Acta Biochim Biophys Sin (Shanghai). 2022 Feb 25;54(2):209-219. doi: 10.3724/abbs.2022002.
Ovarian cancer (OC) is a fatal gynecological malignancy that is difficult to diagnose at early stages. Various long non-coding RNAs (lncRNAs) are aberrantly expressed in OC and exert regulatory effects on OC; however, the underlying mechanism requires in-depth investigation. This work is designed to explore the molecular regulatory axis of a newly identified lncRNA in OC, that is, lncRNA RP5-1148A21.3 (lncRP5). RT-qPCR shows lncRP5 is significantly upregulated in OC patients and cell lines, and it is mainly located in the cytoplasm of OC cells. The results of CCK-8, colony formation, and transwell assays demonstrate that overexpression of lncRP5 greatly contributes to malignant behaviors of OC cells, while inhibition of lncRP5 shows the opposite effects. Moreover, the binding relationship between lncRP5 and miR-545-5p is predicted by bioinformatics and is further verified by luciferase assay. Functionally, the regulatory effects of lncRP5 and miR-545-3p are negatively related; miR-545-5p serves as a tumor suppressor in OC. Further studies demonstrate that PTP4A1 is the target gene of miR-545-5p. Overexpression of PTP4A1 abrogates the inhibitory function of miR-545-5p on OC cell growth and metastasis. The lncRP5/miR-545-5p/PTP4A1 axis is subsequently demonstrated in vivo, and knockdown of lncRP5 notably inhibits tumor growth. This study provides a novel regulatory mechanism of OC, which may contribute to the diagnosis and therapy of OC.
卵巢癌(OC)是一种致命的妇科恶性肿瘤,早期诊断困难。各种长链非编码 RNA(lncRNA)在 OC 中异常表达,并对 OC 发挥调节作用;然而,其潜在机制需要深入研究。本工作旨在探讨新鉴定的 lncRNA 在 OC 中的分子调节轴,即 lncRNA RP5-1148A21.3(lncRP5)。RT-qPCR 显示 lncRP5 在 OC 患者和细胞系中显著上调,主要位于 OC 细胞的细胞质中。CCK-8、集落形成和 Transwell 分析的结果表明,lncRP5 的过表达极大地促进了 OC 细胞的恶性行为,而抑制 lncRP5 则表现出相反的效果。此外,生物信息学预测了 lncRP5 与 miR-545-5p 的结合关系,并通过荧光素酶报告基因实验进一步验证。功能上,lncRP5 和 miR-545-3p 的调节作用呈负相关;miR-545-5p 在 OC 中作为一种肿瘤抑制因子。进一步的研究表明,PTP4A1 是 miR-545-5p 的靶基因。PTP4A1 的过表达可消除 miR-545-5p 对 OC 细胞生长和转移的抑制作用。随后在体内验证了 lncRP5/miR-545-5p/PTP4A1 轴,敲低 lncRP5 显著抑制肿瘤生长。本研究为 OC 提供了一种新的调控机制,可能有助于 OC 的诊断和治疗。