Shi Haijuan, Shen Huimin, Xu Juan, Zhao Shanshan, Yao Shuzhong, Jiang Nan
The Second Affiliated Hospital of Guangxi Medical UniversityGuangxi, P. R. China.
The First Affiliated Hospital, Sun Yat-sen UniversityGuangzhou 510080, Guangdong, P. R. China.
Am J Transl Res. 2018 Mar 15;10(3):866-874. eCollection 2018.
MicroRNAs (miRNAs) are a class of naturally occurring, small, non-coding RNAs that target protein-coding mRNAs at the post-transcriptional level and participate in various biological processes. Our previous studies suggested that miR-143-3p functions as a tumor suppressor and has a role in the progression of ovarian cancer, in part through the regulation of the tumor promoter. In this study, we found that the mRNA expression level of miR-143-3p was significantly decreased in ovarian cancer tissues, in comparison with normal ovarian tissues by high-throughput miRNA profiling and quantitative RT-PCR. Secondly, we indicated that the up-regulation of miR-143-3p in the ovarian cancer cell lines SKOV3, ES2, and OVCAR3 significantly reduced their proliferation, migration, and invasion. Furthermore, miR-143-3p inhibited the growth of ovarian tumors in a xenograft experiment. In addition, miR-143-3p down-regulated the expression of transforming growth factor (TGF)-β-activated kinase 1 (TAK1) in human ovarian cancer cells. Therefore, our study indicates that miR-143-3p inhibited the proliferation, migration, and invasion of ovarian cancer cells , as well as ovarian tumorigenesis . This inhibitory effect may target TAK1, suggesting a potential application of the miR-143-3p-TAK1 pathway in the clinical diagnosis and treatment of ovarian cancer.
微小RNA(miRNA)是一类天然存在的小的非编码RNA,它们在转录后水平靶向蛋白质编码mRNA,并参与各种生物学过程。我们之前的研究表明,miR-143-3p起到肿瘤抑制因子的作用,并且在卵巢癌进展中发挥作用,部分是通过对肿瘤促进因子的调控。在本研究中,通过高通量miRNA分析和定量逆转录PCR,我们发现与正常卵巢组织相比,miR-143-3p在卵巢癌组织中的mRNA表达水平显著降低。其次,我们指出在卵巢癌细胞系SKOV3、ES2和OVCAR3中miR-143-3p的上调显著降低了它们的增殖、迁移和侵袭能力。此外,在异种移植实验中miR-143-3p抑制了卵巢肿瘤的生长。另外,miR-143-3p下调了人卵巢癌细胞中转化生长因子(TGF)-β激活激酶1(TAK1)的表达。因此,我们的研究表明miR-143-3p抑制了卵巢癌细胞的增殖、迁移和侵袭以及卵巢肿瘤发生。这种抑制作用可能靶向TAK1,提示miR-143-3p-TAK1通路在卵巢癌临床诊断和治疗中的潜在应用。