Shen Fei, Cai Wen-Song, Feng Zhe, Li Jiang-Lin, Chen Ji-Wei, Cao Jie, Xu Bo
Department of General Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, 1 Panfu Road, Yuexiu District, Guangzhou, 510180, People's Republic of China.
Tumour Biol. 2015 Mar;36(3):1913-21. doi: 10.1007/s13277-014-2794-z. Epub 2014 Nov 19.
MicroRNAs (miRNAs) have emerged as important regulators that potentially play critical roles in cancer cell biological processes. Previous studies have shown that miR-492 plays an important role in cell tumorigenesis in multiple kinds of human cancer cells. However, the underlying mechanisms of this microRNA in breast cancer remain largely unknown. In the present study, we investigated miR-492's role in cell proliferation of breast cancer. MiR-492 expression was markedly upregulated in breast cancer tissues and breast cancer cells. Overexpression of miR-492 promoted the proliferation and anchorage-independent growth of breast cancer cells. Bioinformatics analysis further revealed sex-determining region Y-box 7 (SOX7), a putative tumor suppressor, as a potential target of miR-492. Data from luciferase reporter assays showed that miR-492 directly binds to the 3'-untranslated region (3'-UTR) of SOX7 messenger RNA (mRNA) and repressed expression at both transcriptional and translational levels. Ectopic expression of miR-492 led to downregulation of SOX7 protein, which resulted in the upregulation of cyclin D1 and c-Myc. In functional assays, SOX7 silenced in miR-492-in-transfected ZR-75-30 cells has positive effect to promote cell proliferation, suggesting that direct SOX7 downregulation is required for miR-492-induced cell proliferation and cell cycle of breast cancer. In sum, these results suggest that miR-492 represents a potential onco-miR and participates in breast cancer carcinogenesis by suppressing SOX7 expression.
微小RNA(miRNA)已成为重要的调节因子,可能在癌细胞生物学过程中发挥关键作用。先前的研究表明,miR-492在多种人类癌细胞的细胞肿瘤发生中起重要作用。然而,这种微小RNA在乳腺癌中的潜在机制仍 largely unknown。在本研究中,我们调查了miR-492在乳腺癌细胞增殖中的作用。miR-492在乳腺癌组织和乳腺癌细胞中明显上调。miR-492的过表达促进了乳腺癌细胞的增殖和非锚定依赖性生长。生物信息学分析进一步揭示了性别决定区Y盒7(SOX7),一种假定的肿瘤抑制因子,是miR-492的潜在靶点。荧光素酶报告基因检测数据表明,miR-492直接与SOX7信使核糖核酸(mRNA)的3'-非翻译区(3'-UTR)结合,并在转录和翻译水平上抑制其表达。miR-492的异位表达导致SOX7蛋白下调,进而导致细胞周期蛋白D1和c-Myc上调。在功能试验中,在miR-492转染的ZR-75-30细胞中沉默SOX7对促进细胞增殖有积极作用,表明直接下调SOX7是miR-492诱导乳腺癌细胞增殖和细胞周期所必需的。总之,这些结果表明,miR-492是一种潜在的致癌miRNA,通过抑制SOX7表达参与乳腺癌的发生。