Deng Boya, Zhang Yi, Zhang Siyang, Wen Fang, Miao Yuan, Guo Kejun
Department of Gynecology, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China.
Central Laboratory, China Medical University, Shenyang, 110001, People's Republic of China.
Tumour Biol. 2015 Sep;36(10):8065-73. doi: 10.1007/s13277-015-3483-2. Epub 2015 May 15.
MicroRNAs (miRNAs) are a class of small noncoding RNAs that play important roles in tumorigenesis and tumor progression through regulation of gene expression. Earlier, miR-142-3p was shown to decreased in cervical cancer cells; here; we explore the biological functional role of miR-142-3p and underlying mechanism in cervical cancer cells. We first detected the expression of miR-142-3p in six human cervical cancer cell lines and chose HeLa and SiHa cells for functional studies. By gain and loss of function experiments, we showed that overexpression of miR142-3p resulted in downregulation of Frizzled7 receptor (FZD7) and inhibited proliferation and invasion in HeLa and SiHa cells, whereas miR142-3p inhibitor-transfected cells showed reduced FZD7 expression and increased invasion capacity. In addition, we demonstrated that FZD7 was a direct target of miR-142-3p by dual luciferase assay and Western blot analysis. Overexpression of FZD7 expression was able to reverse the inhibitory effects induced by miR-142-3p. Taken together, miR-142-3p functions tumor suppressive effects in cell proliferation and invasion in cervical cancer cells, suggesting a potential therapeutic approach for cervical cancer.
微小RNA(miRNA)是一类小的非编码RNA,其通过调控基因表达在肿瘤发生和肿瘤进展中发挥重要作用。早期研究表明,miR-142-3p在宫颈癌细胞中表达降低;在此,我们探究miR-142-3p在宫颈癌细胞中的生物学功能作用及潜在机制。我们首先检测了六种人宫颈癌细胞系中miR-142-3p的表达,并选择HeLa和SiHa细胞进行功能研究。通过功能获得和缺失实验,我们发现miR-142-3p的过表达导致卷曲蛋白7受体(FZD7)表达下调,并抑制HeLa和SiHa细胞的增殖和侵袭,而转染miR-142-3p抑制剂的细胞FZD7表达降低,侵袭能力增强。此外,我们通过双荧光素酶报告基因检测和蛋白质印迹分析证明FZD7是miR-142-3p的直接靶点。FZD7表达的过表达能够逆转miR-142-3p诱导的抑制作用。综上所述,miR-142-3p在宫颈癌细胞的增殖和侵袭中发挥肿瘤抑制作用,提示其可能成为宫颈癌的一种潜在治疗方法。