Department of General Surgery, Shandong University Qilu Hospital, Jinan, China.
Department of General Surgery, Shandong University Qilu Hospital, Jinan, China.
Biomed Pharmacother. 2017 Sep;93:1047-1054. doi: 10.1016/j.biopha.2017.07.030. Epub 2017 Jul 18.
Accumulating evidences have shown that microRNAs (miRNAs) are vital regulators and possess huge capabilities in post-transcriptional control. Although a large number of miRNAs have been identified to be dysregulated in human cancers especially in colon cancer, our understandings of the function of most miRNAs are still largely limited. In this study, we have demonstrated that miR-299-3p plays a critical role in suppressing colon carcinoma progression by targeting Vascular Endothelial Growth Factor A (VEGFA). We observed that miR-299-3p was down-regulated in colon carcinoma tissues and colon cancer cell lines. The level of miR-299-3p was significantly negatively correlated with that of VEGFA mRNA level in colon carcinoma. More importantly, the low level of miR-299-3p predicted poor prognosis of colon cancer patients. Functionally, overexpression of miR-299-3p inhibited the proliferation and invasion of colon carcinoma cells and suppressed the growth of colon cancer xenografts in nude mice. Luciferase reporter assays showed that miR-299-3p could target VEGFA 3' UTR. In addition, up-regulation of miR-299-3p decreased VEGFA expression both in vitro and in vivo, showing that miR-299-3p plays a suppressive effect on VEGFA via post-transcriptional control. However, ectopical expression of VEGFA could abrogate this effect and also abolish miR-299-3p-induced inhibition of cell proliferation and invasion. Taken together, our study provides evidences showing that miR-299-3p functions as a suppressor in colon cancer by targeting VEGFA, suggesting that miR-299-3p might serve as a novel target for colon cancer therapy.
越来越多的证据表明,microRNAs(miRNAs)是重要的调控因子,具有在后转录水平进行调控的巨大能力。虽然已经发现大量 miRNAs 在人类癌症中失调,尤其是在结肠癌中,但我们对大多数 miRNAs 的功能仍然知之甚少。在本研究中,我们通过靶向血管内皮生长因子 A(VEGFA)证明了 miR-299-3p 在抑制结肠癌进展中发挥关键作用。我们观察到 miR-299-3p 在结肠癌组织和结肠癌细胞系中下调。miR-299-3p 的水平与结肠癌中 VEGFA mRNA 水平显著负相关。更重要的是,miR-299-3p 水平低预示着结肠癌患者预后不良。功能上,过表达 miR-299-3p 抑制了结肠癌细胞的增殖和侵袭,并抑制了裸鼠结肠癌异种移植物的生长。荧光素酶报告基因检测表明,miR-299-3p 可以靶向 VEGFA 3'UTR。此外,体外和体内上调 miR-299-3p 均降低了 VEGFA 的表达,表明 miR-299-3p 通过转录后调控发挥对 VEGFA 的抑制作用。然而,外源性表达 VEGFA 可以消除这种作用,并消除 miR-299-3p 诱导的细胞增殖和侵袭抑制。总之,我们的研究提供了证据表明,miR-299-3p 通过靶向 VEGFA 作为结肠癌的抑制因子发挥作用,提示 miR-299-3p 可能成为结肠癌治疗的新靶点。