Downregulation of miR-146a promotes cell migration in Helicobacter pylori-negative gastric cancer
| Autor: | Behzad Mansoori, Mehdi Yousefi, Pascal H.G. Duijf, Dariush Shanehbandi, Navid Shomali, Naghmeh Shirafkan, Elham Baghbani, Behzad Baradaran, Zohreh Babaloo, Mehri Ghasabi, Ali Mohammadi, Milad Asadi |
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| Přispěvatelé: | Shomali, Navid, Shirafkan, Naghmeh, Duijf, Pascal HG, Ghasabi, Mehri, Babaloo, Zohreh, Yousefi, Mehdi, Mansoori, Behzad, Asadi, Milad, Shanehbandi, Dariush, Baghbani, Elham, Mohammadi, Ali, Baradaran, Behzad |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Carcinogenesis Cell Survival Down-Regulation Apoptosis Helicobacter pylori-negative patients Biochemistry Metastasis 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cell Movement Stomach Neoplasms Cell Line Tumor Gene expression microRNA medicine Humans metastasis Neoplasm Metastasis Molecular Biology Aged Cell Proliferation Helicobacter pylori biology Oncogene miR‐146a gastric cancer apoptosis Cancer Cell migration Cell Biology Middle Aged biology.organism_classification medicine.disease Survival Analysis Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Female |
| Popis: | microRNAs (miRs) are short noncoding RNAs that post‐transcriptionally suppress gene expression. miR‐146a acts as an oncogene or a tumor suppressor in various cancers, including gastric cancer, but it is unclear what determines whether miR‐146a is oncogenic or tumor suppressive and the molecular mechanisms are still largely unknown. The aim of this study was to investigate the role of miR‐146a in gastric cancer, by focusing on its expression in patients who were negative for Helicobacter pylori and its reduced and increased expression effect in vitro. Twenty gastric cancer patients who were negative for H. pylori infection were selected and the expression levels of miRNA‐146a in these gastric tumors, in their matched normal gastric tissues and in gastric cancer cell lines with varying tumorigenic potential was measured. Further, the impact of increased and decreased miR-146a expression levels on the expression of predicted target genes, cell migration, viability, proliferation, and apoptosis was examined, respectively. Our results for the first time indicated that miR-146a is downregulated in H. pylori-negative gastric cancers and suggests that H. pylori infection determines whether miR-146a acts as an oncogene or tumor suppressor. The level of miR-146a expression inversely correlates with the tumorigenicity of three gastric cancer cell lines and low miR-146a expression predicts poor recurrence-free survival. It was also found that miR-146a reduces the expression levels of the prometastatic genes and suppresses MKN-45 cell migration. Functional studies showed that miR-146a acts as a tumor suppressor miR and identifies miR-146a as a candidate for antimetastatic miRNA replacement therapy for gastric cancer patients. Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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