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

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    Author(s)
    Gopalan, Vinod
    Ebrahimi, Faeza
    Islam, Farhadul
    Vider, Jelena
    Qallandar, Omel Baneen
    Pillai, Suja
    Lu, Cu-Tai
    Lam, Alfred King-yin
    Griffith University Author(s)
    Lam, Alfred K.
    Gopalan, Vinod
    Islam, Farhad
    Year published
    2018
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    Abstract
    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 ...
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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.
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    Journal Title
    Experimental Cell Research
    Volume
    370
    Issue
    2
    DOI
    https://doi.org/10.1016/j.yexcr.2018.06.025
    Copyright Statement
    © 2018 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
    Subject
    Biochemistry and cell biology
    Biochemistry and cell biology not elsewhere classified
    Clinical sciences
    Publication URI
    http://hdl.handle.net/10072/382481
    Collection
    • Journal articles

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