Liu Yao, Zong Zhi-Hong, Guan Xue, Wang Li-Li, Zhao Yang
Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang 100013, China.
Gene. 2017 Oct 30;633:42-47. doi: 10.1016/j.gene.2017.08.027. Epub 2017 Aug 31.
Ovarian carcinoma is one of the highest incidence of tumors in women, and the generation, development and prognosis of epithelial ovarian carcinoma (EOC) remains an open field of study. The role of long non-coding RNAs (lncRNAs) in epithelial ovarian carcinoma is an emerging area of research.
LncRNA PCA3 expression was determined in EOC and normal ovarian tissues by RT-PCR. Phenotypes indicative of tumor progression and aggressiveness, including cell proliferation, migration, invasion, and expression of related molecules, were analysed in EOC cell following knockdown of lncRNA PCA3 by transfection with small interfering RNA (siRNA).
Expression of lncRNA PCA3 in epithelial ovarian cancer tissues was higher than in normal ovarian tissue. We discovered that knockdown of lncRNA PCA3 in EOC cells by siRNA transfection significantly suppressed cell proliferation, migration, and invasion. Bioinformatic predictions and dual-luciferase reporter assays indicate that the 3'UTR of PCA3 has potential binding sites for miR-106b-5p. Knockdown of the lncRNA PCA3 by siRNA resulted in up-regulated miR-106b expression. In addition, knockdown of PCA3 also reduced protein expression of Ras homolog gene family member C (RhoC), Bcl/xl, P70 ribosomal S6 kinase (P70S6K), and Matrix metallopeptidase 2 (MMP2), which are regulated by miR-106b.
Research results show that lncRNA PCA3 may coordinate EOC tumorigenesis through disrupting miR-106b regulated gene expression. PCA3 may be a novel and important diagnostic biomarker and a valuable marker for prediction in the clinical care of epithelial ovarian carcinoma.
卵巢癌是女性中发病率最高的肿瘤之一，上皮性卵巢癌（EOC）的发生、发展及预后仍是一个有待深入研究的领域。长链非编码RNA（lncRNA）在上皮性卵巢癌中的作用是一个新兴的研究领域。
通过逆转录聚合酶链反应（RT-PCR）检测EOC组织和正常卵巢组织中lncRNA PCA3的表达。在用小干扰RNA（siRNA）转染敲低lncRNA PCA3后，分析EOC细胞中指示肿瘤进展和侵袭性的表型，包括细胞增殖、迁移、侵袭及相关分子的表达。
lncRNA PCA3在上皮性卵巢癌组织中的表达高于正常卵巢组织。我们发现，通过siRNA转染敲低EOC细胞中的lncRNA PCA3可显著抑制细胞增殖、迁移和侵袭。生物信息学预测和双荧光素酶报告基因检测表明，PCA3的3'非翻译区（UTR）具有与miR-106b-5p的潜在结合位点。通过siRNA敲低lncRNA PCA3导致miR-106b表达上调。此外，敲低PCA3还降低了受miR-106b调控的Ras同源基因家族成员C（RhoC）、Bcl/xl、P70核糖体S6激酶（P70S6K）和基质金属蛋白酶2（MMP2）的蛋白表达。
研究结果表明，lncRNA PCA3可能通过破坏miR-106b调控的基因表达来协调EOC的肿瘤发生。PCA3可能是一种新型且重要的诊断生物标志物，也是上皮性卵巢癌临床护理中预测的有价值标志物。
