Long non-coding RNA PVT1-mediated miR-543 /SERPINI1 axis plays a key role in the regulatory mechanism of ovarian cancer
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Chong Qu, Chunmei Dai, Yahua Guo, Rui Qin, Junbao Liu
Abstract
Purpose: To investigate the regulation mechanism of long non-coding RNA (IncRNA) plasmocytoma variant translocation 1 (PVT1) in ovarian cancer (OC). Methods: The levels of PVT1, miR-543, serpin peptidase inhibitor-clade I (neuroserpin)-member 1 (SERPINI1) in OC tissues and OVCAR-3, A2780, TOV-112D of OC cell lines were detected by qRT-PCR and Western Blot. Cell proliferation, migration, invasion, apoptosis and the regulatory relationship between genes and target genes were analyzed by MTT, Transwell, flow cytometry and dual luciferase report (DLR). The OC patients were followed up for 5 years to analyze the relationship between PVT1 and 5-year overall survival (OS). Results: In contrast to miR-543, PVT1 and SERPINI1 were highly expressed in OC tissues and cell lines, and high levels of PVT1 were significantly associated with lower 5-year OS of patients. Down-regulating PVT1 not only inhibited the malignant proliferation, migration and invasion of OC cells, but promoted cell apoptosis. PVT1 regulated miR-543 in a targeted manner, and its overexpression could attenuate the anti-cancer effect of miR-543 on OC cells. In addition, miR-543 also directly targeted SERPINI1, and miR-543 knockdown weakened the inhibitory effect of down-regulated SERPINI1 on OC progression. Furthermore, we found that PVT1 acted as a competitive endogenous RNA to sponge miR-543, thereby regulating the expression of SERPINI1. Conclusion: PVT1 can mediate the molecular mechanism of OC by miR-543/SERPINI1 axis regulatory network, which is a new therapeutic direction for OC.
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