Li Bin, Chen Peng, Chang Yanxiang, Qi Jingpeng, Fu Hui, Guo Huifang
Department of Oncology, The First Affiliated Hospital of Xi'an Medical University, Shaanxi, Xi'an 710077, China.
Institution of Basic Medical Science, Xi'an Medical University, Shaanxi, Xi'an 710021, China; School of Life Sciences, Northwest University, Shaanxi, Xi'an 710069, China.
Biochem Biophys Res Commun. 2016 Sep 16;478(2):739-45. doi: 10.1016/j.bbrc.2016.08.018. Epub 2016 Aug 4.
Colorectal cancer (CRC) is the third most common cancer worldwide, with high morbidity. MicroRNAs (miRNAs) are endogenous small RNAs that play important roles in regulating multiple biological and pathologic processes. The differential expression of miRNAs in CRC was first reported in 2003. Accumulated evidence indicates that lethal-7a (let-7a, miRNA) generally functions as a tumor suppressor in several human cancers. However, the role of let-7a in human colon cancer remains unclear. The aim of this study was to investigate the biological functions of let-7a and its potential role in colon cancer. We first discovered that let-7a level was significantly decreased in colon cancer tissues and cell lines (HT-29, HCT-116, LoVo, SW480, and SW620). To explore the effects of let-7a on colon cancer, let-7a over-expressed HCT-116 and SW620 cells were constructed. Further studies demonstrated that over-expressed let-7a could remarkably inhibit HCT-116 and SW620 cell growth and metastasis by directly down-regulating Rhotekin (RTKN). When RTKN was reintroduced into let-7a mimic transfected HCT-116 or SW620 cells, the inhibition effects of let-7a on colon cancer cell growth and metastasis were markedly reversed. In conclusion, our research shows that let-7a can inhibit tumor cell growth and metastasis by directly targeting RTKN in human colon cancer.
结直肠癌(CRC)是全球第三大常见癌症,发病率很高。微小RNA(miRNA)是内源性小RNA,在调节多种生物学和病理过程中发挥重要作用。miRNA在结直肠癌中的差异表达于2003年首次报道。越来越多的证据表明,致死-7a(let-7a,miRNA)在几种人类癌症中通常起着肿瘤抑制作用。然而,let-7a在人类结肠癌中的作用仍不清楚。本研究的目的是探讨let-7a的生物学功能及其在结肠癌中的潜在作用。我们首先发现,let-7a水平在结肠癌组织和细胞系(HT-29、HCT-116、LoVo、SW480和SW620)中显著降低。为了探究let-7a对结肠癌的影响,构建了过表达let-7a的HCT-116和SW620细胞。进一步研究表明,过表达的let-7a可通过直接下调Rhotekin(RTKN)显著抑制HCT-116和SW620细胞的生长和转移。当将RTKN重新导入转染了let-7a模拟物的HCT-116或SW620细胞中时,let-7a对结肠癌细胞生长和转移的抑制作用明显逆转。总之,我们的研究表明,let-7a可通过直接靶向人类结肠癌中的RTKN来抑制肿瘤细胞的生长和转移。