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RHPN1-AS1 通过海绵吸附 miR-6884-5p 从而释放 TOP2A mRNA 促进卵巢癌发生。

RHPN1‑AS1 promotes ovarian carcinogenesis by sponging miR‑6884‑5p thus releasing TOP2A mRNA.

机构信息

Department of Gynaecology and Obstetrics, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, P.R. China.

出版信息

Oncol Rep. 2021 Oct;46(4). doi: 10.3892/or.2021.8172. Epub 2021 Aug 20.

Abstract

Ovarian cancer, a severe lethal gynecological malignancy, is characterized by both high morbidity and mortality. Long noncoding RNAs (lncRNAs) have recently caused extensive concern due to their regulatory function in various human tumors. There are a mounting number of lncRNAs that are in extreme need of research, serving as biomarkers for diagnosis and therapy for ovarian cancer. In the present study, RT‑qPCR was employed to detect how Rhophilin Rho GTPase binding protein 1 antisense RNA1 (RHPN1‑AS1), miR‑6884‑5p and DNA topoisomerase IIα (TOP2A) are expressed in ovarian cancer tissues or cell lines. BrdU, MTT, colony formation and cell adhesion assays, caspase‑3 activity, flow cytometry and wound healing assay were employed to assess cell proliferation, viability, colony number, adhesion, apoptosis and migration in ovarian cancer, respectively. RHPN1‑AS1 was determined to be enriched in ovarian cancer tissues and cell lines. Silencing of RHPN1‑AS1 was reported to increase cell apoptosis and impair cell proliferation, viability, colony number, adhesion and migration . Furthermore, RHPN1‑AS1 was able to sponge miR‑6884‑5p which directly targets TOP2A in ovarian cancer. Notably, silencing of RHPN1‑AS1 functionally reversed the oncogenic effect induced by the miR‑6884‑5p inhibitor, while the miR‑6884‑5p inhibitor markedly restored the inhibition of ovarian carcinogenesis modulated by silencing TOP2A in ovarian cancer. RHPN1‑AS1 was found to promote ovarian carcinogenesis via sponging miR‑6884‑5p thus releasing TOP2A, and RHPN1‑AS1 may act as a promising biomarker for the prognosis and therapy of ovarian cancer.

摘要

卵巢癌是一种严重的致命妇科恶性肿瘤,其发病率和死亡率都很高。长链非编码 RNA(lncRNA)因其在各种人类肿瘤中的调节功能而引起了广泛关注。有大量的 lncRNA 急需研究,它们可以作为卵巢癌诊断和治疗的标志物。在本研究中,采用 RT-qPCR 检测卵巢癌组织或细胞系中 Rhophilin Rho GTPase 结合蛋白 1 反义 RNA1(RHPN1-AS1)、miR-6884-5p 和 DNA 拓扑异构酶 IIα(TOP2A)的表达。BrdU、MTT、集落形成和细胞黏附试验、caspase-3 活性、流式细胞术和划痕愈合试验分别用于评估卵巢癌细胞增殖、活力、集落数、黏附、凋亡和迁移。结果表明,RHPN1-AS1 在卵巢癌组织和细胞系中富集。沉默 RHPN1-AS1 可增加细胞凋亡,抑制细胞增殖、活力、集落数、黏附、迁移。此外,RHPN1-AS1 能够吸附 miR-6884-5p,miR-6884-5p 可直接靶向 TOP2A。沉默 RHPN1-AS1 可逆转 miR-6884-5p 抑制剂诱导的致癌作用,而 miR-6884-5p 抑制剂则可明显恢复沉默 TOP2A 对卵巢癌发生的抑制作用。RHPN1-AS1 通过吸附 miR-6884-5p 释放 TOP2A 促进卵巢癌发生,RHPN1-AS1 可能成为卵巢癌预后和治疗的有希望的标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc7/8424490/052769a750dc/or-46-04-8172-g00.jpg

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