Department of Gynecology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310051, China.
Department of Gynecologic Oncology, Women's Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310006, China.
Sci Rep. 2018 Feb 13;8(1):2876. doi: 10.1038/s41598-018-21164-9.
The roles of long non-coding RNAs (lncRNAs), a class of long non-protein-coding RNAs, in the tumorigenesis of ovarian epithelial cells remain unknown. In this study, we discovered that the expression of long intergenic non-coding RNA 1088 (LINC01088) was clearly reduced in benign epithelial ovarian tumor tissues compared to matched normal ovarian tissues. This was shown by global cDNA gene chip scanning and real-time qPCR, and validated in 42 clinical specimens. Furthermore, we found that LINC01088 inhibited the growth of ovarian cancer xenografts in nude mice. Correlation analysis between LINC01088 and mircoRNAs (miRNAs) conducted using primary clinical samples and RNA co-precipitation experiments revealed that miR-24-1-5p was one of the targets of LINC01088. Overexpression of miR-24-1-5p facilitated cell proliferation both in vitro and in vivo, however, LINC01088 could partially reverse the cell proliferation induced by miR-24-1-5p. Finally, we demonstrated that p21 activated kinase 4 (PAK4) was one of the downstream key targets of miR-24-1-5p by luciferase reporter assay and Western blotting; and our results showed a remarkable decrease in cell proliferation after overexpression of PAK4. We conclude that LINC01088 might function as a tumor suppressor, inhibiting the tumorigenesis of ovarian epithelial cells through LINC01088/ miR-24-1-5p/ PAK4 axis.
长非编码 RNA(lncRNAs)是一类长非蛋白编码 RNA,其在卵巢上皮细胞肿瘤发生中的作用尚不清楚。在本研究中,我们发现长基因间非编码 RNA 1088(LINC01088)在良性上皮性卵巢肿瘤组织中的表达明显低于配对的正常卵巢组织。这通过全基因芯片扫描和实时 qPCR 显示,并在 42 个临床标本中得到验证。此外,我们发现 LINC01088 抑制了裸鼠卵巢癌异种移植物的生长。使用原发性临床样本进行的 LINC01088 与 microRNAs(miRNAs)之间的相关分析和 RNA 共沉淀实验表明,miR-24-1-5p 是 LINC01088 的靶标之一。miR-24-1-5p 的过表达促进了体外和体内细胞的增殖,但 LINC01088 可以部分逆转 miR-24-1-5p 诱导的细胞增殖。最后,我们通过荧光素酶报告基因检测和 Western blot 证明 p21 激活激酶 4(PAK4)是 miR-24-1-5p 的下游关键靶标之一;并且我们的结果表明过表达 PAK4 后细胞增殖明显减少。我们得出结论,LINC01088 可能作为肿瘤抑制因子发挥作用,通过 LINC01088/miR-24-1-5p/PAK4 轴抑制卵巢上皮细胞的肿瘤发生。