College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, Zhejiang 310018, China.
Library of Zhejiang Sci-Tech University, Hangzhou, Zhejiang 310018, China.
Protein Pept Lett. 2022;29(10):829-838. doi: 10.2174/0929866529666220704122019.
Ovarian carcinoma (OC) is one of the most common malignancies of the female reproductive organs, with a low survival rate primarily due to the lack of effective methods for early diagnosis and prognosis.
In this article, our motivation is to explore the lncRNA-related network mechanisms involved in the pathogenesis of OC.
Public lncRNAs and mRNA expression datasets for OC were collected from the Gene Expression Omnibus (GEO) database. By integrated bioinformatics analysis, we constructed a UCA1-miRNA-mRNA network. We studied lncRNA-related molecular modulation mechanism in ovarian cancer cells based on MTT assay, dual luciferase reporter gene assays, quantitative realtime PCR, and western blotting.
UCA1 was higher in ovarian tumor tissues and cells than normal tissues and cells. It was demonstrated in this study that knockdown of UCA1 inhibited ovarian cancer cell viability, which a miR-99b-3p inhibitor could reverse in vitro. Further, UCA1 was shown to regulate the expression of SRPK1 by directly binding to miR-99b-3p.
These results suggest that UCA1 functions as an oncogene in ovarian cancer. Inhibition of UCA1/miR-99b-3p/SRPK1 axis may become a novel target for treating ovarian cancer.
卵巢癌（OC）是女性生殖器官最常见的恶性肿瘤之一，其生存率低主要是因为缺乏有效的早期诊断和预后方法。
本文旨在探讨 lncRNA 相关网络机制在 OC 发病机制中的作用。
从基因表达综合数据库（GEO）中收集 OC 的公共 lncRNA 和 mRNA 表达数据集。通过综合生物信息学分析，构建了 UCA1-miRNA-mRNA 网络。我们基于 MTT 检测、双荧光素酶报告基因检测、实时定量 PCR 和 Western blot 研究了 lncRNA 相关分子在卵巢癌细胞中的调控机制。
UCA1 在卵巢肿瘤组织和细胞中的表达高于正常组织和细胞。本研究表明，敲低 UCA1 可抑制卵巢癌细胞的活力，而 miR-99b-3p 抑制剂可在体外逆转这种作用。此外，UCA1 通过直接结合 miR-99b-3p 来调节 SRPK1 的表达。
这些结果表明，UCA1 在卵巢癌中作为癌基因发挥作用。抑制 UCA1/miR-99b-3p/SRPK1 轴可能成为治疗卵巢癌的新靶点。
