Tumour suppressor properties of miR-15a and its regulatory effects on BCL2 and SOX2 proteins in colorectal carcinomas

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Objectives:In this study, we aimed to investigate the expression pattern, clinicopathological significance and tumour suppressive properties of miR-15a in patients with colorectal carcinomas.Methods:Tissue samples from 87 patients with primary colorectal carcinomas, 50 matched metastatic lymph node and 37 non-neoplastic colon (control) were prospectively recruited. The expression level of miR-15a was measured by quantitative real-time polymerase chain reaction. Restoration/overexpression of the miR-15a was achieved by exogenous transfection. Four colon cancer cell lines (SW480, CaCO2, SW48 and HCT116) and a non-cancer colon cell line (FHC) were also used for examining the miR-15a induced tumour suppression properties using various in-vitro and immunological assays.Results:Downregulation of miR-15a was noted in ˜ 62% of the colorectal carcinoma tissues and it was positively correlated with the presence of cancer recurrence in patients with colorectal carcinomas (p = 0.05). Also, these patients with low miR-15a expression showed relatively shorter survival time when compared to those with miR-15a overexpression. Following miR-15a exogenous overexpression, colon cancer cells showed reduced cell proliferation, low colony formation, less cell invasion properties and mitochondrial respiration when compared to control cells. In addition, BCL2 and SOX2 proteins showed a significant downregulation following miR-15a overexpression suggesting its regulatory role in cancer growth, apoptosis and stemness.Conclusion:This study has confirmed the tumour suppressor properties of miR-15a in colorectal cancers. Therefore, its modulation has potential implications in controlling various biological and pathogenic processes in colon carcinogenesis via targeting its downstream proteins such as BCL2 and SOX2.HighlightsDownregulation of miR-15a was noted with colon cancer cell lines and patients with colorectal adenocarcinomas.Expression levels of miR-15a was significantly altered with their matched metastatic lymph node tissues.MiR-15 exhibits tumour suppressive properties in-vitro via controlling cell growth and mitochondrial respiration.MiR-15a expresses its regulatory roles in cancer cell growth, apoptosis and stemness via BCL2 and SOX2 modulation.

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