastric cancer. Cell Death Dis 2022; 8:5. [PMID: 35013132 PMCID: PMC8748761 DOI: 10.1038/s41420-021-00802-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 11/25/2021] [Accepted: 12/14/2021] [Indexed: 12/03/2022]
Abstract
Rapid proliferation and metastasis of gastric cancer (GC) resulted in a poor prognosis in the clinic. Previous studies elucidated that long non-coding RNA (LncRNA) LINC00205 was upregulated in various tumors and participated in tumor progression. The aim of our study was to investigate the regulating role of LINC00205 in tumorigenesis and metastasis of GC. Both public datasets and our data showed that the LINC00205 was highly expressed in GC tissues and several cell lines. Notably, GC patients with high level of LINC00205 had a poor prognosis in our cohort. Mechanistically, knockdown of LINC00205 by shRNAs suppressed GC cells proliferation, migration, invasion remarkably, and induced cell cycle arrest. Based on bioinformatics prediction, we found that LINC00205 might act as a competitive endogenous RNA (ceRNA) through targeting miR-26a. The level of miR-26a had negatively correlated with LINC00205 expression and was decreased among GC cell lines, tissues, and serum samples. Our results for the first time confirmed that miR-26a was a direct target of LINC00205 and might have the potential to become a plasma marker for clinical tumor diagnosis. Indeed, LINC00205 knockdown resulted in the dramatic promotion of miR-26a expression as well as inhibition of miR-26a potential downstream targets, such as HMGA2, EZH2, and USP15. These targets were essential for cell survival and epithelial-mesenchymal transition. Importantly, LINC00205 was able to remodel the miR-26a-mediated downstream silence, which identified a new mechanism of malignant transformation of GC cells. In conclusion, this study revealed the regulating role of the LINC00205/miR-26a axis in GC progression and provided a new potential therapeutic strategy for GC treatment.
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Affiliation(s)
- Longtao Huangfu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Fu-Cheng Road, Beijing, 100142, China
| | - Biao Fan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Fu-Cheng Road, Beijing, 100142, China
| | - Gangjian Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Fu-Cheng Road, Beijing, 100142, China.,Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Fu-Cheng Road, Beijing, 100142, China
| | - Xuejun Gan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Fu-Cheng Road, Beijing, 100142, China.,Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Fu-Cheng Road, Beijing, 100142, China
| | - Shanshan Tian
- National Institute on Drug Dependence, Peking University, North Huayuan Road, Beijing, 100191, China
| | - Qifei He
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Fu-Cheng Road, Beijing, 100142, China.,Department of Orthopedics, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, 518025, China
| | - Qian Yao
- Department of Pathology, Peking University Cancer Hospital & Institute, Fu-Cheng Road, Beijing, 100142, China
| | - Jinyao Shi
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Fu-Cheng Road, Beijing, 100142, China.,Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Fu-Cheng Road, Beijing, 100142, China
| | - Xiaomei Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Fu-Cheng Road, Beijing, 100142, China
| | - Hong Du
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Fu-Cheng Road, Beijing, 100142, China
| | - Xiangyu Gao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Fu-Cheng Road, Beijing, 100142, China
| | - Xiaofang Xing
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Fu-Cheng Road, Beijing, 100142, China.
| | - Jiafu Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Fu-Cheng Road, Beijing, 100142, China. .,Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Fu-Cheng Road, Beijing, 100142, China.
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16
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Ahmadi A, Bayatiani MR, Seif F, Ansari J, Rashidi P, Moghadasi M, Etemadi M. Evaluation of Radiotherapy on miR-374 Gene Expression in Colorectal Cancer Patient Blood Samples. Rep Biochem Mol Biol 2022; 10:614-621. [PMID: 35291612 PMCID: PMC8903365 DOI: 10.52547/rbmb.10.4.614] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 04/24/2021] [Indexed: 06/14/2023]
Abstract
BACKGROUND Current cancer treatments include surgery, radiotherapy, chemotherapy, and immunotherapy. Despite these treatments, a main issue in cancer treatment is early detection. microRNAs (miRNAs) can be used as markers to diagnose and treat cancers. This study investigated the effect of radiotherapy on miR-374 expression, and APC and GSK-3β, two of its target genes, in the WNT pathway, in peripheral blood samples from radiotherapy-treated colorectal cancer (CRC) patients. METHODS Peripheral blood was collected from 25 patients before and after radiotherapy. RNA was extracted from the blood and cDNA synthesized. miR-374, APC, and GSK-3β expression was determined by real-time polymerase chain reaction (RT-PCR) and the amplicons were sequenced. Finally, the data were statistically evaluated. RESULTS Quantitative RT-PCR revealed significant down-regulation of miR-374 (0.63-fold) and up-regulation of APC (1.12-fold) and GSK-3β (1.22-fold) in CRC patients after five weeks of radiotherapy. Sequencing of PCR-produced amplicons confirmed the conservation of mature and precursor sequences encoding miR-374. miR-374 expression changed with time after radiotherapy treatment and related tumor grading. Increased age and tumor grade positively correlated with decreased miR-374 expression. CONCLUSION miR-374 expression, and that of its two target genes, APC and GSK-3β, changed after radiotherapy. These genes can likely be used as diagnostic radiotherapy markers in CRC.
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Affiliation(s)
- Azam Ahmadi
- Infectious Diseases Research Center (IDRC), Arak University of Medical Sciences, Arak, Iran.
| | - Mohammad Reza Bayatiani
- Department of Medical Physics and Radiotherapy, Arak University of Medical Sciences and Khansari Hospital, Arak, Iran.
| | - Fatemeh Seif
- Department of Medical Physics and Radiotherapy, Arak University of Medical Sciences and Khansari Hospital, Arak, Iran.
| | - Jamshid Ansari
- Department of Medical Physics and Radiotherapy, Arak University of Medical Sciences and Khansari Hospital, Arak, Iran.
| | - Parisa Rashidi
- Department of Medical Physics and Radiotherapy, Arak University of Medical Sciences and Khansari Hospital, Arak, Iran.
| | - Mona Moghadasi
- Students Research Committee, Arak University of Medical Sciences, Arak, Iran.
| | - Mobarakeh Etemadi
- Students Research Committee, Arak University of Medical Sciences, Arak, Iran.
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17
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Han S, Tay JK, Loh CJL, Chu AJM, Yeong JPS, Lim CM, Toh HC. Epstein–Barr Virus Epithelial Cancers—A Comprehensive Understanding to Drive Novel Therapies. Front Immunol 2021; 12:734293. [PMID: 34956172 PMCID: PMC8702733 DOI: 10.3389/fimmu.2021.734293] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 11/12/2021] [Indexed: 12/19/2022] Open
Abstract
Epstein–Barr virus (EBV) is a ubiquitous oncovirus associated with specific epithelial and lymphoid cancers. Among the epithelial cancers, nasopharyngeal carcinoma (NPC), lymphoepithelioma-like carcinoma (LELC), and EBV-associated gastric cancers (EBVaGC) are the most common. The role of EBV in the pathogenesis of NPC and in the modulation of its tumour immune microenvironment (TIME) has been increasingly well described. Much less is known about the pathogenesis and tumour–microenvironment interactions in other EBV-associated epithelial cancers. Despite the expression of EBV-related viral oncoproteins and a generally immune-inflamed cancer subtype, EBV-associated epithelial cancers have limited systemic therapeutic options beyond conventional chemotherapy. Immune checkpoint inhibitors are effective only in a minority of these patients and even less efficacious with molecular targeting drugs. Here, we examine the key similarities and differences of NPC, LELC, and EBVaGC and comprehensively describe the clinical, pathological, and molecular characteristics of these cancers. A deeper comparative understanding of these EBV-driven cancers can potentially uncover targets in the tumour, TIME, and stroma, which may guide future drug development and cast light on resistance to immunotherapy.
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Affiliation(s)
- Shuting Han
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Joshua K. Tay
- Department of Otolaryngology—Head & Neck Surgery, National University of Singapore, Singapore, Singapore
| | | | | | - Joe Poh Sheng Yeong
- Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore
| | - Chwee Ming Lim
- Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore
| | - Han Chong Toh
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- *Correspondence: Han Chong Toh,
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18
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Choi JM, Kim SG. Effect of Helicobacter pylori Eradication on Epigenetic Changes in Gastric Cancer-related Genes. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2021. [DOI: 10.7704/kjhugr.2021.0042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
It is known that gastric carcinogenesis results from the progressive changes from chronic gastritis to gastric atrophy, intestinal metaplasia, dysplasia, and invasive carcinoma. Several genetic and epigenetic alterations are involved in this process, and Helicobacter pylori (H. pylori) infection is believed to induce the initiation and progression of these steps. From an epigenetic point of view, H. pylori induces hypermethylation of genes involved in the development of gastric cancer and regulates the expression of various microRNAs (miRNAs). These H. pylori-related epigenetic changes are accumulated not only at the site of neoplasm but also in the adjacent non-cancerous gastric mucosa. Thereby, a state vulnerable to gastric cancer known as an epigenetic field defect is formed. H. pylori eradication can have an effective chemopreventive effect in gastric carcinogenesis. However, the molecular biological changes that occur in the stomach environment during H. pylori eradication have not yet been established. Several studies have reported that H. pylori eradication can restore infection-related changes, especially epigenetic alterations in gastric cancer-related genes, but some studies have shown otherwise. Simply put, it appears that the recovery of methylated gastric cancer-related genes and miRNAs during H. pylori eradication may vary among genes and may also differ depending on the histological subtype of the gastric mucosa. In this review, we will discuss the potential mechanism of gastric cancer prevention by H. pylori eradication, mainly from an epigenetic perspective.
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19
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Khayam N, Nejad HR, Ashrafi F, Abolhassani M. Expression Profile of miRNA-17-3p and miRNA-17-5p Genes in Gastric Cancer Patients with Helicobacter pylori Infection. J Gastrointest Cancer 2021; 52:130-137. [PMID: 31997281 DOI: 10.1007/s12029-019-00319-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND The most common chronic bacterial infection is Helicobacter pylori. The connection between chronic H. pylori infection and gastric cancer is recognized. The early detection of gastric cancer improves survival. miRNAs regulate gene expression in eukaryotes by inhibiting mRNA translocation or degradation. The objective of this study was to compare the expression of miRNA-17-3p and miRNA-17-5p genes in gastric cancer patients with Helicobacter pylori infection. METHODS Herein, 30 isolates were identified as H. pylori based on urease test, and 30 and 12 cases were isolated from gastric cancer patients and non-Helicobacter pylori cases as control, respectively. A peripheral blood sample was collected from patients. Analysis of total mRNA extracts from peripheral blood samples, for gene expression changes (miRNA-17-3p and miRNA-17-5p) by quantitative real-time polymerase chain reaction (qRT-PCR), was done. RESULTS As said by the results, p values showed that expression levels of miRNA-17-3p and miRNA-17-5p were significantly higher in H. pylori-positive GC patients and H. pylori-positive non-GC patients with comparing by healthy controls. So, there was no significant difference between expression levels of miRNA-17-3p and miRNA-17-5p in H. pylori-positive GC patients and H. pylori-positive non-GC patients. CONCLUSION Considering our results, the high expression of miRNA-17-3p and miRNA-17-5p has a direct relationship with increased cell proliferation, inhibition of tumor cell apoptosis and tumor angiogenesis, in addition to miRNAs play an important role as biomarkers in helping for detection of the patient by H. pylori infection to become cancerous. Therefore, it can be used to make specific diagnostic kits and to treat patients.
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Affiliation(s)
- Nazanin Khayam
- Faculty of Biological Sciences, Islamic Azad University, North Tehran Branch, Tehran, Iran
| | - Hamideh Rouhani Nejad
- Department of Microbiology, Islamic Azad University, North Tehran Branch, Tehran, Iran.
| | - Fatemeh Ashrafi
- Department of Microbiology, Islamic Azad University, North Tehran Branch, Tehran, Iran
| | - Mohsen Abolhassani
- Hybridoma Lab., Dept. of Immunology, Pasteur Institute of Iran, Tehran, 13164, Iran
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20
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Dong W, Li J, Dong X, Shi W, Zhang Y, Liu Y. MiR-17 and miR-93 Promote Tumor Progression by Targeting p21 in Patients with Chordoma. Onco Targets Ther 2021; 14:3109-3118. [PMID: 34054299 PMCID: PMC8153071 DOI: 10.2147/ott.s307138] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 04/16/2021] [Indexed: 12/14/2022] Open
Abstract
Objective MicroRNAs have been implicated in the progression of various cancers. However, the role of microRNAs in chordoma remains to be further elucidated. Here, we purposed to character the role of two microRNAs, miR-17 and miR-93, and their potential mechanisms in chordoma. Methods The expression and prognostic value of miR-17 and miR-93 were assessed by the quantitative real-time polymerase chain reaction, Kaplan-Meier survival curve, and Cox regression analysis. The effects of miR-17/93 mimics on chordoma cell proliferation, colony formation, and invasion were analyzed by CCK-8 assay, colony formation assay, and transwell assay. The downstream target of miR-17/93 was further explored via luciferase reporter assay. Results High expression of miR-17/93 was identified in chordoma tissues, and was associated with poor prognosis. Overexpression of miR-17/93 contributed to cell proliferation, colony formation, and invasion. Mechanistically, we demonstrated that miR-17/93 directly targeted p21 and decreased the expression of p21. Besides, the rescue assay further confirmed the essential role of the miR-17/93-p21 axis in chordoma. Conclusion Our results revealed the potential oncogenic effect of the miR-17/93 on chordoma progression, and suggested that the miR-17/93-p21 axis served as a promising therapeutic target in chordoma.
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Affiliation(s)
- Wei Dong
- Department of Neurosurgery, Tangshan People's Hospital, Tangshan, Hebei, People's Republic of China
| | - Jingwu Li
- Department of Tumor Surgery, Tangshan People's Hospital, Tangshan, Hebei, People's Republic of China
| | - Xiaoliu Dong
- Department of Neurology, Tangshan People's Hospital, Tangshan, Hebei, People's Republic of China
| | - Wenjian Shi
- Department of Neurosurgery, Tangshan People's Hospital, Tangshan, Hebei, People's Republic of China
| | - Yu Zhang
- Department of Neurological Intensive Care Unit, Tangshan People's Hospital, Tangshan, Hebei, People's Republic of China
| | - Yongliang Liu
- Department of Neurosurgery, Tangshan People's Hospital, Tangshan, Hebei, People's Republic of China
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Wang D, Sang Y, Sun T, Kong P, Zhang L, Dai Y, Cao Y, Tao Z, Liu W. Emerging roles and mechanisms of microRNA‑222‑3p in human cancer (Review). Int J Oncol 2021; 58:20. [PMID: 33760107 PMCID: PMC7979259 DOI: 10.3892/ijo.2021.5200] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 01/12/2021] [Indexed: 12/17/2022] Open
Abstract
MicroRNAs (miRNAs/miRs) are a class of small non‑coding RNAs that maintain the precise balance of various physiological processes through regulating the function of target mRNAs. Dysregulation of miRNAs is closely associated with various types of human cancer. miR‑222‑3p is considered a canonical factor affecting the expression and signal transduction of multiple genes involved in tumor occurrence and progression. miR‑222‑3p in human biofluids, such as urine and plasma, may be a potential biomarker for the early diagnosis of tumors. In addition, miR‑222‑3p acts as a prognostic factor for the survival of patients with cancer. The present review first summarizes and discusses the role of miR‑222‑3p as a biomarker for diverse types of cancers, and then focuses on its essential roles in tumorigenesis, progression, metastasis and chemoresistance. Finally, the current understanding of the regulatory mechanisms of miR‑222‑3p at the molecular level are summarized. Overall, the current evidence highlights the crucial role of miR‑222‑3p in cancer diagnosis, prognosis and treatment.
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Affiliation(s)
| | | | | | - Piaoping Kong
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
| | - Lingyu Zhang
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
| | - Yibei Dai
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
| | - Ying Cao
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
| | - Zhihua Tao
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
| | - Weiwei Liu
- Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
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22
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Sun W, Jiang C, Ji Y, Xiao C, Song H. Long Noncoding RNAs: New Regulators of Resistance to Systemic Therapies for Gastric Cancer. BIOMED RESEARCH INTERNATIONAL 2021; 2021:8853269. [PMID: 33506041 PMCID: PMC7808844 DOI: 10.1155/2021/8853269] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 12/07/2020] [Accepted: 12/19/2020] [Indexed: 02/07/2023]
Abstract
Gastric cancer (GC) is the second leading cause of cancer mortality and the fourth most commonly diagnosed malignant disease, with approximately 951,000 new cases diagnosed and approximately 723,000 cases of mortality each year. The highest mortality rate of GC is in East Asia, and the lowest is in North America. A large number of studies have demonstrated that GC patients are characterized by higher morbidity, metastasis rates, and mortality and lower early diagnosis rates, radical resection rates, and 5-year survival rates. All cases of GC can be divided into two important stages, namely, early- and advanced-stage GC, and the stage mainly determines the treatment strategy for and the therapeutic effect in GC patients. Patients with early-stage GC undergo radical surgery followed by chemotherapy, and the 5-year survival rate can be as high as 90%. However, patients with advanced-stage GC cannot undergo radical surgery because they are at risk for metastasis; therefore, they can choose only radiotherapy or chemotherapy and have a poor prognosis. Based on the lack of specific clinical manifestations and detection methods, most GC patients (>70%) are diagnosed in the advanced stage; therefore, continued efforts toward developing treatments have been focused on advanced-stage GC patients and include molecular targeted therapy, immunotherapy, and small molecular therapy. Nevertheless, in recent years, accumulating evidence has indicated that small molecules, especially long noncoding RNAs (lncRNAs), are involved in the occurrence, development, and progression of GC, and their abundantly dysregulated expression has been identified in GC tissues and cell lines. Therefore, lncRNAs are considered easily detectable molecules and ideal biomarkers or target-specific agents for the future diagnosis or treatment of GC. In this review, we primarily discuss the status of GC, the role of lncRNAs in GC, and the emerging systemic treatments for GC.
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Affiliation(s)
- Weihong Sun
- Department of Internal Medicine-Oncology Affiliated Qingdao Central Hospital, Qingdao University, 127 Siliu South Road, Qingdao 266042, China
- Department of Internal Medicine-Oncology Qingdao Tumor Hospital, 127 Siliu South Road, Qingdao 266042, China
| | - Changqing Jiang
- Department of Pathology Qingdao Municipal Hospital, Donghai Middle Road, Qingdao 266071, China
| | - Ying Ji
- Department of Internal Medicine-Oncology Affiliated Qingdao Central Hospital, Qingdao University, 127 Siliu South Road, Qingdao 266042, China
- Department of Internal Medicine-Oncology Qingdao Tumor Hospital, 127 Siliu South Road, Qingdao 266042, China
| | - Chao Xiao
- Department of Internal Medicine-Oncology Affiliated Qingdao Central Hospital, Qingdao University, 127 Siliu South Road, Qingdao 266042, China
- Department of Internal Medicine-Oncology Qingdao Tumor Hospital, 127 Siliu South Road, Qingdao 266042, China
| | - Haiping Song
- Department of Internal Medicine-Oncology Affiliated Qingdao Central Hospital, Qingdao University, 127 Siliu South Road, Qingdao 266042, China
- Department of Internal Medicine-Oncology Qingdao Tumor Hospital, 127 Siliu South Road, Qingdao 266042, China
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Bayatiani MR, Ahmadi A, Aghabozorgi R, Seif F. Concomitant Up-Regulation of Hsa- Mir-374 and Down-Regulation of Its Targets, GSK-3β and APC, in Tissue Samples of Colorectal Cancer. Rep Biochem Mol Biol 2021; 9:408-416. [PMID: 33969134 PMCID: PMC8068448 DOI: 10.52547/rbmb.9.4.408] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Accepted: 06/28/2020] [Indexed: 12/31/2022]
Abstract
BACKGROUND The WNT-pathway is involved in several cancers, including colorectal cancer (CRC). Many cell signaling components and pathways are controlled by microRNAs. The main purpose of the present study was to investigate the expression of hsa-miR-374, and its two target genes of the Wnt-pathway in CRC clinical samples. METHODS In this study, we predicted the miRNAs targeting key genes of WNT-pathway using bioinformatics algorithms. The expression levels of hsa-miR-374, APC and GSK-3β on 48 pairs of Formalin-Fixed Paraffin-Embedded (FFPE) CRC tumors and marginal-tumors were evaluated using real time-PCR. Additionally, the hsa-miR-374a-5p precursor sequence was amplified by whole-blood DNA as a template. This amplicon was cloned into pEGFP-c1 expression vector and transfected into SW742 cells. Aside from this, MTT assay was performed to evaluate the effect of miR-374 on cell viability. RESULTS The bioinformatics analysis indicated that hsa-miR-374 binds to the regulatory region the key components of WNT-pathway, including APC and GSK-3β considering the recognition elements and mirSVR scores. Our results revealed significant down-regulation of GSK-3β (0.94 times, p= 0.0098) and APC (0.96 times, p= 0.03) and up-regulation of miR-374 (1.22 times, p= 0.0071) on tumor samples compared with their normal pairs. Meanwhile, the results of the over-expression of miR-374 showed down-regulation of APC and GSK-3β. MTT-assay also indicated that the miR-374 increased cell survival. CONCLUSION The results of our study indicated a concomitant change in the expression of miR-374 and its two related target genes, in clinical samples of CRC. Hsa-miR-374 might be as a helpful biomarker or therapeutic target in CRC.
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Affiliation(s)
- Mohammad Reza Bayatiani
- Department of Radiotherapy and Medical Physics, Arak University of Medical Sciences, Arak, Iran.
| | - Azam Ahmadi
- Infectious Diseases Research Center (IDRC), Arak University of Medical Sciences, Arak, Iran.
| | - Reza Aghabozorgi
- Khansari Hospital and Department of Internal Medicine, School of Medicine, Arak University of Medical Sciences, Arak, Iran.
| | - Fatemeh Seif
- Department of Radiotherapy and Medical Physics, Arak University of Medical Sciences, Arak, Iran.
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Chen J, Wu L, Sun Y, Luo C, Chen X, Wu L, Ding J, Pan G, Han C, Wu Z, Shen Y. Diagnostic value and clinical significance of circulating miR-650 and CA211 in detecting of gastric carcinoma. Oncol Lett 2020; 20:254. [PMID: 32994817 PMCID: PMC7509765 DOI: 10.3892/ol.2020.12117] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 08/25/2020] [Indexed: 12/15/2022] Open
Abstract
The present study determined the levels of plasma biomarkers in patients with gastric carcinoma (GC) and investigated their clinical significance and diagnostic value. Between April 2014 and December 2018, 90 patients with GC, 90 patients with precancerous lesions (Pre) and 45 healthy controls (NC) were recruited from the Affiliated Liutie Central Hospital of Guangxi Medical University. Five markers were measured: microRNA-650 (miRNA-650; using reverse transcription-quantitative polymerase chain reaction), and carcinoembryonic antigen (CEA), carbohydrate antigen (CA)125, CA211 and CA50 using electrochemiluminescence. Circulating markers were all upregulated in patients with GC (P<0.05), and CA211 and CA50 were significantly increased in patients with Pre. The miRNA-650 and CA211 had an area under the curve (AUC) of 0.700 (moderate) and 0.866 (high), respectively, in the diagnosis of GC. Differentiation of GC from Pre yielded an AUC of 0.665 (low) and 0.708 (moderate), respectively. The combination model of miRNA-650 and CA211 showed an appropriate value of AUC (0.887) to discriminate the GC patients from the healthy subjects with a sensitivity and specificity of 82.5 and 97.7%. Additionally, differentiating GC from Pre yielded an AUC of 0.767 with a sensitivity of 57.1% and a specificity of 95%, respectively. In terms of clinicopathological features, the expression of miRNA-650 and CA211 in plasma was not associated with the patients' age, sex, Tumor-Node-Metastasis stage, or histological type. In conclusion, plasma miRNA-650 and CA211 is a promising and powerful non-invasive marker for the detection of GC.
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Affiliation(s)
- Jianlin Chen
- Department of Clinical Laboratory, Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou, Guangxi 545007, P.R. China
| | - Lihua Wu
- Department of Digestive Internal Medicine, Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou, Guangxi 545007, P.R. China
| | - Yifan Sun
- Department of Clinical Laboratory, Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou, Guangxi 545007, P.R. China
| | - Changjun Luo
- Department of Internal Medicine-Cardiovascular, Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou, Guangxi 545007, P.R. China
| | - Xianhua Chen
- Department of Clinical Laboratory, Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou, Guangxi 545007, P.R. China
| | - Lihong Wu
- Department of Clinical Laboratory, Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou, Guangxi 545007, P.R. China
| | - Junping Ding
- Department of Urinary Surgery, Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou, Guangxi 545007, P.R. China
| | - Gangxi Pan
- Department of Clinical Laboratory, Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou, Guangxi 545007, P.R. China
| | - Chaowen Han
- Department of Oncology, Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou, Guangxi 545007, P.R. China
| | - Zijuan Wu
- Department of Clinical Laboratory, Rongshui Miao Autonomous County People's Hospital, Liuzhou, Guangxi 545000, P.R. China
| | - Yongqi Shen
- Department of Oncology, Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou, Guangxi 545007, P.R. China
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25
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MicroRNA-1297 inhibits proliferation and promotes apoptosis in gastric cancer cells by downregulating CDC6 expression. Anticancer Drugs 2020; 30:803-811. [PMID: 31419217 DOI: 10.1097/cad.0000000000000776] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Gastric cancer (GC), one of the most common malignant tumors and the second most common leading cause of cancer-related death worldwide, is a biologically heterogeneous disease accompanied by various genetic and epigenetic alterations. However, the molecular mechanisms underlying this disease are complex and not completely understood. Increasing studies have shown that aberrant microRNA (miRNA) expression is associated with GC tumorigenesis and growth. MiR-1297 has been confirmed to be a cancer suppressor in diverse tumors in humans. However, to date, the function and mechanism of miR-1297 in GC have not been determined. Here, we found that the expression of miR-1297 was significantly reduced in GC tissues or GC cell lines compared with paracarcinoma normal tissue or normal cell lines. Exogenic overexpression of miR-1297 in GC cell lines can inhibit cell proliferation and colony formation and induce apoptosis, and inhibition of miR-1297 in GC cell lines can promote cell proliferation and colony formation, and reduce apoptosis in vitro. We further confirmed that miR-1297 acted as a tumor suppressor through targeting cell division control protein 6 (CDC6) in GC. Moreover, the inverse relationship between miR-1297 and CDC6 was verified in GC cell lines. Our results indicated that miR-1297 is a potent tumor suppressor in GC, and its antiproliferative and gene-regulatory effects are, in part, mediated through its downstream target gene, CDC6. These findings implied that miR-1297 might be used as a novel therapeutic target of GC.
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26
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Sexton RE, Hallak MNA, Uddin MH, Diab M, Azmi AS. Gastric Cancer Heterogeneity and Clinical Outcomes. Technol Cancer Res Treat 2020; 19:1533033820935477. [PMID: 32799763 PMCID: PMC7432987 DOI: 10.1177/1533033820935477] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Gastric adenocarcinoma is a highly aggressive disease with poor overall survival.
The aggressive nature of this disease is in part due to the high intra and inter
tumoral heterogeneity and also due to the late diagnosis at presentation. Once
progression occurs, treatment is more difficult due to the adaptation of tumors,
which acquires resistance to commonly used chemotherapeutics. In this report,
using publicly available data sets and pathway analysis, we highlight the vast
heterogeneity of gastric cancer by investigating genes found to be significantly
perturbed. We found several upregulated genes in the diffuse gastric cancer
subtypes share similarity to gastric cancer as a whole which can be explained by
the increase in this subtype of gastric cancer throughout the world. We report
significant downregulation of genes that are underrepresented within the
literature, such as ADH7, GCNT2, and
LIF1, while other genes have not been explored within
gastric cancer to the best of our knowledge such as METTL7A,
MAL, CWD43, and SLC2A12.
We identified gender to be another heterogeneous component of this disease and
suggested targeted treatment strategies specific to this heterogeneity. In this
study, we provide an in-depth exploration of the molecular landscape of gastric
cancer in order to shed light onto novel areas of gastric cancer research and
explore potential new therapeutic targets.
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Affiliation(s)
- Rachel E Sexton
- Department of Oncology, 12267Wayne State University School of Medicine, Detroit, MI, USA
| | | | - Md Hafiz Uddin
- Department of Oncology, 12267Wayne State University School of Medicine, Detroit, MI, USA
| | - Maria Diab
- Department of Oncology, 12267Wayne State University School of Medicine, Detroit, MI, USA
| | - Asfar S Azmi
- Department of Oncology, 12267Wayne State University School of Medicine, Detroit, MI, USA
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Yin G, Tian P, BuHe A, Yan W, Li T, Sun Z. LncRNA LINC00689 Promotes the Progression of Gastric Cancer Through Upregulation of ADAM9 by Sponging miR-526b-3p. Cancer Manag Res 2020; 12:4227-4239. [PMID: 32581594 PMCID: PMC7280092 DOI: 10.2147/cmar.s231042] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2019] [Accepted: 02/14/2020] [Indexed: 12/14/2022] Open
Abstract
Introduction Increasing studies have demonstrated that noncoding RNAs, including miRNAs and lncRNAs, have vital roles in mediating cancer progression. However, the expression features and biological functions of LINC00689 in gastric cancer (GC) remain largely unknown. This study was designed to investigate the functions of LINC00689, miR-526b-3p and ADAM9 as well as their interactions in GC. Methods Real time PCR(RT-PCR) was used to detect the expression of LINC0068, miR-526b-3p and ADAM9 in both GC tissues or cell lines. Gain- and loss- of functions of assays were conducted to verify the role of LINC0068, miR-526b-3p and ADAM9 in GC development. Cell proliferation were determined by CCK8 assay and transwell assay and scratch wound-healing assay were used to test cell invasion and migration. Further, the relationships between LINC00689 and miR-526b-3p, miR-526b-3p and ADAM9 were predicted by bioinformatics analysis and then proved by Luciferase reporter assay and RNA Immunoprecipitation(RIP) assay. Results We found that LINC00689 was upregulated in GC tissues and positively correlated with advanced tumor stage and tumor size, while miR-526b-3p was downregulated. Furthermore, gain- and loss-of-function experiments revealed that LINC00689 promoted the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of GC cells, while miR-526b-3p had the opposite effects. The underlying mechanisms indicated that LINC00689 functioned as a competing endogenous RNA (ceRNA) by sponging miR-526b-3p in GC cells. Further investigations confirmed that ADAM9 was a direct target of miR-526b-3p and positively modulated the progression of GC. Conclusion Our study suggests that LINC00689 functions as a novel oncogenic lncRNA in the development of GC by promoting ADAM9 expression through suppression of miR-526b-3p.
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Affiliation(s)
- Gang Yin
- Oncology Surgery Department, Beijing Shijitan Hospital, Capital Medical University (Peking University Ninth School of Clinical Medicine), Beijing 100038, People's Republic of China
| | - PeiRong Tian
- Oncology Surgery Department, Beijing Shijitan Hospital, Capital Medical University (Peking University Ninth School of Clinical Medicine), Beijing 100038, People's Republic of China
| | - Amin BuHe
- Oncology Surgery Department, Beijing Shijitan Hospital, Capital Medical University (Peking University Ninth School of Clinical Medicine), Beijing 100038, People's Republic of China
| | - Wei Yan
- Oncology Surgery Department, Beijing Shijitan Hospital, Capital Medical University (Peking University Ninth School of Clinical Medicine), Beijing 100038, People's Republic of China
| | - TianXiong Li
- Oncology Surgery Department, Beijing Shijitan Hospital, Capital Medical University (Peking University Ninth School of Clinical Medicine), Beijing 100038, People's Republic of China
| | - ZhiPeng Sun
- Oncology Surgery Department, Beijing Shijitan Hospital, Capital Medical University (Peking University Ninth School of Clinical Medicine), Beijing 100038, People's Republic of China
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28
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Qu X, Zhao L, Zhang R, Wei Q, Wang M. Differential microRNA expression profiles associated with microsatellite status reveal possible epigenetic regulation of microsatellite instability in gastric adenocarcinoma. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:484. [PMID: 32395528 PMCID: PMC7210178 DOI: 10.21037/atm.2020.03.54] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Background Although microsatellite instability (MSI) is a powerful predictive biomarker for the efficacy of immunotherapy, the mechanism of MSI in sporadic gastrointestinal cancer is not fully understood. However, epigenetics, particularly microRNAs, has been suggested as one of the main regulators that contribute to the MSI formation. Methods We used microRNA expression data of 386 gastric adenocarcinoma samples from The Cancer Genome Atlas (TCGA) database to identify differential microRNA expression profiles by different MSI status. We also obtained putative common target genes of the top differential microRNAs with miRanda online tools, and we analyzed these data by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment (KEGG). Results We found that 56 and 67 gastric adenocarcinoma samples were positive for low and high MSI, respectively, and that a high MSI status was associated with age, sex and subregion (P=0.049, 0.014 and 0.007, respectively). In the 67 samples with a high MSI status, expression levels of 14 microRNAs were upregulated but five microRNAs were downregulated as assessed by the fold change (FC), compared with that of the 56 samples with a low MSI status (P<0.05, |FC| >2). Further analysis suggested that the expression of miR-210-3p, miR-582-3p, miR-30a-3p and miR-105-5p predicted a high MSI status (P=4.93×10−10, 5.63×10−10, 3.23×10−9 and 7.64×10−4, respectively). Regulation of the transcription pathways ranked the top of lists from both GO and KEGG analyses, and these microRNAs might regulate DNA damage-repair genes that were also associated with a high MSI status. Conclusions MiR-30a-3p and miR-105-5p are potential biomarkers for the MSI-H gastric adenocarcinoma, possibly by altering expression of DNA damage-repair genes.
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Affiliation(s)
- Xiaofei Qu
- Cancer institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Liqin Zhao
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.,Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Ruoxin Zhang
- Cancer institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China.,Department of Epidemiology and Biostatistics, Fudan University School of Public Health, Shanghai 200032, China
| | - Qingyi Wei
- Cancer institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China.,Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.,Department of Population Health Sciences, Duke University School of Medicine, Durham, NC, USA
| | - Mengyun Wang
- Cancer institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
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Spaety ME, Gries A, Badie A, Venkatasamy A, Romain B, Orvain C, Yanagihara K, Okamoto K, Jung AC, Mellitzer G, Pfeffer S, Gaiddon C. HDAC4 Levels Control Sensibility toward Cisplatin in Gastric Cancer via the p53-p73/BIK Pathway. Cancers (Basel) 2019; 11:cancers11111747. [PMID: 31703394 PMCID: PMC6896094 DOI: 10.3390/cancers11111747] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 10/23/2019] [Accepted: 10/31/2019] [Indexed: 02/08/2023] Open
Abstract
Gastric cancer (GC) remains a health issue due to the low efficiency of therapies, such as cisplatin. This unsatisfactory situation highlights the necessity of finding factors impacting GC sensibility to therapies. We analyzed the cisplatin pangenomic response in cancer cells and found HDAC4 as a major epigenetic regulator being inhibited. HDAC4 mRNA repression was partly mediated by the cisplatin-induced expression of miR-140. At a functional level, HDAC4 inhibition favored cisplatin cytotoxicity and reduced tumor growth. Inversely, overexpression of HDAC4 inhibits cisplatin cytotoxicity. Importantly, HDAC4 expression was found to be elevated in gastric tumors compared to healthy tissues, and in particular in specific molecular subgroups. Furthermore, mutations in HDAC4 correlate with good prognosis. Pathway analysis of genes whose expression in patients correlated strongly with HDAC4 highlighted DNA damage, p53 stabilization, and apoptosis as processes downregulated by HDAC4. This was further confirmed by silencing of HDAC4, which favored cisplatin-induced apoptosis characterized by cleavage of caspase 3 and induction of proapoptotic genes, such as BIK, in part via a p53-dependent mechanism. Altogether, these results reveal HDAC4 as a resistance factor for cisplatin in GC cells that impacts on patients' survival.
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Affiliation(s)
- Marie-Elodie Spaety
- Laboratory STREINTH (Stress Response and Innovative Therapies), Inserm IRFAC UMR_S1113, Université de Strasbourg, 3 av. Molière, 67200 Strasbourg, France; (M.-E.S.); (A.G.); (A.B.); (A.V.); (B.R.); (C.O.); (A.C.J.); (G.M.)
- Architecture and Reactivity of RNA, Institut de biologie moléculaire et cellulaire du CNRS, Université de Strasbourg, 15 rue René Descartes, 67084 Strasbourg, France;
| | - Alexandre Gries
- Laboratory STREINTH (Stress Response and Innovative Therapies), Inserm IRFAC UMR_S1113, Université de Strasbourg, 3 av. Molière, 67200 Strasbourg, France; (M.-E.S.); (A.G.); (A.B.); (A.V.); (B.R.); (C.O.); (A.C.J.); (G.M.)
| | - Amandine Badie
- Laboratory STREINTH (Stress Response and Innovative Therapies), Inserm IRFAC UMR_S1113, Université de Strasbourg, 3 av. Molière, 67200 Strasbourg, France; (M.-E.S.); (A.G.); (A.B.); (A.V.); (B.R.); (C.O.); (A.C.J.); (G.M.)
| | - Aina Venkatasamy
- Laboratory STREINTH (Stress Response and Innovative Therapies), Inserm IRFAC UMR_S1113, Université de Strasbourg, 3 av. Molière, 67200 Strasbourg, France; (M.-E.S.); (A.G.); (A.B.); (A.V.); (B.R.); (C.O.); (A.C.J.); (G.M.)
- Radiology Department, Centre Hospitalier Universitaire (CHU) Hautepierre, 67200 Strasbourg, France
| | - Benoit Romain
- Laboratory STREINTH (Stress Response and Innovative Therapies), Inserm IRFAC UMR_S1113, Université de Strasbourg, 3 av. Molière, 67200 Strasbourg, France; (M.-E.S.); (A.G.); (A.B.); (A.V.); (B.R.); (C.O.); (A.C.J.); (G.M.)
- Digestive Surgery department, CHU Hautepierre, 67200 Strasbourg, France
| | - Christophe Orvain
- Laboratory STREINTH (Stress Response and Innovative Therapies), Inserm IRFAC UMR_S1113, Université de Strasbourg, 3 av. Molière, 67200 Strasbourg, France; (M.-E.S.); (A.G.); (A.B.); (A.V.); (B.R.); (C.O.); (A.C.J.); (G.M.)
| | | | - Koji Okamoto
- National Cancer Research Center, Tokyo 104_0045, Japan; (K.Y.); (K.O.)
| | - Alain C. Jung
- Laboratory STREINTH (Stress Response and Innovative Therapies), Inserm IRFAC UMR_S1113, Université de Strasbourg, 3 av. Molière, 67200 Strasbourg, France; (M.-E.S.); (A.G.); (A.B.); (A.V.); (B.R.); (C.O.); (A.C.J.); (G.M.)
- Centre de Lutte contre le Cancer Paul Strauss (CLCC), 67065 Strasbourg, France
| | - Georg Mellitzer
- Laboratory STREINTH (Stress Response and Innovative Therapies), Inserm IRFAC UMR_S1113, Université de Strasbourg, 3 av. Molière, 67200 Strasbourg, France; (M.-E.S.); (A.G.); (A.B.); (A.V.); (B.R.); (C.O.); (A.C.J.); (G.M.)
- Centre de Lutte contre le Cancer Paul Strauss (CLCC), 67065 Strasbourg, France
| | - Sébastien Pfeffer
- Architecture and Reactivity of RNA, Institut de biologie moléculaire et cellulaire du CNRS, Université de Strasbourg, 15 rue René Descartes, 67084 Strasbourg, France;
| | - Christian Gaiddon
- Laboratory STREINTH (Stress Response and Innovative Therapies), Inserm IRFAC UMR_S1113, Université de Strasbourg, 3 av. Molière, 67200 Strasbourg, France; (M.-E.S.); (A.G.); (A.B.); (A.V.); (B.R.); (C.O.); (A.C.J.); (G.M.)
- Centre de Lutte contre le Cancer Paul Strauss (CLCC), 67065 Strasbourg, France
- Correspondence:
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30
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Khafaei M, Rezaie E, Mohammadi A, Shahnazi Gerdehsang P, Ghavidel S, Kadkhoda S, Zorrieh Zahra A, Forouzanfar N, Arabameri H, Tavallaie M. miR-9: From function to therapeutic potential in cancer. J Cell Physiol 2019; 234:14651-14665. [PMID: 30693512 DOI: 10.1002/jcp.28210] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Accepted: 01/10/2019] [Indexed: 01/24/2023]
Abstract
Malignant neoplasms are regarded as the main cause of death around the world; hence, many research studies were conducted to further perceive molecular mechanisms, treatment, and cancer prognosis. Cancer is known as a major factor for health-related problems in the world. The main challenges associated with these diseases are prompt diagnosis, disease remission classification and treatment status forecast. Therefore, progressing in such areas by developing new and optimized methods with the help of minimally invasive biological markers such as circular microRNAs (miRNAs) can be considered important. miRNA interactions with target genes have specified their role in development, apoptosis, differentiation, and proliferation and also, confirm direct miRNA function in cancer. Different miRNAs expression levels in various types of malignant neoplasms have been observed to be associated with prognosis of various carcinomas. miR-9 seems to implement opposite practices in different tissues or under various cancer incidences by influencing different genes. Aberrant miR-9 levels have been observed in many cancer types. Therefore, we intended to investigate the precise role of miR-9 in patients with malignant neoplasms. To this end, in this study, we attempted to examine different studies to clarify the overall role of miR-9 as a prognostic marker in several human tumors. The presented data in this study can help us to find the novel therapeutic avenues for treatment of human cancers.
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Affiliation(s)
- Mostafa Khafaei
- Human Genetics Research Center, Baqiyatallah Medical Science University, Tehran, Iran
| | - Ehsan Rezaie
- Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Science, Tehran, Iran
| | - Ali Mohammadi
- Human Genetics Research Center, Baqiyatallah Medical Science University, Tehran, Iran
| | | | - Sara Ghavidel
- Department Cell and Molecular Biology, Tonekabon Branch, Islamic Azad University, Tehran, Iran
| | - Sepideh Kadkhoda
- Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | - Atieh Zorrieh Zahra
- Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | - Narjes Forouzanfar
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Arabameri
- Human Genetics Research Center, Baqiyatallah Medical Science University, Tehran, Iran
| | - Mahmood Tavallaie
- Human Genetics Research Center, Baqiyatallah Medical Science University, Tehran, Iran
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31
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Pei Y, Tang Z, Cai M, Yao Q, Xie B, Zhang X. The E2F3/miR-125a/DKK3 regulatory axis promotes the development and progression of gastric cancer. Cancer Cell Int 2019; 19:212. [PMID: 31423109 PMCID: PMC6693087 DOI: 10.1186/s12935-019-0930-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Accepted: 08/04/2019] [Indexed: 12/20/2022] Open
Abstract
Background Gastric cancer (GC) is one of the most common malignant tumours with high mortality and metastasis rates. E2F3, miR-125a and DKK3 have been reported to be involved in various cancer types, but their detailed roles in GC have not been fully understood. Methods A QRT-PCR assay was used to examine the expression of E2F3, miR-125a and DKK3 in metastatic and nonmetastatic GC tissues. DKK3 plasmids, DKK3 shRNA, miR-125a mimic and miR-125a inhibitor were transfected into BGC823 cells to evaluate the biological functions of DKK3 and miR-125a. A scratch wound healing assay and Transwell assay were utilized to determine the migratory and invasive ability of BGC823 cells transfected with the DKK3 plasmids, DKK3 shRNA, miR-125a mimic and miR-125a inhibitor. Moreover, qRT-PCR and WB analysis were used to analyse the mRNA and protein expression levels of metastasis-related genes after proper transfection. The target relationship between miR-125a and the DKK3 mRNA 3′UTR was determined by a dual luciferase reporter assay, while the interaction between E2F3 and miR-125a was analysed by a ChIP assay. Results The clinical data showed that the DKK3 expression level in metastatic GC samples was significantly less than that in nonmetastatic GC samples, whereas the E2F3 and miR-125a expression levels in metastatic GC samples were notably greater than those in nonmetastatic GC samples. Moreover, knockdown of DKK3 and overexpression of miR-125a markedly promoted the migratory and invasive abilities of GC cells. Additionally, the protein and mRNA expression levels of metastasis-related genes, including N-cadherin, Vimentin, MMP2 and MMP9, were markedly decreased in the DKK3 and miR-125a inhibitor groups compared to their control groups and markedly increased in the DKK3 shRNA and miR-125a groups compared with the control group. Finally, a dual luciferase reporter assay and ChIP assay showed that E2F3 binds to the miR-125a promoter and that the DKK3 mRNA 3′UTR is a direct target of miR-125a. Furthermore, analysis of Kaplan–Meier curves also confirmed the regulatory role of E2F3 on miR-125a. Additionally, BGC823 cells transfected with E2F3 plasmids and shRNA downregulated and upregulated the expression of DKK3, respectively. Conclusion Our results suggested that E2F3 might play a tumour-promoting role in the metastasis and progression of GC by regulating the miR-125a/DKK3 axis.
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Affiliation(s)
- Yihua Pei
- 1Central Laboratory, ZhongShan Hospital XiaMen University, No. 201 Hubin South Road, Xiamen, 361004 Fujian China
| | - Zhiteng Tang
- 2Department of Pathology, ZhongShan Hospital XiaMen University, Xiamen, 361004 Fujian China
| | - Minjing Cai
- 3Department of Center of Clinical Laboratory, ZhongShan Hospital XiaMen University, Xiamen, 361004 Fujian China
| | - Qin Yao
- 1Central Laboratory, ZhongShan Hospital XiaMen University, No. 201 Hubin South Road, Xiamen, 361004 Fujian China
| | - Bozhen Xie
- 4Department of Spine Surgery, ZhongShan Hospital XiaMen University, Xiamen, 361004 Fujian China
| | - Xin Zhang
- 5Department of Rehabilitation, ZhongShan Hospital XiaMen University, Xiamen, 361004 Fujian China
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32
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Li G, Ao S, Hou J, Lyu G. Low expression of miR-125a-5p is associated with poor prognosis in patients with gastric cancer. Oncol Lett 2019; 18:1483-1490. [PMID: 31423214 PMCID: PMC6607383 DOI: 10.3892/ol.2019.10423] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Accepted: 04/16/2019] [Indexed: 12/19/2022] Open
Abstract
microRNAs (miRs) serve critical roles in tumor progression. Low expression of miR-125a in gastric carcinoma (GC) may promote tumor development. In the present study, low expression of miR-125a was confirmed in cancer tissues using The Cancer Genome Atlas database. Additionally, the expression and clinical significance of miR-125a-5p was investigated using reverse transcription-quantitative PCR in 150 cases of GC. The results of the present study demonstrated that the level of miR-125a-5p expression was decreased in GC biopsies compared with that in matched adjacent normal tissues. Low expression of miR-125a-5p was associated with increased tumor diameter, high Ki67 expression and poor overall survival of patients with GC. Multivariate survival analysis demonstrated that low miR-125a-5p expression may be used as an independent prognostic factor for patients with GC. However, no effects on the cell viability in a Cell Counting kit-8 assay, and cell migration and invasion in Transwell assays were detected in response to treatment using miR-125a-5p mimics or inhibitors in vitro. Therefore, the results of the present study provide evidence that low expression of miR-125a-5p may be associated with a poor prognosis, suggesting its value as a tumor biomarker for patients with GC.
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Affiliation(s)
- Guan Li
- Department of Gastrointestinal Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Sheng Ao
- Department of Gastrointestinal Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Jianing Hou
- Department of Gastrointestinal Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Guoqing Lyu
- Department of Gastrointestinal Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
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33
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Tokumaru Y, Tajirika T, Sugito N, Kuranaga Y, Shinohara H, Tsujino T, Matsuhashi N, Futamura M, Akao Y, Yoshida K. Synthetic miR-143 Inhibits Growth of HER2-Positive Gastric Cancer Cells by Suppressing KRAS Networks Including DDX6 RNA Helicase. Int J Mol Sci 2019; 20:ijms20071697. [PMID: 30959742 PMCID: PMC6479539 DOI: 10.3390/ijms20071697] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2019] [Accepted: 04/03/2019] [Indexed: 12/14/2022] Open
Abstract
Gastric cancer (GC) is one of the most common cancers worldwide. In the clinical setting, the identification of HER2 overexpression in GC was a significant finding, as trastuzumab, an anti-HER2 drug, provides a survival advantage to HER2-positive GC patients. In HER2-postive GC, the dysregulation of PI3K/AKT and MAPK/ERK signaling pathways has been reported, and inhibition of these pathways is an important therapeutic strategy. MiR-143 is known to act as a tumor suppressor in several cancers, such as bladder cancer, breast cancer, colorectal cancer, and gastric cancer. In the current study, we developed a novel chemically-modified miR-143 and explored the functions of this synthetic miR-143 (syn-miR-143) in HER2-positive gastric cancer. The expression level of miR-143 was down-regulated in GC cell lines, including HER2-positive GC cell lines, MKN7, and KATO-III. The ectopic expression of miR-143 in those cell lines suppressed cell growth through systemic silencing of KRAS and its effector signaling molecules, AKT and ERK. Furthermore, syn-miR-143 indirectly down-regulated the expression of HER2, an upstream molecule of KRAS, through silencing DEAD/H-box RNA helicase 6 (DDX6), RNA helicase, which enhanced HER2 protein expression at the translational step in HER2-positive GC cells. These findings suggested that syn-miR-143 acted as a tumor suppressor through the impairment of KRAS networks including the DDX6.
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Affiliation(s)
- Yoshihisa Tokumaru
- United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
| | - Toshihiro Tajirika
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
| | - Nobuhiko Sugito
- United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
| | - Yuki Kuranaga
- United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
| | - Haruka Shinohara
- United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
| | - Takuya Tsujino
- United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
- Department of Urology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
| | - Nobuhisa Matsuhashi
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
| | - Manabu Futamura
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
| | - Yukihiro Akao
- United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
| | - Kazuhiro Yoshida
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
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Zou D, Xu L, Li H, Ma Y, Gong Y, Guo T, Jing Z, Xu X, Zhang Y. Role of abnormal microRNA expression in Helicobacter pylori associated gastric cancer. Crit Rev Microbiol 2019; 45:239-251. [PMID: 30776938 DOI: 10.1080/1040841x.2019.1575793] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Epidemiological studies have shown that Helicobacter pylori (HP) infection is a risk factor for gastric cancer (GC). HP infection may induce the release of pro-inflammatory mediators, and abnormally increase the level of reactive oxygen species (ROS), nitric oxide (NO), and cytokines in mucosal epithelial cells of the stomach. However, the specific mechanism underlying the pathogenesis of HP-associated GC is still poorly understood. Recent studies have revealed that abnormal microRNA expression may affect the proliferation, differentiation, and apoptosis of mucosal epithelial cells of the stomach to further influence GC occurrence, development, and metastasis. Herein, we summarize the role of abnormal microRNAs in the regulation of HP-associated GC progression. Abnormal microRNA expression in HP-positive GC may be a biomarker for GC diagnosis, occurrence, and development as well as its targeted treatment and prognosis.
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Affiliation(s)
- Dan Zou
- a The First laboratory of cancer institute , First Hospital of China Medical University , Shenyang , China
| | - Ling Xu
- b Department of Medical Oncology , First Hospital of China Medical University , Shenyang , China
| | - Heming Li
- b Department of Medical Oncology , First Hospital of China Medical University , Shenyang , China.,c Department of Oncology , Affiliated Zhongshan Hospital of Dalian University , Dalian , China
| | - Yanju Ma
- b Department of Medical Oncology , First Hospital of China Medical University , Shenyang , China.,d Department of Medical Oncology , Cancer Hospital of China Medical University , Shenyang , China
| | - Yuehua Gong
- e Department of Tumor Etiology and Screening Department of Cancer Institute and General Surgery, First Hospital of China Medical University , Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department , Shenyang , China
| | - Tianshu Guo
- b Department of Medical Oncology , First Hospital of China Medical University , Shenyang , China
| | - Zhitao Jing
- f Department of Neurosurgery , First Hospital of China Medical University , Shenyang , China
| | - Xiuying Xu
- g Department of Gastroenterology , First Hospital of China Medical University , Shenyang , China
| | - Ye Zhang
- a The First laboratory of cancer institute , First Hospital of China Medical University , Shenyang , China
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Zhou H, Liu H, Jiang M, Zhang S, Chen J, Fan X. Targeting MicroRNA-21 Suppresses Gastric Cancer Cell Proliferation and Migration via PTEN/Akt Signaling Axis. Cell Transplant 2019; 28:306-317. [PMID: 30700111 PMCID: PMC6425105 DOI: 10.1177/0963689719825573] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
MicroRNA plays a pivotal role in various human cancers, especially in human gastric cancer. In the present study, we evaluated the effect of microRNA-21 (miR-21) on the gastric cancer cell proliferation, migration, apoptosis and the related signaling cascades. Here, we showed that down-regulation of miR-21 markedly reduced gastric cancer cell proliferation (AGS and NCI-N87 cells) in a time dependent manner. Moreover, our findings revealed that silencing miR-21 dramatically blocked gastric cancer cell migration and movement, which might be related to down-regulation of vimentin expression. We also found that down-regulation of miR-21 promoted cell apoptosis and repressed cell cycle progression. Further investigation showed that down-regulation of miR-21 significantly increased phosphatase and tensin homolog (PTEN) protein expression level, but not transcription level (mRNA level), which in turn decreased Akt phosphorylation at Thr308 and Ser473. Collectively, our results uncover that miR-21 targets PTEN/Akt signaling pathway and regulates cell proliferation, migration and apoptosis in human gastric cancer cells. Our findings may provide a therapeutic target for treatment of human gastric cancer.
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Affiliation(s)
- Hao Zhou
- 1 Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai, China
| | - Hongyan Liu
- 1 Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai, China
| | - Miao Jiang
- 1 Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai, China
| | - Shaoren Zhang
- 1 Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai, China
| | - Junfeng Chen
- 1 Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai, China
| | - Xiaoming Fan
- 1 Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai, China
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36
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Zhang J, Zhou Y, Huang T, Wu F, Pan Y, Dong Y, Wang Y, Chan AKY, Liu L, Kwan JSH, Cheung AHK, Wong CC, Lo AKF, Cheng ASL, Yu J, Lo KW, Kang W, To KF. FGF18, a prominent player in FGF signaling, promotes gastric tumorigenesis through autocrine manner and is negatively regulated by miR-590-5p. Oncogene 2018; 38:33-46. [PMID: 30082912 PMCID: PMC6318220 DOI: 10.1038/s41388-018-0430-x] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Revised: 06/20/2018] [Accepted: 07/10/2018] [Indexed: 12/14/2022]
Abstract
Fibroblast growth factors (FGFs) and their receptors are significant components during fundamental cellular processes. FGF18 plays a distinctive role in modulating the activity of both tumor cells and tumor microenvironment. This study aims to comprehensively investigate the expression and functional role of FGF18 in gastric cancer (GC) and elucidate its regulatory mechanisms. The upregulation of FGF18 was detected in seven out of eleven (63.6%) GC cell lines. In primary GC samples, FGF18 was overexpressed in genomically stable and chromosomal instability subtypes of GC and its overexpression was associated with poor survival. Knocking down FGF18 inhibited tumor formation abilities, induced G1 phase cell cycle arrest and enhanced anti-cancer drug sensitivity. Expression microarray profiling revealed that silencing of FGF18 activated ATM pathway but quenched TGF-β pathway. The key factors that altered in the related signaling were validated by western blot and immunofluorescence. Meanwhile, treating GC cells with human recombinant FGF18 or FGF18-conditioned medium accelerated tumor growth through activation of ERK-MAPK signaling. FGF18 was further confirmed to be a direct target of tumor suppressor, miR-590-5p. Their expressions showed a negative correlation in primary GC samples and more importantly, re-overexpression of FGF18 partly abolished the tumor-suppressive effect of miR-590-5p. Our study not only identified that FGF18 serves as a novel prognostic marker and a therapeutic target in GC but also enriched the knowledge of FGF-FGFR signaling during gastric tumorigenesis.
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Affiliation(s)
- Jinglin Zhang
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.,Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.,Li Ka Shing Institute of Health Science, Sir Y.K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
| | - Yuhang Zhou
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.,Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.,Li Ka Shing Institute of Health Science, Sir Y.K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
| | - Tingting Huang
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.,Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.,Li Ka Shing Institute of Health Science, Sir Y.K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.,Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, People's Republic of China
| | - Feng Wu
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.,Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.,Li Ka Shing Institute of Health Science, Sir Y.K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
| | - Yi Pan
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.,Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.,Li Ka Shing Institute of Health Science, Sir Y.K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
| | - Yujuan Dong
- Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
| | - Yan Wang
- Key Laboratory of Cardiovascular Medicine and Clinical Pharmacology of Shanxi Province, Shanxi Medical University, Taiyuan, People's Republic of China
| | - Aden K Y Chan
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
| | - Liping Liu
- Department of Hepatobiliary and Pancreatic Surgery, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong Province, People's Republic of China
| | - Johnny S H Kwan
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
| | - Alvin H K Cheung
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
| | - Chi Chun Wong
- Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
| | - Angela K F Lo
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
| | - Alfred S L Cheng
- Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, People's Republic of China.,School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
| | - Jun Yu
- Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.,Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, People's Republic of China.,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
| | - Kwok Wai Lo
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
| | - Wei Kang
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China. .,Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China. .,Li Ka Shing Institute of Health Science, Sir Y.K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China. .,Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, People's Republic of China.
| | - Ka Fai To
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China. .,Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China. .,Li Ka Shing Institute of Health Science, Sir Y.K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China. .,Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, People's Republic of China.
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37
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Vedeld HM, Goel A, Lind GE. Epigenetic biomarkers in gastrointestinal cancers: The current state and clinical perspectives. Semin Cancer Biol 2018; 51:36-49. [PMID: 29253542 PMCID: PMC7286571 DOI: 10.1016/j.semcancer.2017.12.004] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Revised: 11/17/2017] [Accepted: 12/12/2017] [Indexed: 02/07/2023]
Abstract
Each year, almost 4.1 million people are diagnosed with gastrointestinal (GI) cancers. Due to late detection of this disease, the mortality is high, causing approximately 3 million cancer-related deaths annually, worldwide. Although the incidence and survival differs according to organ site, earlier detection and improved prognostication have the potential to reduce overall mortality burden from these cancers. Epigenetic changes, including aberrant promoter DNA methylation, are common events in both cancer initiation and progression. Furthermore, such changes may be identified non-invasively with the use of PCR based methods, in bodily fluids of cancer patients. These features make aberrant DNA methylation a promising substrate for the development of disease biomarkers for early detection, prognosis and for predicting response to therapy. In this article, we will provide an update and current clinical perspectives for DNA methylation alterations in patients with colorectal, gastric, pancreatic, liver and esophageal cancers, and discuss their potential role as cancer biomarkers.
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Affiliation(s)
- Hege Marie Vedeld
- Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway; K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
| | - Ajay Goel
- Center for Gastrointestinal Research, and Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA.
| | - Guro E Lind
- Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway; K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
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38
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Vasuri F, Visani M, Acquaviva G, Brand T, Fiorentino M, Pession A, Tallini G, D’Errico A, de Biase D. Role of microRNAs in the main molecular pathways of hepatocellular carcinoma. World J Gastroenterol 2018; 24:2647-2660. [PMID: 29991871 PMCID: PMC6034147 DOI: 10.3748/wjg.v24.i25.2647] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 05/18/2018] [Accepted: 06/16/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver malignant neoplasia. HCC is characterized by a poor prognosis. The need to find new molecular markers for its diagnosis and prognosis has led to a progressive increase in the number of scientific studies on this topic. MicroRNAs (miRNAs) are small non-coding RNA that play a role in almost all main cellular pathways. miRNAs are involved in the regulation of expression of the major tumor-related genes in carcinogenesis, acting as oncogenes or tumor suppressor genes. The aim of this review was to identify papers published in 2017 investigating the role of miRNAs in HCC tumorigenesis. miRNAs were classified according to their role in the main molecular pathways involved in HCC tumorigenesis: (1) mTOR; (2) Wnt; (3) JAK/STAT; (4) apoptosis; and (5) MAPK. The role of miRNAs in prognosis/response prediction was taken into consideration. Bearing in mind that the analysis of miRNAs in serum and other body fluids would be crucial for clinical management, the role of circulating miRNAs in HCC patients was also investigated. The most represented miRNA-regulated pathway in HCC is mTOR, but apoptosis, Wnt, JAK/STAT or MAPK pathways are also influenced by miRNA expression levels. These miRNAs could thus be used in clinical practice as diagnostic, prognostic or therapeutic targets for HCC treatment.
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Affiliation(s)
- Francesco Vasuri
- Pathology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), S.Orsola-Malpighi Hospital, University of Bologna, Bologna 40138, Italy
| | - Michela Visani
- Department of Medicine (Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale), Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna - School of Medicine, Bologna 40138, Italy
| | - Giorgia Acquaviva
- Department of Medicine (Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale), Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna - School of Medicine, Bologna 40138, Italy
| | - Thomas Brand
- Department of Pharmacy and Biotechnology (Dipartimento di Farmacia e Biotecnologie), University of Bologna, Bologna 40127, Italy
| | - Michelangelo Fiorentino
- Pathology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), S.Orsola-Malpighi Hospital, University of Bologna, Bologna 40138, Italy
| | - Annalisa Pession
- Department of Pharmacy and Biotechnology (Dipartimento di Farmacia e Biotecnologie), Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna, Bologna 40138, Italy
| | - Giovanni Tallini
- Department of Medicine (Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale), Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna - School of Medicine, Bologna 40138, Italy
| | - Antonia D’Errico
- Pathology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), S.Orsola-Malpighi Hospital, University of Bologna, Bologna 40138, Italy
| | - Dario de Biase
- Department of Pharmacy and Biotechnology (Dipartimento di Farmacia e Biotecnologie), Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna, Bologna 40138, Italy
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39
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Abbas M, Faggian A, Sintali DN, Khan GJ, Naeem S, Shi M, Dingding C. Current and future biomarkers in gastric cancer. Biomed Pharmacother 2018; 103:1688-1700. [DOI: 10.1016/j.biopha.2018.04.178] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Revised: 04/24/2018] [Accepted: 04/24/2018] [Indexed: 02/06/2023] Open
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40
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Jiang X, Wang Z. miR-16 targets SALL4 to repress the proliferation and migration of gastric cancer. Oncol Lett 2018; 16:3005-3012. [PMID: 30127890 PMCID: PMC6096186 DOI: 10.3892/ol.2018.8997] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 06/08/2018] [Indexed: 12/14/2022] Open
Abstract
There is increasing evidence that microRNAs (miRNAs) play important roles in tumor progression and development by targeting different genes, including gastric cancer (GC). However, the role of miR-16 in GC is so far unclear. Herein, we examined the function and potential mechanism of miR-16 in GC. Reverse transcription-quantitative PCR found that miR-16 expression was prominently lower in GC tissues while SALL4 expression was frequently higher than normal tissues. Re-expression of miR-16 could suppress GC cell proliferation and migration by MTT and Transwell assay. We confirmed that miR-16 directly targeted SALL4 in regulating GC by luciferase assay. Knockdown of SALL4 inhibited cell proliferation and migration. Furthermore, SALL4 could counteract the inhibition-effect of miR-16 in GC. In conclusion, for the the first time we demonstrated that miR-16 played inhibitory effect through targeting SALL4 in GC cell proliferation and migration. Our study revealed that miR-16/SALL4 axis was critical in regulating the GC development, indicating a new prospect to regulate GC cell progression and development.
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Affiliation(s)
- Xuefeng Jiang
- Department of Gastroenterology, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130000, P.R. China
| | - Zhe Wang
- Department of Gastroenterology, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130000, P.R. China
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41
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Jamali L, Tofigh R, Tutunchi S, Panahi G, Borhani F, Akhavan S, Nourmohammadi P, Ghaderian SM, Rasouli M, Mirzaei H. Circulating microRNAs as diagnostic and therapeutic biomarkers in gastric and esophageal cancers. J Cell Physiol 2018; 233:8538-8550. [DOI: 10.1002/jcp.26850] [Citation(s) in RCA: 105] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2018] [Accepted: 05/10/2018] [Indexed: 12/19/2022]
Affiliation(s)
- Leila Jamali
- Department of Medical Genetics School of Medicine, Shahid Beheshti University of Medical Sciences Tehran Iran
| | | | - Sara Tutunchi
- Department of Medical Genetics Shahid Sadoughi University of Medical Sciences Yazd Iran
| | - Ghodratollah Panahi
- Department of Biochemistry Faculty of Medicine, Tehran University of Medical Sciences Tehran Iran
| | - Fatemeh Borhani
- Department of Basic Sciences Faculty of Medicine, Gonabad University of Medical Sciences Gonabad Iran
- Department of Basic Sciences Faculty of Medicine, Shahid Beheshti University of Medical Sciences Tehran Iran
| | - Saeedeh Akhavan
- Department of Biology School of Basic Sciences, Science and Research Branch, Islamic Azad University Tehran Iran
| | - Parisa Nourmohammadi
- Department of Medical Genetics Shahid Sadoughi University of Medical Sciences Yazd Iran
| | - Sayyed M.H. Ghaderian
- Urogenital Stem Cell Research Shahid Beheshti University of Medical Sciences Tehran Iran
| | - Milad Rasouli
- Department of Immunology Faculty of Medical Sciences, Tarbiat Modares University Tehran Iran
| | - Hamed Mirzaei
- Department of Medical Biotechnology School of Medicine Mashhad University of Medical Sciences Mashhad Iran
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42
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Macedo F, Ladeira K, Longatto-Filho A, Martins SF. Editor’s Pick: Pyruvate Kinase and Gastric Cancer: A Potential Marker. EUROPEAN MEDICAL JOURNAL 2018. [DOI: 10.33590/emj/10313567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
Gastric cancer is the second most common cause of cancer-related deaths worldwide, and the 5-year overall survival rate for advanced gastric cancer is ≤25%. Metabolism is a critical process for maintaining growth and other functions in cancer cells; in these cells, the metabolic process shifts from oxidative phosphorylation to aerobic glycolysis and the expression of pyruvate kinase (PK) splice isoform M2 (PKM2) is upregulated. A PubMed search focussing on PK in gastric cancer was conducted and 32 articles were initially collected; 12 articles were subsequently excluded from this review. PKM2 is responsible for tumour growth and invasion and correlates with short survival times and cancer differentiation. Pyruvate dehydrogenase kinase 1 is associated with cell proliferation, lymph node metastasis, and invasion. Measurement of PKM2 or pyruvate dehydrogenase kinase 1 in the blood or stools could be a good marker for gastric cancer in combination with the glycoprotein CA72-4. The review arose from the need for new biomarkers in the management of gastric cancer and had the primary objective of determining whether PK could be used as a marker to diagnose and monitor gastric cancer.
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Affiliation(s)
- Filipa Macedo
- Portuguese Oncology Institute – Coimbra, Coimbra, Portugal
| | - Kátia Ladeira
- Portuguese Oncology Institute – Lisbon, Lisbon, Portugal; Life and Health Science Research Institute, School of Health Sciences, University of Minho, Braga, Portugal; ICVS/3B’s-PT Government Associate Laboratory, Braga, Portugal
| | - Adhemar Longatto-Filho
- Life and Health Science Research Institute, School of Health Sciences, University of Minho, Braga, Portugal; ICVS/3B’s-PT Government Associate Laboratory, Braga, Portugal 5. Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil; Laboratory of Medical Investigation 14, Faculty of Medicine, University of São Paulo, São Paulo, Brazil
| | - Sandra F. Martins
- Life and Health Science Research Institute, School of Health Sciences, University of Minho, Braga, Portugal; ICVS/3B’s-PT Government Associate Laboratory, Braga, Portugal; Surgery Department, Coloproctology Unit, Braga Hospital, Braga, Portugal
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43
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Lloyd KA, Moore AR, Parsons BN, O'Hara A, Boyce M, Dockray GJ, Varro A, Pritchard DM. Gastrin-induced miR-222 promotes gastric tumor development by suppressing p27kip1. Oncotarget 2018; 7:45462-45478. [PMID: 27323780 PMCID: PMC5216734 DOI: 10.18632/oncotarget.9990] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2016] [Accepted: 05/29/2016] [Indexed: 12/16/2022] Open
Abstract
Background and Aims Elevated circulating concentrations of the hormone gastrin contribute to the development of gastric adenocarcinoma and types-1 and 2 gastric neuroendocrine tumors (NETs). MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate proteins which in turn influence various biological processes. We hypothesised that gastrin induces the expression of specific gastric miRNAs within CCK2 receptor (CCK2R) expressing cells and that these mediate functionally important actions of gastrin. Results Gastrin increased miR-222 expression in AGSGR cells, with maximum changes observed at 10 nM G17 for 24 h. Signalling occurred via CCK2R and the PKC and PI3K pathways. miR-222 expression was increased in the serum and gastric corpus mucosa of hypergastrinemic INS-GAS mice and hypergastrinemic patients with autoimmune atrophic gastritis and type 1 gastric NETs; it decreased in patients following treatment with the CCK2R antagonist netazepide (YF476). Gastrin-induced miR-222 overexpression resulted in reduced expression and cytoplasmic mislocalisation of p27kip1, which in turn caused actin remodelling and increased migration in AGSGR cells. Materials and Methods miRNA PCR arrays were used to identify changes in miRNA expression following G17 treatment of human gastric adenocarcinoma cells stably transfected with CCK2R (AGSGR). miR-222 was further investigated using primer assays and samples from hypergastrinemic mice and humans. Chemically synthesised mimics and inhibitors were used to assess cellular phenotypical changes associated with miR-222 dysregulation. Conclusions These data indicate a novel mechanism contributing to gastrin-associated gastric tumor development. miR-222 may also be a promising biomarker for monitoring gastrin induced premalignant changes in the stomach.
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Affiliation(s)
- Katie A Lloyd
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
| | - Andrew R Moore
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.,Gastroenterology Directorate, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, United Kingdom
| | - Bryony N Parsons
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
| | - Adrian O'Hara
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
| | | | - Graham J Dockray
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
| | - Andrea Varro
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
| | - D Mark Pritchard
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.,Gastroenterology Directorate, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, United Kingdom
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44
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Zabaglia LM, Sallas ML, Santos MPD, Orcini WA, Peruquetti RL, Constantino DH, Chen E, Smith MDAC, Payão SM, Rasmussen LT. Expression of miRNA‐146a, miRNA‐155, IL‐2, and TNF‐α in inflammatory response to
Helicobacter pylori
infection associated with cancer progression. Ann Hum Genet 2017; 82:135-142. [DOI: 10.1111/ahg.12234] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 10/19/2017] [Accepted: 11/10/2017] [Indexed: 02/06/2023]
Affiliation(s)
| | | | | | | | | | | | - Elizabeth Chen
- Universidade Federal de São Paulo (UNIFESP) São Paulo São Paulo Brazil
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45
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Yu L, Chen J, Liu Y, Zhang Z, Duan S. MicroRNA-937 inhibits cell proliferation and metastasis in gastric cancer cells by downregulating FOXL2. Cancer Biomark 2017; 21:105-116. [DOI: 10.3233/cbm-170310] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
This article has been retracted, and the online PDF replaced with this retraction notice.
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46
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MiR-146a functions as a small silent player in gastric cancer. Biomed Pharmacother 2017; 96:238-245. [DOI: 10.1016/j.biopha.2017.09.138] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2017] [Revised: 09/16/2017] [Accepted: 09/26/2017] [Indexed: 12/22/2022] Open
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47
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Xiang Z, Sun M, Yuan Z, Zhang C, Jiang J, Huang S, Xiong B. Prognostic and clinicopathological significance of microRNA-494 overexpression in cancers: a meta-analysis. Oncotarget 2017; 9:1279-1290. [PMID: 29416694 PMCID: PMC5787438 DOI: 10.18632/oncotarget.22633] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Accepted: 10/02/2017] [Indexed: 01/13/2023] Open
Abstract
MicroRNA-494 was revealed as an attractive prognostic biomarker in recent studies. Nevertheless, the prognostic value of microRNA-494 in cancers remains controversial. Current meta-analysis aims to elucidate the precise predictive value of microRNA-494 in various cancers. Eligible studies were identified through multiple search strategies, the hazard ratios (HRs) and their confidence interval (CI) for patient prognostic outcomes were extracted and estimated. The pooled results of fifteen studies indicated that elevated expression of microRNA-494 implies a good overall survival of cancer patients (HR = 0.58, 95% CI: 0.36-0.91); While no significant association was found between the high expression of microRNA-494 and clinicopathological characteristic. Additionally, subgroup analysis revealed that overexpression of microRNA-494 predicted a worse overall survival in non-small cell lung cancer (HR = 2.35, 95% CI: 1.05-5.24) and colorectal cancer (HR = 2.59, 95% CI: 1.62-4.14). As per the subgroup analysis, the cancer type, the anatomy system classification and the ethnic background had influence on the overall survival result. Our findings indicate that elevated expression of microRNA-494 might predict a good overall survival in most cancers, while in non-small cell lung cancer and colorectal cancer, overexpression of microRNA-494 might predict a worse overall survival.
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Affiliation(s)
- Zhenxian Xiang
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan 430071, P. R. China
| | - Min Sun
- Department of General Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, P. R. China
| | - Zewei Yuan
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan 430071, P. R. China
| | - Chunxiao Zhang
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan 430071, P. R. China
| | - Jun Jiang
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan 430071, P. R. China
| | - Sihao Huang
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan 430071, P. R. China
| | - Bin Xiong
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan 430071, P. R. China
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48
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Li H, Liu G, Pan K, Miao X, Xie Y. Methylation-induced downregulation and tumor suppressive role of microRNA-29b in gastric cancer through targeting LASP1. Oncotarget 2017; 8:95880-95895. [PMID: 29221174 PMCID: PMC5707068 DOI: 10.18632/oncotarget.21431] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Accepted: 08/21/2017] [Indexed: 01/09/2023] Open
Abstract
MicroRNAs (miRs) have been demonstrated to play promoting or tumor suppressive roles in various human cancers, but the regulatory mechanism of miR-29b underlying gastric cancer development and progression still remains largely unclear. In the present study, we found that miR-29b was significantly downregulated in gastric cancer tissues and cell lines. Low expression of miR-29b was significantly associated with DNA methylation, and treatment with DNA methyltransferase inhibitor 5-Aza-20-deoxycytidine upregulated miR-29b in gastric cancer cells. In addition, both reduced miR-29b expression and miR-29b methylation were associated with disease progression and poor prognosis in gastric cancer. Restoration of miR-29b caused a reduction in gastric cancer cell proliferation, migration, and invasion, and inhibited tumor growth in vivo. LASP1 was then identified as a target gene of miR-29b in gastric cancer cells. Moreover, upregulation of LASP1 was significantly associated with gastric cancer progression and poor prognosis. Knockdown of LASP1 also suppressed the proliferation, migration, and invasion of gastric cancer cells. Moreover, overexpression of LASP1 impaired the suppressive effects of miR-29b on the malignant phenotypes of gastric cancer cells, suggesting that miR-29b may inhibit gastric cancer growth and metastasis via targeting LASP1. According to these data, miR-29b may be used as a potential therapeutic candidate for gastric cancer.
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Affiliation(s)
- Hui Li
- Department of Anesthesia, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Guoqing Liu
- Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Ke Pan
- Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Xiongying Miao
- Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yong Xie
- Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
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49
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Williams MR, Stedtfeld RD, Tiedje JM, Hashsham SA. MicroRNAs-Based Inter-Domain Communication between the Host and Members of the Gut Microbiome. Front Microbiol 2017; 8:1896. [PMID: 29021788 PMCID: PMC5624305 DOI: 10.3389/fmicb.2017.01896] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2017] [Accepted: 09/15/2017] [Indexed: 12/31/2022] Open
Abstract
The gut microbiome is an important modulator of host gene expression, impacting important functions such as the innate immune response. Recent evidence suggests that the inter-domain communication between the gut microbiome and host may in part occur via microRNAs (small, non-coding RNA molecules) which are often differentially expressed in the presence of bacteria and can even be released and taken up by bacteria. The role of microRNAs in microbiome–host communication in intestinal diseases is not fully understood, particularly in diseases impacted by exposure to environmental toxicants. Here, we review the present knowledge in the areas of microbiome and microRNA expression-based communication, microbiome and intestinal disease relationships, and microRNA expression responses to intestinal diseases. We also examine potential links between host microRNA–microbiota communication and exposure to environmental toxicants by reviewing connections between (i) toxicants and microRNA expression, (ii) toxicants and gut diseases, and (iii) toxicants and the gut microbiome. Future multidisciplinary research in this area is needed to uncover these interactions with the potential to impact how gut-microbiome associated diseases [e.g., inflammatory bowel disease (IBD) and many others] are managed.
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Affiliation(s)
- Maggie R Williams
- Department of Civil and Environmental Engineering, Michigan State University, East Lansing, MI, United States
| | - Robert D Stedtfeld
- Department of Civil and Environmental Engineering, Michigan State University, East Lansing, MI, United States
| | - James M Tiedje
- Center for Microbial Ecology, Michigan State University, East Lansing, MI, United States.,Department of Plant, Soil, and Microbial Sciences, Michigan State University, East Lansing, MI, United States
| | - Syed A Hashsham
- Department of Civil and Environmental Engineering, Michigan State University, East Lansing, MI, United States.,Center for Microbial Ecology, Michigan State University, East Lansing, MI, United States
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50
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Zhou Y, Li R, Yu H, Wang R, Shen Z. microRNA-130a is an oncomir suppressing the expression of CRMP4 in gastric cancer. Onco Targets Ther 2017; 10:3893-3905. [PMID: 28831264 PMCID: PMC5548272 DOI: 10.2147/ott.s139443] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Gastric cancer is one of the most common causes of death worldwide, although its incidence has steadily declined in recent years. There is strong evidence that aberrantly expressed microRNAs (miRNAs) are involved in gastric cancer tumorigenesis. Furthermore, CRMP4 is closely associated with the occurrence and development of gastric cancer, and our predictions suggest that miR-130a, which can promote gastric cancer tumorigenesis, is a potential CRMP4 regulator. In this study, we investigated the expression of CRMP4 and miR-130a in human gastric cancer cell lines by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot (WB) examination and direct interactions between miR-130a and CRMP4 by dual-luciferase reporter assay. We also evaluated the biological roles of miR-130a and CRMP4 in gastric cancer cells by flow cytometry, MTT assay, soft agar colony formation assay, and Transwell tests and confirmed CRMP4 function in vivo, using a tumor xenograft model. Our results demonstrated that CRMP4 expression was significantly decreased at both the gene and protein levels, while miR-130a expression was notably increased, in five human gastric cancer cell lines compared with human gastric epithelial cells. Dual-luciferase reporter assays indicated that CRMP4 was the direct target of miR-130a. Moreover, an inverse regulatory relationship between miR-130a and CRMP4 was verified by qRT-PCR and WB, and overexpression of miR-130a in BGC823 cells enhanced apoptosis and cell proliferation, arrested the cell cycle in G0/G1, and facilitated cell colony formation, invasion, migration, and adhesion, while upregulation of CRMP4 had opposite effects. Finally, the growth and weight of transplanted tumors derived from BGC823 cells in which CRMP4 was knocked down were remarkably reduced. These data indicate that miR-130a is an oncomir targeting CRMP4 and could be developed as a potential prognostic factor and a novel therapeutic target in gastric cancer.
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Affiliation(s)
- Yiran Zhou
- Department of Pharmacy, Kunming Medical University
- Yan’an Hospital Affiliated to Kunming Medical University, Kunming, People’s Republic of China
| | - Ruhong Li
- Yan’an Hospital Affiliated to Kunming Medical University, Kunming, People’s Republic of China
| | - Haidong Yu
- Yan’an Hospital Affiliated to Kunming Medical University, Kunming, People’s Republic of China
| | - Ruotian Wang
- Yan’an Hospital Affiliated to Kunming Medical University, Kunming, People’s Republic of China
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