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Jiang YK, Li W, Qiu YY, Yue M. Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer. World J Gastrointest Oncol 2024; 16:2318-2334. [PMID: 38994153 PMCID: PMC11236256 DOI: 10.4251/wjgo.v16.i6.2318] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 04/04/2024] [Accepted: 04/18/2024] [Indexed: 06/13/2024] Open
Abstract
Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance. Human epidermal growth factor receptor 2 (HER2) is one of the most important targets in targeted therapy for gastric cancer. Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer. The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified. However, monoclonal antibodies, due to their large molecular weight, inability to penetrate the blood-brain barrier, and drug resistance, lead to decreased therapeutic efficacy, so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer. Small-molecule tyrosine kinase inhibitors, such as lapatinib and pyrrotinib, have the advantages of small molecular weight, penetrating the blood-brain barrier and high oral bioavailability, and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future. Antibo-drug conjugate, such as T-DM1 and T-DXd, can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing, and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab. Therefore, after more detailed stratification of gastric cancer patients, various gastric cancer drugs targeting HER2 are expected to play a more significant role.
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Affiliation(s)
- Ya-Kun Jiang
- Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
| | - Wei Li
- Health Management Center, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
| | - Ying-Yang Qiu
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Meng Yue
- Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
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Li R, Wang J, Xie Z, Tian X, Hou J, Wang D, Qian H, Shen H, Xu W. CircUSP1 as a novel marker promotes gastric cancer progression via stabilizing HuR to upregulate USP1 and Vimentin. Oncogene 2024; 43:1033-1049. [PMID: 38366146 PMCID: PMC10978489 DOI: 10.1038/s41388-024-02968-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Revised: 02/01/2024] [Accepted: 02/05/2024] [Indexed: 02/18/2024]
Abstract
Circular RNAs (circRNAs) play a crucial role in regulating various tumors. However, their biological functions and mechanisms in gastric cancer (GC) have not been well understood. Here, we discovered a stable cytoplasmic circRNA named circUSP1 (hsa_circ_000613) in GC. CircUSP1 upregulation in GC tissues was correlated with tumor size and differentiation. We observed that circUSP1 promoted GC growth and metastasis. Mechanistically, circUSP1 mainly interacted with the RRM1 domain of an RNA-binding protein (RBP) called HuR, stabilizing its protein level by inhibiting β-TrCP-mediated ubiquitination degradation. The oncogenic properties of HuR mediated promotive effects of circUSP1 in GC progression. Moreover, we identified USP1 and Vimentin as downstream targets of HuR in post-transcriptional regulation, mediating the effects of circUSP1. The parent gene USP1 also enhanced the viability and mobility of GC cells. Additionally, tissue-derived circUSP1 could serve as an independent prognostic factor for GC, while plasma-derived circUSP1 showed promise as a diagnostic biomarker, outperforming conventional markers including serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA19-9). Our study highlights that circUSP1 promotes GC progression by binding to and stabilizing oncogenic HuR, thereby facilitating the upregulation of USP1 and Vimentin at the post-transcriptional level. These findings suggest that circUSP1 could be a potential therapeutic target and a diagnostic and prognostic biomarker for GC.
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Affiliation(s)
- Rong Li
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China
| | - Junyi Wang
- Centre of Clinical Laboratory, the First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu, 215006, China
| | - Zhenfan Xie
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China
| | - Xinyu Tian
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China
| | - Jie Hou
- Department of Clinical Laboratory, People's Hospital of Yangzhong City, 235 Yangzi Middle Road, Zhenjiang, Jiangsu, 212200, China
| | - Dongli Wang
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China
| | - Hui Qian
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China
| | - Han Shen
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China.
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China.
| | - Wenrong Xu
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, China.
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Shao X, Yin J, Wang D, Huang E, Zhang Y, Yin JC, Huang C, Wu H, Wu X. Case Report: A rare synchronous multiple gastric carcinoma achieved progression-free disease through NGS-guided serial treatment. Front Oncol 2023; 13:1195837. [PMID: 37496667 PMCID: PMC10366596 DOI: 10.3389/fonc.2023.1195837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 06/26/2023] [Indexed: 07/28/2023] Open
Abstract
Synchronous multiple gastric carcinoma (SMGC) is a rare condition characterized by the simultaneous occurrence of two or more primary malignant tumors in the stomach, each with its own distinct pathological morphology. SMGC differs from gastric metastases, which originate from primary gastric or non-gastric tumors. At present, the incidence of SMGC is low in China, with no established guidelines for standard treatment. Here, we report a rare case of advanced SMGC that achieved long-lasting clinical benefits through a treatment strategy informed by next-generation sequencing (NGS). Dynamically monitoring of the tumor and/or circulating cell-free DNA guided the patient's treatment sequentially. The patient received anti-HER2 therapy, followed by immunotherapy, pembrolizumab in combination with trastuzumab and chemotherapy, and ultimately underwent successful total gastrectomy. This case highlights a novel approach of utilizing liquid biopsy-based NGS to gain insights into disease progression and molecular response to NGS-guided treatment in SMGC patients.
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Affiliation(s)
- Xinyi Shao
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Jin Yin
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Di Wang
- Department of Medicine, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, China
| | - Erjiong Huang
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yini Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Jiani C. Yin
- Department of Medicine, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, China
| | - Chen Huang
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Hao Wu
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xiaoli Wu
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
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Impact of Selected Serum Factors on Metastatic Potential of Gastric Cancer Cells. Diagnostics (Basel) 2022; 12:diagnostics12030700. [PMID: 35328253 PMCID: PMC8946911 DOI: 10.3390/diagnostics12030700] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 02/24/2022] [Accepted: 03/09/2022] [Indexed: 02/06/2023] Open
Abstract
(1) Background: stromal-derived factor-1 (SDF-1/CXCL12), hepatocyte and vascular-endothelial growth factors (HGF and VEGF) have been shown to facilitate cell motility, proliferation and promote local tumor progression and metastatic spread. Recent research shows the important role of these cytokines in gastric cancer (GC) progression. (2) Methods: 21 gastric cancer patients and 19 healthy controls were included in the study. SDF-1, HGF and VEGF levels were evaluated in sera by ELISA. Patients and control sera were used to stimulate CRL-1739 GC cell line, and chemotaxis, adhesion and proliferation potential were assessed. (3) Results: Concentrations of SDF-1, HGF and VEGF were significantly higher in patients than in controls. Chemotaxis and adhesion assays revealed a significant response of GC cells to patients’ serum. Furthermore, significant relationships were seen between chemotactic/adhesion response and tumor stage. Serum from intestinal early GC patients produced significantly stronger chemotactic response when compared to patients with metastatic spread. In turn, serum from patients with distal metastases significantly increased the adhesion of GC cells when compared to sera from the patients with no distal metastases. We also observed that HGF strongly stimulated the proliferation of CRL-1739 cells. (4) Conclusions: We observed that the sera from GC patients, but also SDF-1, HGF and VEGF used alone, have a strong pro-metastatic effect on CRL-1739 cells. We also demonstrated that the concentration of these cytokines is specifically elevated in the sera of patients in an early stage of malignancy. Our results indicate that SDF-1, HGF and VEGF are very important molecules involved in gastric cancer progression.
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Zhao R, Li R, An T, Liu X. Conditional Cell Reprogramming in Modeling Digestive System Diseases. Front Cell Dev Biol 2021; 9:669756. [PMID: 34150763 PMCID: PMC8211013 DOI: 10.3389/fcell.2021.669756] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 04/27/2021] [Indexed: 12/12/2022] Open
Abstract
Digestive diseases have become an important source of morbidity and mortality. The considerable financial and health burdens caused by digestive diseases confirm the importance of extensive research to better understand and treat these diseases. The development of reliable preclinical models is essential for understanding the pathogenesis of digestive diseases and developing treatment and prevention methods. However, traditional established cell lines and animal models still have many limitations in the study of the digestive system. Conditional reprogramming (CR) cell culture is a newly developed primary technology that uses irradiated Swiss-3T3-J2 mouse fibroblast cells and the Rho-associated kinase (ROCK) inhibitor Y-27632 to rapidly and efficiently generate many cells from diseased and normal tissues. CR cells (CRCs) can be reprogrammed to maintain a highly proliferative state and recapitulate the histological and genomic features of the original tissue. Moreover, after removing these conditions, the phenotype was completely reversible. Therefore, CR technology may represent an ideal model to study digestive system diseases, to test drug sensitivity, to perform gene profile analysis, and to undertake xenograft research and regenerative medicine. Indeed, together with organoid cultures, CR technology has been recognized as one of the key new technologies by NIH precision oncology and also used for NCI human cancer model initiatives (HCMI) program with ATCC. In this article, we review studies that use CR technology to conduct research on diseases of the digestive system.
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Affiliation(s)
- Ruihua Zhao
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Rui Li
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Tianqi An
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xuefeng Liu
- Department of Pathology, Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC, United States.,Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, United States.,Departments of Pathology and Urology, The Ohio State University School of Medicine, Columbus, OH, United States.,James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
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Du R, Wang X, Ma L, Larcher LM, Tang H, Zhou H, Chen C, Wang T. Adverse reactions of targeted therapy in cancer patients: a retrospective study of hospital medical data in China. BMC Cancer 2021; 21:206. [PMID: 33639888 PMCID: PMC7916285 DOI: 10.1186/s12885-021-07946-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 02/21/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The adverse reactions (ADRs) of targeted therapy were closely associated with treatment response, clinical outcome, quality of life (QoL) of patients with cancer. However, few studies presented the correlation between ADRs of targeted therapy and treatment effects among cancer patients. This study was to explore the characteristics of ADRs with targeted therapy and the prognosis of cancer patients based on the clinical data. METHODS A retrospective secondary data analysis was conducted within an ADR data set including 2703 patients with targeted therapy from three Henan medical centers of China between January 2018 and December 2019. The significance was evaluated with chi-square test between groups with or without ADRs. Univariate and multivariate logistic regression with backward stepwise method were applied to assess the difference of pathological characteristics in patients with cancer. Using the univariate Cox regression method, the actuarial probability of overall survival was performed to compare the clinical outcomes between these two groups. RESULTS A total of 485 patients were enrolled in this study. Of all patients, 61.0% (n = 296) occurred ADRs including skin damage, fatigue, mucosal damage, hypertension and gastrointestinal discomfort as the top 5 complications during the target therapy. And 62.1% of ADRs were mild to moderate, more than half of the ADRs occurred within one month, 68.6% ADRs lasted more than one month. Older patients (P = 0.022) and patients with lower education level (P = 0.036), more than 2 comorbidities (P = 0.021), longer medication time (P = 0.022), drug combination (P = 0.033) and intravenous administration (P = 0.019) were more likely to have ADRs. Those with ADRs were more likely to stop taking (P = 0.000), change (P = 0.000), adjust (P = 0.000), or not take the medicine on time (P = 0.000). The number of patients with recurrence (P = 0.000) and metastasis (P = 0.006) were statistically significant difference between ADRs and non-ADRs group. And the patients were significantly poor prognosis in ADRs groups compared with non-ADRs group. CONCLUSION The high incidence of ADRs would affect the treatment and prognosis of patients with cancer. We should pay more attention to these ADRs and develop effective management strategies.
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Affiliation(s)
- Ruofei Du
- The College of Nursing and Health of Zhengzhou University, Zhengzhou, 450001 China
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
- School of Medical Sciences, Zhengzhou University, Zhengzhou, 450001 China
| | - Xin Wang
- The College of Nursing and Health of Zhengzhou University, Zhengzhou, 450001 China
| | - Lixia Ma
- School of Statistics, Henan University of Economics and Law, Zhengzhou, 450046 China
| | - Leon M. Larcher
- Centre for Comparative Genomics, Murdoch University, Perth, WA 6150 Australia
| | - Han Tang
- The College of Nursing and Health of Zhengzhou University, Zhengzhou, 450001 China
| | - Huiyue Zhou
- The College of Nursing and Health of Zhengzhou University, Zhengzhou, 450001 China
| | - Changying Chen
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
| | - Tao Wang
- The College of Nursing and Health of Zhengzhou University, Zhengzhou, 450001 China
- Centre for Comparative Genomics, Murdoch University, Perth, WA 6150 Australia
- Hebi People’s Hospital, Hebi, 458030 China
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Abstract
BACKGROUND This study aimed to investigate the expression level of X-linked 4 (BEX4) in patients with gastric cancer (GC) and to investigate the prognostic significance of BEX4. METHODS The mRNA expression of BEX4 was analyzed using the Cancer Genome Atlas (TCGA) datasets. The relationship between the expression of BEX4 and GC patient survival was assessed using a Kaplan-Meier plot and Log Rank test. Multivariate cox regression analysis was used to evaluate prognostic factor. The diagnostic value of BEX4 expression in GC tissue was determined through receiver operating characteristic (ROC) curve analysis. Gene set enrichment analysis (GSEA) was used to explore BEX-4 related signaling pathways in GC. Furthermore, the Human Protein Atlas (HPA) database and GSE62254 dataset were used for further validation. RESULTS BEX4 was expressed at lower level in GC tissues than normal gastric tissues. The lower expression of BEX4 was also validated at protein level in HPA database. The area under the ROC curve for BEX4 expression in normal gastric tissue and GC was 0.791, which presented modest diagnostic value. Kaplan-Meier survival analysis revealed that patients in low BEX4 expression group had a worse prognosis than those with high BEX4 expression (P = .009). Multivariate analysis showed that BEX4 is an independent risk factor for overall survival both in TCGA and GSE62254 (P = .0142, .013, respectively). GSEA identified that the expression of BEX4 was related to DNA replication, RNA polymerase, cell cycle, and P53 signaling pathway. CONCLUSION BEX4 is expressed at low levels in GC. BEX4 expression independently predicted poor OS for GC. It is a promising independent molecular predictor for the diagnosis and prognosis of GC.
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Ouyang J, Song F, Li H, Yang R, Huang H. miR-126 targeting GOLPH3 inhibits the epithelial-mesenchymal transition of gastric cancer BGC-823 cells and reduces cell invasion. Eur J Histochem 2020; 64. [PMID: 33131267 PMCID: PMC7649674 DOI: 10.4081/ejh.2020.3168] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 10/11/2020] [Indexed: 12/20/2022] Open
Abstract
The incidence and mortality of gastric cancer have been increasing in recent years. MiR-126 and target genes have been studied in gastric cancer, but their studies with Golgi phosphoprotein 3 (GOLPH3) and related pathways in gastric cancer are rarely reported. In the present study, we aimed to investigate the interaction between the miR-126 and GOLPH3in the progression of gastric cancer. In this study, we revealed the role of miR-126-GOLPH3 axis into regulating the progression of epithelial-mesenchymal transition (EMT) in BGC-823 cell model. Firstly, tumor tissues and adjacent normal tissues were collected from 45 patients with gastric cancer. We found the expression of miR-126 in human tumor tissue was significantly lower than in normal tissue using reverse transcription-polymerase chain reaction (RT-PCR). But the GOLPH3 expression was opposite by the detection of immunohistochemistry, RT-PCR and Western blot. Moreover, we predicted miR-126 targeting GOLPH3 by bioinformatics and confirmed the interaction using luciferase reporter gene system; miR-126 inhibited the proliferation, invasion and EMT progression in BGC-823 cells through overexpressing miR-126; miR-126 negative regulated GOLPH3 expression by overexpressing and interfering miR-126. Finally, we found GOLPH3 could promote proliferation using MTT assay, invasion using Transwell, and EMT progression by inhibiting the expression of E-cadherin, inducing vimentin and N-cadherin in BGC-823 cells. Our results demonstrated that miR-126 inhibits proliferative and invasive ability as well as EMT progression by targeting GOLPH3. This study may provide a new field of vision for targeted treatment of gastric cancer.
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Affiliation(s)
- Jiancai Ouyang
- Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou.
| | - Fuhu Song
- Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou.
| | - He Li
- Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou.
| | - Rui Yang
- Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou.
| | - Haicheng Huang
- Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou.
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Yang L, Zhang S, Guo K, Huang H, Qi S, Yao J, Zhang Z. miR-125a restrains cell migration and invasion by targeting STAT3 in gastric cancer cells. Onco Targets Ther 2018; 12:205-215. [PMID: 30636883 PMCID: PMC6309784 DOI: 10.2147/ott.s168454] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Recently, many microRNAs have been found to be involved in the cancer progression including miR-125a. However, the underlying mechanisms of miR-125a in gastric cancer (GC) remain to be completely elucidated. OBJECTIVE The study was to investigate the functional role of miR-125a and the expression relevance of signal transducer and activator of transcription 3 (STAT3) and hyaluronan synthase 1 (HAS1). METHOD CCK-8 assay, scratch wound healing and transwell assay were conducted to identify the functional role of miR-125a in GC. In addition, using bioinformatics analysis, the target regulation relationship was found in STAT3 and miR-125a. To confirm the relationship, luciferase reporter assay was performed. More importantly, quantitative polymerase chain reaction and western blot assay were carried out to determine the association among miR-125a, STAT3 and HAS1 in GC cells. RESULTS Overexpressed miR-125a inhibited the migration and invasion of GC cells through scratch wound healing and transwell assay, and its knockdown displayed adverse effects, but the viability of GC cells did not show significant difference using CCK-8 assay. In addition, we identified that the knockdown of STAT3 or HAS1 remarkably suppressed the migration and invasion abilities of GC cells. Using bioinformatics analysis, miRTar, in particular, indicated that the 3'-untranslated region of STAT3 binds to miR-125a with a high score. Subsequently, we also verified that STAT3 was a target of miR-125a via luciferase reporter assay. Furthermore, we found that upregulated miR-125a expression could conspicuously constrain STAT3 expression at both protein and mRNA levels in MKN45 and NCI-N87 cells using quantitative polymerase chain reaction and Western blot assay, but no significant difference had been found in SGC 7901 cells. To further identify the regulatory relationship between miR-125a and STAT3, downregulation of miR-125a in MKN45 and NCI-N87 cells was carried out, which showed that the protein and mRNA expression levels of STAT3 were declined in two cell lines. Finally, we observed that upregulated miR-125a could lead to the decrease of HAS1 at protein and mRNA levels, whereas its knockdown revealed opposite effects. Meanwhile, we noticed that overexpression of STAT3 could induce the escalation of HAS1 at protein and mRNA expression levels and its knockdown exhibited the adverse outcomes. CONCLUSION These findings indicated that miR-125a may control the HAS1 expression in GC progression by targeting STAT3, which is likely to facilitate a better understanding of the regulation mechanisms of miR-125a in GC.
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Affiliation(s)
- Liu Yang
- Department of Cancer Biotherapy Center, Hubei Cancer Hospital, Wuhan, Hubei 430079, China
| | - Shuguang Zhang
- Department of Clinical Laboratory, Liaocheng People's Hospital, Liaocheng, Shandong 252000, China
| | - Kai Guo
- Department of Gastroenterology, The 161th Hospital of PLA, Wuhan, Hubei 430010, China
| | - Hu Huang
- Department of Oncology, The 161th Hospital of PLA, Wuhan, Hubei 430010, China
| | - Shuai Qi
- Department of Pharmacy, The 161th Hospital of PLA, Wuhan, Hubei 430010, China
| | - Jie Yao
- Department of Urological Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China,
| | - Zhihong Zhang
- Department of Oncology, Gong'an County People's Hospital, Jingzhou, Hubei 434000, China,
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Zhou S, Xu B, Qi L, Zhu D, Liu B, Wei J. Next-generation sequencing reveals mutational accordance between cell-free DNA from plasma, malignant pleural effusion and ascites and directs targeted therapy in a gastric cancer patient. Cancer Biol Ther 2018; 20:15-20. [PMID: 30118648 PMCID: PMC6343684 DOI: 10.1080/15384047.2018.1504720] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Cell-free DNA (cfDNA) has been a research hotspot in molecular tumor profiling. In advanced gastric cancer patients, malignant pleural effusion (MPE) and ascites provide a wealth of tumor cells that can be investigated. Here we conducted next-generation sequencing (NGS) on matched cfDNA from plasma, MPE and ascites from a stage-IV gastric cancer patient to identify potential therapeutic targets. In all three samples, we detected an amplification in the cellular-mesenchymal to epithelial transition factor (MET) gene, a truncation mutation in SMAD3 (p.R368X), and four ataxia telangiectasia-mutated gene (ATM) variants, including a missense mutation (p.E2351A), an in-frame deletion (p.NPAVIM2353delinsK), a frame-shift deletion (p.D1758fs) and an ATM- BPI fold containing family B member 1 (BPIFB1) gene fusion. In contrast, we detected amplification of TEK only in malignant ascites. The patient was subjected to Crizotinib to counter MET amplification. Our study demonstrates high accordance in mutational spectra of matched cfDNA from plasma, MPE and ascites, and suggests that it is feasible to utilize these tumor sources in clinical decision-making.
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Affiliation(s)
- Shujuan Zhou
- a Department of Oncology, The Comprehensive Cancer Centre of Drum Tower Hospital , Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University , Nanjing , China
| | - Bo Xu
- a Department of Oncology, The Comprehensive Cancer Centre of Drum Tower Hospital , Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University , Nanjing , China
| | - Liang Qi
- a Department of Oncology, The Comprehensive Cancer Centre of Drum Tower Hospital , Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University , Nanjing , China
| | - Dongqin Zhu
- b Nanjing Geneseeq Technology Inc ., Nanjing , Jiangsu , China
| | - Baorui Liu
- a Department of Oncology, The Comprehensive Cancer Centre of Drum Tower Hospital , Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University , Nanjing , China
| | - Jia Wei
- a Department of Oncology, The Comprehensive Cancer Centre of Drum Tower Hospital , Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University , Nanjing , China
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Zhang X, Wang W, Li P, Wang X, Ni K. High TREM2 expression correlates with poor prognosis in gastric cancer. Hum Pathol 2018; 72:91-99. [DOI: 10.1016/j.humpath.2017.10.026] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2017] [Revised: 10/18/2017] [Accepted: 10/20/2017] [Indexed: 12/16/2022]
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