Chen Shuo, Wang Li-Li, Sun Kai-Xuan, Liu Yao, Guan Xue, Zong Zhi-Hong, Zhao Yang
Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Key laboratory for Major Obstetric Diseases of Guangdong Province, and Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institute in Guangdong Province, Guangzhou, China.
Department of Gynecology, the First Affiliated Hospital of China Medical University, Shenyang, China.
Cell Physiol Biochem. 2018;47(4):1578-1588. doi: 10.1159/000490931. Epub 2018 Jun 27.
BACKGROUND/AIMS: Prostate cancer gene expression marker 1 (PCGEM1) is a long noncoding RNA (lncRNA) and is well known as a promoter in prostate cancer and osteoarthritis synoviocytes. However, the role PCGEM1 plays in epithelial ovarian cancer is unknown.
PCGEM1 expression was examined in epithelial ovarian cancer and normal ovarian tissues using reverse transcription-PCR. Ovarian cancer cell phenotypes and genotypes were examined after PCGEM1 overexpression or downregulation in vitro; besides, the effects of PCGEM1 overexpression was also examined in vivo.
PCGEM1 expression level was higher in epithelial ovarian cancer tissues than in normal ovarian tissues and was positively associated with differentiation (Well vs. Mod/Poor). Upregulation of PCGEM1 induced cancer cell proliferation, migration, and invasion, but decreased cell apoptosis through upregulating RhoA, YAP (Yes-associated protein), MMP2 (matrix metalloproteinase 2), Bcl-xL, and P70S6K expression; while PCGEM1 downregulation had the opposite effect. The nude mouse xenograft assay demonstrated that PCGEM1 overexpression promoted tumor growth. Furthermore, silencing RhoA expression reversed the effect of PCGEM1 and significantly inhibited RhoA, YAP, MMP2, Bcl-xL, and P70S6K protein expression.
In conclusion, we suggest that PCGEM1 may be an inducer in epithelial ovarian cancer tumorigenesis and progression by upregulating RhoA and the subsequent expression of YAP, P70S6K, MMP2, and Bcl-xL.
背景/目的:前列腺癌基因表达标志物1(PCGEM1)是一种长链非编码RNA(lncRNA),在前列腺癌和骨关节炎滑膜细胞中作为启动子而广为人知。然而,PCGEM1在上皮性卵巢癌中所起的作用尚不清楚。
采用逆转录聚合酶链反应检测PCGEM1在上皮性卵巢癌组织和正常卵巢组织中的表达。在体外对PCGEM1进行过表达或下调后,检测卵巢癌细胞的表型和基因型;此外,还在体内检测了PCGEM1过表达的影响。
PCGEM1在上皮性卵巢癌组织中的表达水平高于正常卵巢组织,且与分化程度(高分化vs.中/低分化)呈正相关。PCGEM1的上调诱导癌细胞增殖、迁移和侵袭,但通过上调RhoA、YAP(Yes相关蛋白)、MMP2(基质金属蛋白酶2)、Bcl-xL和P70S6K的表达降低细胞凋亡;而PCGEM1的下调则产生相反的效果。裸鼠异种移植试验表明,PCGEM1过表达促进肿瘤生长。此外,沉默RhoA表达可逆转PCGEM1的作用,并显著抑制RhoA、YAP、MMP2、Bcl-xL和P70S6K蛋白的表达。
总之,我们认为PCGEM1可能通过上调RhoA以及随后YAP、P70S6K、MMP2和Bcl-xL的表达,成为上皮性卵巢癌肿瘤发生和进展的诱导因子。