Long non-coding RNA LINC00858 aggravates the oncogenic phenotypes of ovarian cancer cells through miR-134-5p/RAD18 signa

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GYNECOLOGIC ONCOLOGY

Long non‑coding RNA LINC00858 aggravates the oncogenic phenotypes of ovarian cancer cells through miR‑134‑5p/RAD18 signaling Heng Xue1 · Zhihui Wu1 · Dongdong Rao1 · Bimin Zhuo1 · Qingquan Chen2  Received: 19 March 2020 / Accepted: 28 July 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Purpose  Ovarian cancer is a common gynecological cancer. Herein, we focused on the function and probable mechanisms of LINC00858 in ovarian cancer. Methods  Real-time quantitative polymerase chain reaction (RT-qPCR) was employed for detecting the expression of LINC00858, miR-134-5p and RAD18 E3 ubiquitin protein ligase (RAD18). Cell proliferation, migration, invasion, epithelialmesenchymal transition (EMT) and apoptosis were detected by cell counting kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), transwell, terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) and western bolt experiments, as appropriate. Interplays between LINC00858, miR-134-5p and RAD18 were detected by RNA immunoprecipitation (RIP), RNA pull down and luciferase reporter assays. Results  LINC00858 were up-regulated in ovarian cancer tissues and cells, and its expression was elevated in advanced samples compared to early ones. Knocking down LINC00858 inhibited cell proliferation, motility and EMT, but accelerated cell apoptosis in ovarian cancer. Moreover, could be sponged by LINC00858 sponged miR-134-5p to enhance RAD18 expression in ovarian cancer. Also, silenced RAD18 could also restrain oncogenic behaviors of ovarian cancer cells. Rescue experiments showed that overexpressing RAD18 reversed the effects caused by knocking down LINC00858 on cellular processes. Conclusion  LINC00858 sequestered miR-134-5p to elevate RAD18 expression, resulting in aggravated development of ovarian cancer. This might provide promising targets for treating patients with ovarian cancer. Keywords  LINC00858 · miR-134-5p · RAD18 · Ovarian cancer Abbreviations LINC00858 Long intergenic non-protein coding RNA 858 RAD18 RAD18 E3 ubiquitin protein ligase ncRNAs Non-coding RNAs lncRNAs Long non-coding RNAs Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s0040​4-020-05722​-z) contains supplementary material, which is available to authorized users. * Qingquan Chen [email protected] 1



Department of Laboratory Medicine, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou 350001, Fujian, China



Department of Laboratory Medicine, Fujian Medical University, 88 Jiaotong Road, Fuzhou 350004, Fujian, China

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ceRNAs Competing endogenous RNAs miRNAs MicroRNAs mRNA Messenger RNA ATCC​ American type culture collection RPMI Roswell Park Memorial Institute FBS Fetal bovine serum RT-qPCR Real-time quantitative polymerase chain reaction CCK-8 Cell counting kit-8 EdU 5-Ethynyl-2′-deoxyuridine TdT Terminal deoxynucleotidyl transferase TUNEL DUTP Nick-End Labeling SDS-PAGE Sulphate–polyacrylamide gel electr