Tao Fangfang, Tian Xinxin, Ruan Shanming, Shen Minhe, Zhang Zhiqian
Department of Immunology and Microbiology, Basic Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
Department of Biochemistry and Biophysics, Texas A&M AgriLife Research, Texas A&M University, College Station, Texas, USA.
FASEB J. 2018 Jun 6:fj201800495RR. doi: 10.1096/fj.201800495RR.
Accumulating evidence has indicated that microRNAs (miRNAs) play an important role in the occurrence and progression of ovarian cancer (OC). However, the function of miRNAs implicated in OC remains unclear. This study investigated the potential role of miR-211 in OC. Gene Expression Omnibus database analysis indicated that miR-211 expression was significantly down-regulated in OC tissues compared with normal specimens. In addition, miR-211 overexpression apparently inhibited proliferation, migration, xenograft growth, and induced apoptosis in HEY-T30 and SKOV3 cells. Moreover, PHF19, a component of the polycomb group of proteins, was found to be a direct target of miR-211 based on the luciferase reporter assay and Western blot analysis. Consistently, survival analysis indicated that high PHF19 expression was associated with shorter survival time in patients with OC. Importantly, silence of PHF19 reduced proliferation, induced cell cycle arrest, promoted apoptosis, suppressed migration, and inhibited xenograft growth in SKOV3 cells. Restoration of PHF19 expression markedly reversed the inhibitory effect of miR-211 on OC. Moreover, our results indicate that the long noncoding RNA MALAT1 could sponge miR-211 as a competing endogenous RNA and potentially up-regulate PHF19 expression, thus facilitating the OC progression. These findings suggest that the MALAT1/miR-211/PHF19 axis may act as a key mediator in OC and provide new insight into the prevention of this disease.-Tao, F., Tian, X., Ruan, S., Shen, M., Zhang, Z. miR-211 sponges lncRNA MALAT1 to suppress tumor growth and progression through inhibiting PHF19 in ovarian carcinoma.
越来越多的证据表明，微小RNA（miRNA）在卵巢癌（OC）的发生和发展中起重要作用。然而，与OC相关的miRNA的功能仍不清楚。本研究调查了miR-211在OC中的潜在作用。基因表达综合数据库分析表明，与正常标本相比，OC组织中miR-211的表达显著下调。此外，miR-211过表达明显抑制了HEY-T30和SKOV3细胞的增殖、迁移、异种移植生长，并诱导细胞凋亡。此外，基于荧光素酶报告基因检测和蛋白质免疫印迹分析，发现多梳蛋白家族的一个成员PHF19是miR-211的直接靶点。一致地，生存分析表明，OC患者中PHF19高表达与较短的生存时间相关。重要的是，沉默PHF19可降低SKOV3细胞的增殖，诱导细胞周期停滞，促进细胞凋亡，抑制迁移，并抑制异种移植生长。恢复PHF19表达可显著逆转miR-211对OC的抑制作用。此外，我们的结果表明，长链非编码RNA MALAT1可以作为竞争性内源RNA吸附miR-211，并可能上调PHF19的表达，从而促进OC的进展。这些发现表明，MALAT1/miR-211/PHF19轴可能是OC中的关键调节因子，并为该疾病的预防提供了新的见解。——陶，F.，田，X.，阮，S.，沈，M.，张，Z. miR-211通过抑制卵巢癌中的PHF19来吸附长链非编码RNA MALAT1以抑制肿瘤生长和进展
