Wen Aiping, Luo Le, Du Chengchao, Luo Xin
Department of Gynecology and Obstetrics, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.
Department of Gynecology and Obstetrics, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, P.R. China.
Exp Ther Med. 2021 Nov;22(5):1237. doi: 10.3892/etm.2021.10672. Epub 2021 Aug 31.
Ovarian cancer (OC) is the third commonest gynecological malignancy worldwide. The long non-coding (lnc)RNA microRNA (miR)155HG functions as an oncogene in different human cancers. However, the function and molecular mechanism of miR155HG in OC remain elusive. The present study indicated that the expression levels of miR155HG and tyrosinase-related protein 1 (TYRP1) were significantly increased, whereas that of miR155-5p was decreased in OC tissues and cells, as detected by real-time quantitative polymerase chain reaction. It was demonstrated that knockdown of miR155HG markedly inhibited OC cell viability, migration and invasion while promoting apoptosis, as indicated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound healing, Transwell and western blot assays. Mechanistically, it was revealed that miR155HG and TYRP1 were both targeted by miR-155-5p with complementary binding sites in the 3' untranslated region. A dual-luciferase reporter assay was used to confirm the targeting relationship between miR155HG, miR-155-5p and TYRP1. In addition, the interaction between miR155HG and miR-155-5p was further demonstrated by radioimmunoprecipitation and pull-down assays. In addition, feedback approaches determined that miR-155-5p inhibition or TYRP1 overexpression markedly reversed the inhibitory effects of miR155HG knockdown on OC cell viability, migration and invasion as well as weakened the promotive effect of miR155HG knockdown on OC cell apoptosis. Thus, miR155HG silencing inhibited the malignant biological behavior of OC cells by targeting the miR-155-5p/TYRP1 axis. The present study provides novel insights into the underlying mechanism of OC progression.
卵巢癌（OC）是全球第三常见的妇科恶性肿瘤。长链非编码（lnc）RNA微小RNA（miR）155HG在不同的人类癌症中发挥癌基因的作用。然而，miR155HG在OC中的功能和分子机制仍不清楚。本研究表明，通过实时定量聚合酶链反应检测发现，miR155HG和酪氨酸酶相关蛋白1（TYRP1）在OC组织和细胞中的表达水平显著升高，而miR155-5p的表达水平降低。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐、伤口愈合、Transwell和蛋白质印迹分析表明，敲低miR155HG可显著抑制OC细胞活力、迁移和侵袭，同时促进细胞凋亡。机制上，研究发现miR155HG和TYRP1在3'非翻译区均有与miR-155-5p互补的结合位点，二者均为miR-155-5p的靶标。采用双荧光素酶报告基因检测法证实了miR155HG、miR-155-5p和TYRP1之间的靶向关系。此外，放射免疫沉淀和下拉分析进一步证实了miR155HG与miR-155-5p之间的相互作用。此外，反馈方法确定，抑制miR-155-5p或过表达TYRP1可显著逆转敲低miR155HG对OC细胞活力、迁移和侵袭的抑制作用，并减弱敲低miR155HG对OC细胞凋亡的促进作用。因此，miR155HG沉默通过靶向miR-155-5p/TYRP1轴抑制OC细胞的恶性生物学行为。本研究为OC进展的潜在机制提供了新的见解。
