Sathyanarayanan Anusha, Chandrasekaran Karthik Subramanian, Karunagaran Devarajan
Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, 600036, Tamil Nadu, India.
Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, 600036, Tamil Nadu, India.
Biochem Biophys Res Commun. 2016 Nov 25;480(4):528-533. doi: 10.1016/j.bbrc.2016.10.054. Epub 2016 Oct 18.
microRNAs (miRNAs) play significant roles in diverse biological processes and their deregulation is implicated in carcinogenesis. miR-146a executes tumour suppressive or oncogenic functions depending on the cancer type, but its effect on human cervical (CaCx) and colorectal (CRC) cancers have not been examined thus far. In this study, miR-146a exhibited high expression in CaCx but poor expression in CRC, in comparison to corresponding normal tissues. Nevertheless, ectopic expression of miR-146a inhibited proliferation in both CaCx and CRC cells and curbed their migration and invasion. When the expression of endogenous miR-146a was suppressed, proliferative, migratory and invasive capacities of CaCx and CRC cells increased, suggesting an anti-tumourigenic function for miR-146a. Re-expression of miR-146a down-regulated the expression of crucial signalling intermediates: CTNNB1, STAT3, RELA, CCND1 and SNAI1, and enhanced TP53 and CDH1 expression. Thus, the present study reveals a hitherto unknown tumour suppressive role for miR-146a providing a plausible mechanistic basis for it.
微小RNA(miRNA)在多种生物学过程中发挥着重要作用,其失调与癌症发生有关。miR-146a根据癌症类型发挥肿瘤抑制或致癌功能,但迄今为止,其对人类宫颈癌(CaCx)和结直肠癌(CRC)的影响尚未得到研究。在本研究中,与相应的正常组织相比,miR-146a在CaCx中高表达,而在CRC中低表达。然而,miR-146a的异位表达抑制了CaCx和CRC细胞的增殖,并抑制了它们的迁移和侵袭。当内源性miR-146a的表达被抑制时,CaCx和CRC细胞的增殖、迁移和侵袭能力增加,提示miR-146a具有抗肿瘤发生功能。miR-146a的重新表达下调了关键信号中间体CTNNB1、STAT3、RELA、CCND1和SNAI1的表达,并增强了TP53和CDH1的表达。因此,本研究揭示了miR-146a迄今为止未知的肿瘤抑制作用,并为其提供了合理的机制基础。