Cancer Molecular Pathology, School of Medicine, Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia; School of Medical Science, Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia.
Cancer Molecular Pathology, School of Medicine, Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia.
Exp Cell Res. 2018 Sep 15;370(2):245-253. doi: 10.1016/j.yexcr.2018.06.025. Epub 2018 Jun 26.
In this study, we aimed to investigate the expression pattern, clinicopathological significance and tumour suppressive properties of miR-15a in patients with colorectal carcinomas.
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.
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.
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.
本研究旨在探讨 miR-15a 在结直肠癌患者中的表达模式、临床病理意义和肿瘤抑制特性。
前瞻性招募 87 例原发性结直肠癌患者、50 例匹配的转移性淋巴结和 37 例非肿瘤性结肠（对照）组织样本。通过定量实时聚合酶链反应测量 miR-15a 的表达水平。通过外源性转染实现 miR-15a 的恢复/过表达。还使用四种结肠癌细胞系（SW480、CaCO2、SW48 和 HCT116）和一种非癌性结肠细胞系（FHC），通过各种体外和免疫测定来检查 miR-15a 诱导的肿瘤抑制特性。
约 62%的结直肠癌组织中存在 miR-15a 的下调，并且与结直肠癌患者癌症复发的存在呈正相关（p=0.05）。此外，与 miR-15a 过表达的患者相比，这些 miR-15a 低表达的患者的生存时间相对较短。与对照细胞相比，外源性过表达 miR-15a 后，结肠癌细胞的增殖减少，集落形成减少，细胞侵袭能力降低，线粒体呼吸减少。此外，BCL2 和 SOX2 蛋白的表达水平在过表达 miR-15a 后显著下调，提示其在肿瘤生长、凋亡和干性方面的调节作用。
本研究证实了 miR-15a 在结直肠癌中的肿瘤抑制特性。因此，通过靶向其下游蛋白如 BCL2 和 SOX2 来调节 miR-15a 可能对控制结直肠癌发生过程中的各种生物学和发病机制具有潜在意义。
