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1
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Ma J, Zhao X, Shi L. Circ 003390/Eukaryotic translation initiation factor 4A3 promoted cell migration and proliferation in endometrial cancer via vascular endothelial growth factor signaling by miR-195-5p. Bioengineered 2022; 13:11958-11972. [PMID: 35546509 PMCID: PMC9276038 DOI: 10.1080/21655979.2022.2069358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
The differential expression of circRNA in different biological samples renders it as an ideal biomarker for disease diagnosis and identification of tissue development. In addition, the gradual clarification of the mode of action of circRNA in disease makes it as a potential therapeutic target. The purpose of this study is to investigate the role and regulating mechanism of circular RNA has circ 003390 (circWEE1) on Endometrial cancer (EC) genesis. To estimate clinical values of circWEE1 on cell migration and proliferation in EC, and its possible mechanisms. The expression of circWEE1 and EIF4A3in EC cells have been evaluated using qPCR and Western blot. The expression of circWEE1 and EIF4A3 levels were increased in patients with EC. Over-expression of circWEE1 or down-regulation of miR-195-5p promoted cell migration and proliferation in EC. Next, we verified that eIF4A3 binds to the circWEE1 mRNA transcript, circWEE1 served as a sponge that directly targeted miR-195-5p. Bioinformatics prediction forecast that miR-195-5p directly targeted VEGF at 3'-UTR, which was confirmed by luciferase reporter assay. Our findings indicate that Circular RNA hsa circWEE1/EIF4A3 promoted cell migration and proliferation in EC via VEGF signaling by miR-195-5p, which could provide pivotal potential therapeutic targets for the treatment of EC.
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Affiliation(s)
- Jing Ma
- Department of Gynecology and Obstetrics, The Forth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xiwa Zhao
- Department of Gynecology and Obstetrics, The Forth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Li Shi
- Department of Gynecology and Obstetrics, The Forth Hospital of Hebei Medical University, Shijiazhuang, China
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2
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Lee IH, Kim G, Kwak SG, Baek DW, Kang BW, Kim HJ, Park SY, Park JS, Choi GS, Hur K, Kim JG. Predictive Value of Circulating miRNAs in Lymph Node Metastasis for Colon Cancer. Genes (Basel) 2021; 12:genes12020176. [PMID: 33513887 PMCID: PMC7912296 DOI: 10.3390/genes12020176] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 01/18/2021] [Accepted: 01/25/2021] [Indexed: 12/13/2022] Open
Abstract
(1) Background: Lymph node (LN) status is an indubitable prognostic factor for survival among colon cancer patients. MicroRNAs (miRNAs) have been implicated in the development and progression of many cancers and are potential biomarkers for cancer diagnosis and prognosis. Therefore, we validated candidate biomarkers using circulating miRNAs by analyzing the plasma miRNA concentrations from patients with colon cancer to predict LN metastasis. (2) Methods: This study included 79 blood samples from patients diagnosed with colon cancer. The NanoString assay was used for screening, and TaqMan miRNA assays for quantitative real-time polymerase chain reaction (RT-PCR) test was used for validation. In a discovery set, we compared the expression of 800 circulating miRNAs in 24 samples (stage 0/I/IIA versus IIIB/IIIC). For validation, a total 79 samples were tested using quantitative RT-PCR. (3) Results: In the discovery set, 10 candidate circulating miRNAs were detected (4 up-regulated miRNAs: miR-323a-3p, miR-382-5p, miR-29a-3p, and miR-376a-3p; 6 down-regulated miRNAs: miR-26a-5p, let-7g-5p, miR-15b-5p, miR-142-3p, miR-374a-5p, and let-7b-5p). In the validation set, higher expression of three circulating miRNAs (miR-323a-3p, miR-382-5p, and miR-376a-3p) was significantly associated with LN metastasis (p = 0.0063, 0.0107, and 0.0022). (4) Conclusions: High expression of circulating miR-323a-3p, miR-382-5p, and miR-376a-3p was significantly associated with LN metastasis in colon cancer patients. These miRNAs could be circulating biomarker candidates that predict the presence of LN metastasis.
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Affiliation(s)
- In Hee Lee
- Division of Hematology/Oncology, Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu 42112, Korea;
| | - Gyeonghwa Kim
- Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 41404, Korea;
| | - Sang Gyu Kwak
- Department of Medical Statistics, Daegu Catholic University School of Medicine, Daegu 42112, Korea;
| | - Dong Won Baek
- Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University Cancer Research Institute, Kyungpook National University, Daegu 41404, Korea; (D.W.B.); (B.W.K.)
| | - Byung Woog Kang
- Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University Cancer Research Institute, Kyungpook National University, Daegu 41404, Korea; (D.W.B.); (B.W.K.)
| | - Hye Jin Kim
- Department of Surgery, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University Cancer Research Institute, Kyungpook National University, Daegu 41404, Korea; (H.J.K.); (S.y.P.); (J.S.P.); (G.-S.C.)
| | - Su yeon Park
- Department of Surgery, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University Cancer Research Institute, Kyungpook National University, Daegu 41404, Korea; (H.J.K.); (S.y.P.); (J.S.P.); (G.-S.C.)
| | - Jun Seok Park
- Department of Surgery, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University Cancer Research Institute, Kyungpook National University, Daegu 41404, Korea; (H.J.K.); (S.y.P.); (J.S.P.); (G.-S.C.)
| | - Gyu-Seog Choi
- Department of Surgery, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University Cancer Research Institute, Kyungpook National University, Daegu 41404, Korea; (H.J.K.); (S.y.P.); (J.S.P.); (G.-S.C.)
| | - Keun Hur
- Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 41404, Korea;
- Correspondence: (K.H.); (J.G.K.)
| | - Jong Gwang Kim
- Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University Cancer Research Institute, Kyungpook National University, Daegu 41404, Korea; (D.W.B.); (B.W.K.)
- Correspondence: (K.H.); (J.G.K.)
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3
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Wu H, Yan H. Expression and diagnostic value of miR-34c and miR-141 in serum of patients with colon cancer. Oncol Lett 2020; 20:98. [PMID: 32831917 PMCID: PMC7439149 DOI: 10.3892/ol.2020.11959] [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: 10/16/2019] [Accepted: 07/21/2020] [Indexed: 12/12/2022] Open
Abstract
Expression of miR-34c and miR-141 in serum of colon cancer patients and their association with clinicopathological features and diagnostic value for colon cancer were investigated. A total of 64 patients with colon cancer admitted to Hubei Cancer Hospital from January 2016 to March 2018 were included in the experimental group, and 64 healthy subjects undergoing physical examination during the same period were the control group. The expression of miR-34c and miR-141 in serum of patients in the two groups were detected by RT-qPCR, and the association of miR-34c and miR-141 with the clinicopathological characteristics of colon cancer patients was analyzed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic efficiency of miR-34c and miR-141 in colon cancer. The expression of miR-141 in serum of patients in the experimental group was significantly higher than that in the control group (P<0.05). Expression of miR-34c in serum of patients in the experimental group was significantly lower than that in the control group (P<0.05) and the expression of miR-34c and miR-141 in serum of the experimental group were associated with tumor diameter, clinical stage, degree of differentiation and lymph node metastasis (P<0.05). AUC of serum miR-34c in the diagnosis of colon cancer was 0.857 (95% CI: 0.795-0.919), with the cut-off value of 0.800, the diagnostic sensitivity of 84.38%, and the specificity of 68.75% and AUC of serum miR-141 in the diagnosis of colon cancer was 0.876 (95% CI: 0.810-0.941), with the cut-off value of 0.282, the diagnostic sensitivity of 70.31%, and the specificity of 96.88%. The ROC curve for the diagnosis of colon cancer was further plotted in combination with serum miR-34c and miR-141. AUC of the two combined for the diagnosis of colon cancer was 0.929 (95% CI: 0.884-0.974), with the cut-off value of 0.566, the diagnostic sensitivity of 84.38%, and the specificity of 93.75%. In conclusion, miR-34c and miR-141 might be involved in the occurrence and progression of colon cancer and could be used as biological indicators for early diagnosis of colon cancer.
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Affiliation(s)
- Huijing Wu
- Department of Medical Oncology, Radio-Chemotherapy Center, Hubei Cancer Hospital, Wuhan, Hubei 430079, P.R. China
| | - Hongxia Yan
- Department of Oncological Radiotherapy, Hubei Cancer Hospital, Wuhan, Hubei 430079, P.R. China
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4
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Chen H, Kong Y, Yao Q, Zhang X, Fu Y, Li J, Liu C, Wang Z. Three hypomethylated genes were associated with poor overall survival in pancreatic cancer patients. Aging (Albany NY) 2020; 11:885-897. [PMID: 30710069 PMCID: PMC6382432 DOI: 10.18632/aging.101785] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2018] [Accepted: 01/15/2019] [Indexed: 01/29/2023]
Abstract
Pancreatic cancer (PC) is a highly malignant cancer with poor prognosis and high mortality. Aberrant DNA methylation plays a critical role in the occurrence, progression and prognosis of malignant tumors. In this study, we employed multiple datasets from APGI, TCGA and GEO to perform Multi-Omics analysis, including DNA methylation and expression profiling analysis. Three differentially expressed genes (SULT1E1, IGF2BP3, MAP4K4) with altered status of DNA methylation were identified and then enrolled into prognostic risk score model using LASSO regression. Univariate cox regression analysis indicated that high risk score was significantly associated with poor prognosis. Multivariate cox regression analysis proved the risk score was an independent prognostic factor for PC. In addition, time-dependent ROC curves indicated good performance of our model in predicting the 1-, 3- and 5-year survival of PC patients. Besides, stratified survival analysis revealed that the risk score model had greater prognostic value for patients of late stage with T3/T4 and N+. Pathway enrichment analysis suggested that these three genes might promote tumor progression by affecting signaling by Rho GTPases and chromosome segregation. In summary, three hypomethylated gene signature were significantly associated with patients' overall survival, which might serve as potential prognostic biomarkers for PC patients.
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Affiliation(s)
- Huiming Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.,Department of General Surgery, Shaanxi Provincial Rehabilitation Hospital,Xi'an 710065, Shaanxi, China
| | - Yan Kong
- Department of Clinical Laboratory, Liaocheng People's Hospital, Taishan Medical College, Liaocheng 252000, Shandong, China
| | - Qing Yao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Xing Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Yunong Fu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Jia Li
- Department of Orthopaedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Chang Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Zheng Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
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5
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Qian T, Shi S, Xie L, Zhu Y. miR-938 promotes cell proliferation by regulating RBM5 in lung adenocarcinoma cells. Cell Biol Int 2020; 44:295-305. [PMID: 31498514 DOI: 10.1002/cbin.11233] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Accepted: 08/31/2019] [Indexed: 01/24/2023]
Abstract
A growing body of research suggests that microRNAs (miRNAs) may play a key part in the progression of various cancers, including lung adenocarcinoma (LUAD). However, the expression and mechanism of miR-938 (microRNA-938) in LUAD have not been defined. Compared with adjacent tissues, the level of miR-938 was up-regulated in LUAD tissues. miR-938 expression was significantly associated with tumor size. In vitro assays indicated that miR-938 expression was also increased in the LUAD cell lines. Overexpression of miR-938 promoted LUAD cell proliferation, whereas down-regulation of miR-938 had the opposite effect. We identified RNA-binding protein 5 (RBM5) as a potential target gene of miR-938 in LUAD. Expression of RBM5 was down-regulated in LUAD tumor tissues and negatively correlated with expression of miR-938. Up-regulation of RBM5 reversed cell proliferation by inhibition of miR-938 expression in LUAD cells. These results showed that miR-938 may act as an oncogenic miRNA by targeting RBM5 in LUAD, indicating that miR-938 could be used as a potential therapeutic target for LUAD patients.
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Affiliation(s)
- Taotao Qian
- Department of Thoracic Surgery, Suzhou Ninth People's Hospital, 2666 Ludang Road, Taihu New City, Wujiang District, Suzhou, Jiangsu Province, 215000, China.,Department of Thoracic Surgery, Wujiang People's Hospital Affiliated to Nantong University, 2666 Ludang Road, Taihu New City, Wujiang District, Suzhou, Jiangsu Province, 215000, China
| | - Shunbin Shi
- Department of Thoracic Surgery, Suzhou Ninth People's Hospital, 2666 Ludang Road, Taihu New City, Wujiang District, Suzhou, Jiangsu Province, 215000, China.,Department of Thoracic Surgery, Wujiang People's Hospital Affiliated to Nantong University, 2666 Ludang Road, Taihu New City, Wujiang District, Suzhou, Jiangsu Province, 215000, China
| | - Lincen Xie
- Department of Thoracic Surgery, Suzhou Ninth People's Hospital, 2666 Ludang Road, Taihu New City, Wujiang District, Suzhou, Jiangsu Province, 215000, China.,Department of Thoracic Surgery, Wujiang People's Hospital Affiliated to Nantong University, 2666 Ludang Road, Taihu New City, Wujiang District, Suzhou, Jiangsu Province, 215000, China
| | - Yong Zhu
- Department of Thoracic Surgery, Suzhou Ninth People's Hospital, 2666 Ludang Road, Taihu New City, Wujiang District, Suzhou, Jiangsu Province, 215000, China.,Department of Thoracic Surgery, Wujiang People's Hospital Affiliated to Nantong University, 2666 Ludang Road, Taihu New City, Wujiang District, Suzhou, Jiangsu Province, 215000, China
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6
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Epithelial-Mesenchymal Transition-Related MicroRNAs and Their Target Genes in Colorectal Cancerogenesis. J Clin Med 2019; 8:jcm8101603. [PMID: 31623346 PMCID: PMC6832722 DOI: 10.3390/jcm8101603] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 09/26/2019] [Accepted: 09/27/2019] [Indexed: 02/06/2023] Open
Abstract
MicroRNAs of the miR-200 family have been shown experimentally to regulate epithelial-mesenchymal transition (EMT). Although EMT is the postulated mechanism of development and progression of colorectal cancer (CRC), there are still limited and controversial data on expression of miR-200 family and their target genes during CRC cancerogenesis. Our study included formalin-fixed paraffin-embedded biopsy samples of 40 patients (10 adenomas and 30 cases of CRC with corresponding normal mucosa). Expression of miR-141, miR-200a/b/c and miR-429 and their target genes (CDKN1B, ONECUT2, PTPN13, RND3, SOX2, TGFB2 and ZEB2) was analysed using quantitative real-time PCR. Expression of E-cadherin was analysed using immunohistochemistry. All miRNAs were down-regulated and their target genes showed the opposite expression in CRC compared to adenoma. Down-regulation of the miR-200 family at the invasive front in comparison to the central part of tumour was observed as well as a correlation of expression of miR-200b, CDKN1B, ONECUT2 and ZEB2 expression to nodal metastases. Expression of the miR-200 family and SOX2 also correlated with E-cadherin staining. These results suggest that the miR-200 family and their target genes contribute to progression of adenoma to CRC, invasive properties and development of metastases. Our results strongly support the postulated hypotheses of partial EMT and intra-tumour heterogeneity during CRC cancerogenesis.
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7
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Xu SJ, Hu HT, Li HL, Chang S. The Role of miRNAs in Immune Cell Development, Immune Cell Activation, and Tumor Immunity: With a Focus on Macrophages and Natural Killer Cells. Cells 2019; 8:cells8101140. [PMID: 31554344 PMCID: PMC6829453 DOI: 10.3390/cells8101140] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 09/17/2019] [Accepted: 09/18/2019] [Indexed: 12/13/2022] Open
Abstract
The tumor microenvironment (TME) is the primary arena where tumor cells and the host immune system interact. Bidirectional communication between tumor cells and the associated stromal cell types within the TME influences disease initiation and progression, as well as tumor immunity. Macrophages and natural killer (NK) cells are crucial components of the stromal compartment and display either pro- or anti-tumor properties, depending on the expression of key regulators. MicroRNAs (miRNAs) are emerging as such regulators. They affect several immune cell functions closely related to tumor evasion of the immune system. This review discusses the role of miRNAs in the differentiation, maturation, and activation of immune cells as well as tumor immunity, focusing particularly on macrophages and NK cells.
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Affiliation(s)
- Shi Jun Xu
- Department of Radiology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, China.
| | - Hong Tao Hu
- Department of Minimal Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, China.
| | - Hai Liang Li
- Department of Radiology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, China.
- Department of Minimal Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, China.
| | - Suhwan Chang
- Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 05505, Korea.
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8
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Wu W, He L, Huang Y, Hou L, Zhang W, Zhang L, Wu C. MicroRNA-510 Plays Oncogenic Roles in Non-Small Cell Lung Cancer by Directly Targeting SRC Kinase Signaling Inhibitor 1. Oncol Res 2019; 27:879-887. [PMID: 30982489 PMCID: PMC7848405 DOI: 10.3727/096504018x15451308507747] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
An increasing number of studies have demonstrated that microRNAs (miRNAs) may play key roles in various cancer carcinogenesis and progression, including non-small cell lung cancer (NSCLC). However, the expressions, roles, and mechanisms of miR-510 in NSCLC have, up to now, been largely undefined. In vivo assay showed that miR-510 was upregulated in NSCLC tissues compared with that in adjacent nontumor lung tissues. miR-510 expression was significantly correlated with TNM stage and lymph node metastasis. In vitro assay indicated that expressions of miR-510 were also increased in NSCLC cell lines. Downregulation of miR-510 suppressed NSCLC cell proliferation and invasion in vitro. We identified SRC kinase signaling inhibitor 1 (SRCIN1) as a direct target gene of miR-510 in NSCLC. Expression of SRCIN1 was downregulated in lung cancer cells and negatively correlated with miR-510 expression in tumor tissues. Downregulation of SRCIN1, leading to inhibition of miR-510 expression, reversed cell proliferation and invasion in NSCLC cells. These results showed that miR-510 acted as an oncogenic miRNA in NSCLC, partly by targeting SRCIN1, suggesting that miR-510 can be a potential approach for the treatment of patients with malignant lung cancer.
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Affiliation(s)
- Wei Wu
- Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Linyan He
- Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, P.R. China
| | - Yan Huang
- Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Likun Hou
- Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Wei Zhang
- Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Liping Zhang
- Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R. China
| | - Chunyan Wu
- Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R. China
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9
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Lemberger M, Loewenstein S, Lubezky N, Nizri E, Pasmanik-Chor M, Barazovsky E, Klausner JM, Lahat G. MicroRNA profiling of pancreatic ductal adenocarcinoma (PDAC) reveals signature expression related to lymph node metastasis. Oncotarget 2019; 10:2644-2656. [PMID: 31080555 PMCID: PMC6498999 DOI: 10.18632/oncotarget.26804] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Accepted: 02/22/2019] [Indexed: 12/13/2022] Open
Abstract
Lymph node (LN) metastasis occurs frequently in pancreatic ductal adenocarcinoma (PDAC), representing an advanced disease stage and independently predicting patient survival. Current nodal staging is inadequate preoperatively and even less so postoperatively, and molecular biomarkers are needed to improve prognostication and selection of therapy. Recent data have suggested important roles of miRNAs in PDAC tumorigenesis and progression. The aim of the present study was to identify miRNA expression signature for nodal spread in PDAC patients. Using PDAC human tissue specimens, we identified 39 miRNAs which were differently expressed in LN positive compared to LN negative PDAC samples. Of them, six miRNAs have been reported to play a role in cancer invasion and metastasis. A high versus low six- miRNA signature score was predictive of LN metastasis in the PDAC validation cohort. We demonstrated a similar expression pattern of four out of the six miRNAs in the plasma of PDAC patients. The results of our in-vitro studies revealed that miR-141 and miR-720 are involved in the process of epithelial to mesenchymal-transition in PDAC. These miRNAs significantly inhibited in vitro proliferation, migration and invasion of PDAC cells as evidence by gain- and loss- of function studies, specifically, via ZEB-1 and TWIST1 transcription factors, as well as through the activation of the MAP4K4/JNK signaling pathway.
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Affiliation(s)
- Moran Lemberger
- Laboratory of Surgical Oncology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.,Division of Surgery, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
| | - Shelly Loewenstein
- Laboratory of Surgical Oncology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.,Division of Surgery, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
| | - Nir Lubezky
- Laboratory of Surgical Oncology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.,Division of Surgery, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.,Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Eran Nizri
- Laboratory of Surgical Oncology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.,Division of Surgery, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.,Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | | | - Eli Barazovsky
- Institute of Pathology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
| | - Joseph M Klausner
- Division of Surgery, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.,Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.,The Nikolas and Elizabeth Shlezak Cathedra for Experimental Surgery, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Guy Lahat
- Laboratory of Surgical Oncology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.,Division of Surgery, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.,Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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10
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Chen M, Xu R, Rai A, Suwakulsiri W, Izumikawa K, Ishikawa H, Greening DW, Takahashi N, Simpson RJ. Distinct shed microvesicle and exosome microRNA signatures reveal diagnostic markers for colorectal cancer. PLoS One 2019; 14:e0210003. [PMID: 30608951 PMCID: PMC6319712 DOI: 10.1371/journal.pone.0210003] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Accepted: 12/14/2018] [Indexed: 12/31/2022] Open
Abstract
Extracellular vesicle (EV) microRNAs are of major interest as potential diagnostic biomarkers in all cancer types. This study aims to identify miRNA profiles of shed microvesicles (sMVs) and exosomes (Exos) secreted from the isogenic colorectal cancer (CRC) cell lines SW480 and SW620 and evaluate their ability to predict CRC. Deep sequencing of miRNAs in parental cell lysates (CLs) and highly-purified sMVs and Exos was performed. We focused on miRNAs enriched in EVs and dysregulated miRNAs in metastatic cells (SW620) relative to primary cancer cells (SW480). We investigated the ability of EV miRNA signatures to predict CRC tumours using 594 tumours (representing different pathological stages) and 11 normal samples obtained from TCGA. In SW480 and SW620 cells we identified 345 miRNAs, of which 61 and 73 were upregulated and downregulated in SW620-CLs compared to SW480-CLs, respectively. Selective distribution of cellular miRNAs into EVs results in distinct miRNA signatures for sMVs and Exos in each cell line. Cross cell line comparisons of EV miRNA profiles reveal a subset of miRNAs critical in CRC progression from primary carcinoma to metastasis. Many miRNAs non-detectable (<5 TPM) in CLs were significantly enriched (>1000 TPM) in secreted EVs. Strikingly, miR-7641 which is non-detectable in SW480-CL but upregulated in SW620-CL is highly enriched in EVs secreted from both cell lines. Pearson correlation analysis demonstrated that EV miRNA profiles can be used to predict CRC tumours with ~96% accuracy. Our findings suggest that EV miRNA profiles from CRC cell lines may allow prediction of CRC tumours, and that miR-7641 may serve as an attractive candidate for the specific, non-invasive diagnosis and prognosis of CRC.
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Affiliation(s)
- Maoshan Chen
- Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Melbourne, Australia
- * E-mail: (MC); (RJS)
| | - Rong Xu
- Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Melbourne, Australia
| | - Alin Rai
- Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Melbourne, Australia
| | - Wittaya Suwakulsiri
- Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Melbourne, Australia
| | - Keiichi Izumikawa
- Department of Applied Biological Science, Graduate School of Agriculture, and Global Innovation Research Organisation, Tokyo University of Agriculture and Technology, Tokyo Japan
| | - Hideaki Ishikawa
- Department of Applied Biological Science, Graduate School of Agriculture, and Global Innovation Research Organisation, Tokyo University of Agriculture and Technology, Tokyo Japan
| | - David W. Greening
- Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Melbourne, Australia
| | - Nobuhiro Takahashi
- Department of Applied Biological Science, Graduate School of Agriculture, and Global Innovation Research Organisation, Tokyo University of Agriculture and Technology, Tokyo Japan
| | - Richard J. Simpson
- Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Melbourne, Australia
- * E-mail: (MC); (RJS)
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11
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Chemotherapy-induced miR-141/MAP4K4 signaling suppresses progression of colorectal cancer. Biosci Rep 2018; 38:BSR20180978. [PMID: 30429233 PMCID: PMC6435556 DOI: 10.1042/bsr20180978] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Revised: 11/02/2018] [Accepted: 11/04/2018] [Indexed: 02/07/2023] Open
Abstract
One of the treatment failures for colorectal cancer (CRC) is resistance to chemotherapy drugs. miRNAs have been demonstrated to be a new regulator of pathobiological processes in various tumors. While few studies have explored the specific role of miR-141 in mediating 5-fluorouracil (5-FU) sensitivity of CRC cells, the present study aimed to detect the contribution of miR-141 in 5-FU sensitivity. The CRC cells viability was measured by MTS assay and cell colony forming. The expression of miR-141 and its downstream targets were assessed by reverse transcription quantitative PCR, Western blotting, and immunohistochemistry. The functional assays were conducted using CRC cells and nude mice. At the present study, we found overexpression of miR-141 could inhibit proliferation, migration, tumor-forming and invasive potential of CRC cells in vitro and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) was verified as a directed target of miR-141 The combination treatment of miR-141 with 5-FU, directly targetting MAP4K4, could better inhibit invasion and metastasis of CRC cells colony than either one alone. Furthermore, overexpression of miR-141, targetting MAP4K4, enhanced the effected of 5-FU and suppressed the malignant biological behaviors, in vivo Our findings showed that 5-FU inhibited malignant behavior of human CRC cells in vitro and in vivo by enhancing the efficiency of miR-141 Our data suggested that targetting the miR-141/MAP4K4 signaling pathway could be a potential molecular target that may enhance chemotherapeutic efficacy in the treatment of CRC.
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12
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Liang Y, Zhang C, Ma MH, Dai DQ. Identification and prediction of novel non-coding and coding RNA-associated competing endogenous RNA networks in colorectal cancer. World J Gastroenterol 2018; 24:5259-5270. [PMID: 30581274 PMCID: PMC6295837 DOI: 10.3748/wjg.v24.i46.5259] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2018] [Revised: 10/18/2018] [Accepted: 11/09/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To identify and predict the competing endogenous RNA (ceRNA) networks in colorectal cancer (CRC) by bioinformatics analysis.
METHODS In the present study, we obtained CRC tissue and normal tissue gene expression profiles from The Cancer Genome Atlas project. Differentially expressed (DE) genes (DEGs) were identified. Then, upregulated and downregulated miRNA-centered ceRNA networks were constructed by analyzing the DEGs using multiple bioinformatics approaches. DEmRNAs in the ceRNA networks were identified in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using KEGG Orthology Based Annotation System 3.0. The interactions between proteins were analyzed using the STRING database. Kaplan-Meier survival analysis was conducted for DEGs and real time quantitative polymerase chain reaction (RT-qPCR) was also performed to validate the prognosis-associated lncRNAs in CRC cell lines.
RESULTS Eighty-one DElncRNAs, 20 DEmiRNAs, and 54 DEmRNAs were identified to construct the ceRNA networks of CRC. The KEGG pathway analysis indicated that nine out of top ten pathways were related with cancer and the most significant pathway was “colorectal cancer”. Kaplan-Meier survival analysis showed that the overall survival was positively associated with five DEGs (IGF2-AS, POU6F2-AS2, hsa-miR-32, hsa-miR-141, and SERPINE1) and it was negatively related to three DEGs (LINC00488, hsa-miR-375, and PHLPP2). Based on the STRING protein database, it was found that SERPINE1 and PHLPP2 interact with AKT1. Besides, SERPINE1 can interact with VEGFA, VTN, TGFB1, PLAU, PLAUR, PLG, and PLAT. PHLPP2 can interact with AKT2 and AKT3. RT-qPCR revealed that the expression of IGF2-AS, POU6F2-AS2, and LINC00488 in CRC cell lines was consistent with the in silico results.
CONCLUSION CeRNA networks play an important role in CRC. Multiple DEGs are related with clinical prognosis, suggesting that they may be potential targets in tumor diagnosis and treatment.
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Affiliation(s)
- Yu Liang
- Department of Gastrointestinal Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, Liaoning Province, China
| | - Cheng Zhang
- Department of Gastrointestinal Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, Liaoning Province, China
| | - Ming-Hui Ma
- Department of Gastrointestinal Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, Liaoning Province, China
| | - Dong-Qiu Dai
- Department of Gastrointestinal Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, Liaoning Province, China
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13
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Samir N, Matboli M, El-Tayeb H, El-Tawdi A, Hassan MK, Waly A, El-Akkad HAE, Ramadan MG, Al-Belkini TN, El-Khamisy S, El-Asmar F. Competing endogenous RNA network crosstalk reveals novel molecular markers in colorectal cancer. J Cell Biochem 2018; 119:6869-6881. [PMID: 29737552 DOI: 10.1002/jcb.26884] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Accepted: 03/21/2018] [Indexed: 01/09/2023]
Abstract
The competing endogenous RNA networks play a pivotal role in cancer diagnosis and progression. Novel properstrategies for early detection of colorectal cancer (CRC) are strongly needed. We investigated a novel CRC-specific RNA-based integrated competing endogenous network composed of lethal3 malignant brain tumor like1 (L3MBTL1) gene, long non-coding intergenic RNA- (lncRNA RP11-909B2.1) and homo sapiens microRNA-595 (hsa-miRNA-595) using in silico data analysis. RT-qPCR-based validation of the network was achieved in serum of 70 patients with CRC, 40 patients with benign colorectal neoplasm, and 20 healthy controls. Moreover, in cancer tissues of 20 of the 70 CRC cases were involved in the study. The expression of RNA-based biomarker network in both CRC and adjacent non-tumor tissues and their correlation with the serum levels of this network members was investigated. Lastly, the expression levels of the chosen ceRNA was verified in CRC cell line. Our results revealed that the three RNAs-based biomarker network (long non-coding intergenic RNA-[lncRNA RP11-909B2.1], Homo sapiens microRNA-595 [hsa-miRNA-595], and L3MBTL1 mRNA), had high sensitivity and specificity for discriminating CRC from healthy controls and also from benign colorectal neoplasm. The data suggest that among these three RNAs, serum lncRNA RP11-909B2.1 could be a promising independent prognostic factors in CRC. The circulatory RNA based biomarker panel can act as potential biomarker for CRC diagnosis and prognosis.
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Affiliation(s)
- Nehal Samir
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt
| | - Marwa Matboli
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt
| | - Hanaa El-Tayeb
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt
| | - Ahmed El-Tawdi
- Department of General Surgery, Military Medical Academy, Cairo, Egypt
| | - Mohmed K Hassan
- Center for Genomics, Helmy Institute, Zewail City for Science and Technology, Giza, Egypt.,Biotechnology Program, Department of Zoology, Port Said Faculty of Science, Port Said, Egypt
| | - Amr Waly
- Center for Genomics, Helmy Institute, Zewail City for Science and Technology, Giza, Egypt
| | - Hesham A E El-Akkad
- Department of General Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed G Ramadan
- Department of Oncology Surgery, National Cancer Institute, Giza, Egypt
| | | | - Sherif El-Khamisy
- Center for Genomics, Helmy Institute, Zewail City for Science and Technology, Giza, Egypt
| | - Farid El-Asmar
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt
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14
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Zhang Q, Xin H, Fen T. Function of microRNA‑141 in human breast cancer through cytotoxic CD4+ T cells regulated by MAP4K4 expression. Mol Med Rep 2018; 17:7893-7901. [PMID: 29620289 DOI: 10.3892/mmr.2018.8814] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Accepted: 12/12/2017] [Indexed: 11/06/2022] Open
Abstract
The present study investigated the anti‑cancer effect of microRNA (miRNA)‑141 on apoptosis rate of breast cancer cells and the possible underlying mechanism. In patients with breast cancer, the expression of miRNA‑141 was downregulated. Overexpression of miRNA‑141 reduced breast cancer cell growth, inhibited the expression of cyclooxygenase‑2 (COX‑2), prostaglandin E2 (PGE2) and tumor necrosis factor (TNF)‑α, and increased the expression levels of interleukin (IL)‑10. However, downregulation of miRNA‑141 resulted in upregulation of COX‑2, PGE2 and TNF‑α expression levels, and an inhibition of IL‑10. Overexpression of miRNA‑141 suppressed mitogen‑activated protein kinase kinase kinase kinase 4 (MAP4K4) protein expression. Downregulation of miRNA‑141 markedly upregulated MAP4K4 protein expression in MCF‑7 cells. Promotion of MAP4K4 protein expression reduced the effects of miRNA‑141 on the toxicity of CD4+ T cells on breast cancer cells. The results of the present study indicated that miRNA‑141 may cause anti‑tumor effects in human breast cancer cells via cytotoxic CD4+ T cells.
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Affiliation(s)
- Qing Zhang
- Department of Breast Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, P.R. China
| | - Huang Xin
- Department of Breast Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, P.R. China
| | - Tang Fen
- Department of Breast Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, P.R. China
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15
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O'Brien SJ, Carter JV, Burton JF, Oxford BG, Schmidt MN, Hallion JC, Galandiuk S. The role of the miR-200 family in epithelial-mesenchymal transition in colorectal cancer: a systematic review. Int J Cancer 2018; 142:2501-2511. [DOI: 10.1002/ijc.31282] [Citation(s) in RCA: 68] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Revised: 01/16/2018] [Accepted: 01/23/2018] [Indexed: 12/12/2022]
Affiliation(s)
- Stephen J. O'Brien
- Price Institute of Surgical Research, The Hiram C. Polk Jr., M.D. Department of Surgery, University of Louisville; Louisville KY
| | - Jane V. Carter
- Price Institute of Surgical Research, The Hiram C. Polk Jr., M.D. Department of Surgery, University of Louisville; Louisville KY
- Department of Surgery; North Cumbria University Hospitals NHS Trust; Whitehaven Cumbria United Kingdom
| | - James F. Burton
- Price Institute of Surgical Research, The Hiram C. Polk Jr., M.D. Department of Surgery, University of Louisville; Louisville KY
| | - Brent G. Oxford
- Price Institute of Surgical Research, The Hiram C. Polk Jr., M.D. Department of Surgery, University of Louisville; Louisville KY
| | - Miranda N. Schmidt
- Price Institute of Surgical Research, The Hiram C. Polk Jr., M.D. Department of Surgery, University of Louisville; Louisville KY
| | - Jacob C. Hallion
- Price Institute of Surgical Research, The Hiram C. Polk Jr., M.D. Department of Surgery, University of Louisville; Louisville KY
| | - Susan Galandiuk
- Price Institute of Surgical Research, The Hiram C. Polk Jr., M.D. Department of Surgery, University of Louisville; Louisville KY
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16
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Yu J, Xu J, Zhao J, Zhang R. Serum miR-133b is a potential novel prognostic biomarker for colorectal cancer. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2017; 10:11673-11678. [PMID: 31966526 PMCID: PMC6966027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 12/28/2016] [Accepted: 01/25/2017] [Indexed: 06/10/2023]
Abstract
BACKGROUND Deregulation of microRNA-133b (miR-133b) has been demonstrated to contribute to the initiation and development of various cancers including colorectal cancer (CRC). However, the correlation between serum miR-133b levels and the prognosis of CRC remains elusive. METHODS A total of 98 CRC patients, 30 patients with precancerous polyps and 40 healthy volunteers were enrolled in this study. Quantitative real-time PCR (qRT-PCR) was performed to measure the serum miR-133b expression level in all the participants. The chi-square test was carried out to compare the categorical variables. Furthermore, survival analysis and cproportional hazards regression model were used to determine the prognostic significance of serum miR-133b in CRC. RESULTS Serum miR-133b level was progressively down-regulated from healthy controls, patients with precancerous polyps to CRC patients. CRC patients with higher clinical stage or lymph node metastasis had lower serum miR-133b levels. A positive correlation was found between decreased serum miR-133b levels and distant metastasis, lymph node metastasis and clinical stage. Additionally, CRC patients with high serum miR-203 levels had better 5 year overall survival and relapse free survival rates. Finally, low serum miR-133b level was demonstrated to be an independent risk factor for CRC. CONCLUSION These findings suggest that miR-133b might serve as a novel potential prognostic biomarker for CRC.
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Affiliation(s)
- Jie Yu
- Oncology Center, Qilu Hospital of Shandong UniversityQingdao, Shandong, P. R. China
| | - Jian Xu
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & InstituteLiaoning, P. R. China
| | - Jian Zhao
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & InstituteLiaoning, P. R. China
| | - Rui Zhang
- Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & InstituteLiaoning, P. R. China
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17
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Nie Y, Zhang P, Wang H, Zhuo Y, Chai Y, Yuan R. Ultrasensitive Electrochemiluminescence Biosensing Platform for Detection of Multiple Types of Biomarkers toward Identical Cancer on a Single Interface. Anal Chem 2017; 89:12821-12827. [DOI: 10.1021/acs.analchem.7b03240] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
- Yamin Nie
- Key Laboratory of Luminescent and Real-Time
Analytical Chemistry (Southwest University), Ministry of Education,
College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, People’s Republic of China
| | - Pu Zhang
- Key Laboratory of Luminescent and Real-Time
Analytical Chemistry (Southwest University), Ministry of Education,
College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, People’s Republic of China
| | - Haijun Wang
- Key Laboratory of Luminescent and Real-Time
Analytical Chemistry (Southwest University), Ministry of Education,
College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, People’s Republic of China
| | - Ying Zhuo
- Key Laboratory of Luminescent and Real-Time
Analytical Chemistry (Southwest University), Ministry of Education,
College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, People’s Republic of China
| | - Yaqin Chai
- Key Laboratory of Luminescent and Real-Time
Analytical Chemistry (Southwest University), Ministry of Education,
College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, People’s Republic of China
| | - Ruo Yuan
- Key Laboratory of Luminescent and Real-Time
Analytical Chemistry (Southwest University), Ministry of Education,
College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, People’s Republic of China
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18
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Li CF, Li YC, Jin JP, Yan ZK, Li DD. miR-938 promotes colorectal cancer cell proliferation via targeting tumor suppressor PHLPP2. Eur J Pharmacol 2017; 807:168-173. [PMID: 28433657 DOI: 10.1016/j.ejphar.2017.04.023] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2017] [Revised: 04/13/2017] [Accepted: 04/19/2017] [Indexed: 01/06/2023]
Abstract
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Although the development of therapy approaches, the outcome of CRC patients still is poor, understanding the biological mechanism of CRC progression is critical to improve the treatment strategies. miRNAs regulate CRC progression, we found miR-938 was upregulated in CRC tissues and cells, MTT assay, colony formation assay and soft agar growth assay suggested miR-938 overexpression promoted CRC cell proliferation, miR-938 knockdown inhibited CRC cell proliferation. Tumor suppressor PH domain Leucine-rich-repeats Protein Phosphatase 2 (PHLPP2) was a target of miR-938, miR-938 inhibited PHLPP2, luciferase activity assay suggested miR-938 directly bound to the 3'UTR of PHLPP2, meanwhile, we found miR-938 promoted c-Myc and Cyclin D1 expression, confirming miR-938 promoted CRC cell proliferation. Double knockdown of miR-938 and PHLPP2 promoted CRC cell proliferation, suggesting miR-938 promoted CRC cell proliferation by inhibiting PHLPP2.
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Affiliation(s)
- Chang-Feng Li
- Department of Endoscopy Center, China-Japan Union Hospital, Jilin University, Changchun 130033, China
| | - Yong-Chao Li
- Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
| | - Jing-Peng Jin
- Department of Endoscopy Center, China-Japan Union Hospital, Jilin University, Changchun 130033, China
| | - Zhen-Kun Yan
- Department of Endoscopy Center, China-Japan Union Hospital, Jilin University, Changchun 130033, China
| | - Dan-Dan Li
- Department of Endoscopy Center, China-Japan Union Hospital, Jilin University, Changchun 130033, China
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