Long non-coding RNA PVT1-mediated miR-543/SERPINI1 axis plays a key role in the regulatory mechanism of ovarian cancer

Abstract

Purpose: To investigate the regulation mechanism of long non-coding RNA (lncRNA) plasmocytoma variant translocation 1 (PVT1) in ovarian cancer (OC). Methods: The levels of PVT1, microRNA (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 quantitative real-time PCR (qRT-PCR) and Western Blot (WB). Cell proliferation, migration, invasion, apoptosis and the regulatory relationship between genes and target genes were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Transwell, flow cytometry and dual luciferase reporter (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 with 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 anticancer 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.

lncRNA FDNCR promotes apoptosis of granulosa cells by targeting the miR-543-3p/DCN/TGF-β signaling pathway in Hu sheep

“… 37 lncRNAs PTV1 and PCAT6 act as ceRNAs to sponge miR-543 to regulate SERPINI1 and ZEB1 expression, respectively. 48 , 49 In the present study, we found that FDNCR sponged miR-543-3p to negatively regulate miR-543-3p function in GC proliferation and apoptosis. Alternatively, miR-543-3p promoted GC proliferation, which was consistent with previous studies.…”

LncRNAs in Ovarian Cancer Progression, Metastasis, and Main Pathways: ceRNA and Alternative Mechanisms

“…In numerous studies, lncRNA PVT1 (plasmacytoma variant translocation 1) was upregulated in OvCa cell lines and tissues and involved in the promotion of proliferation, migration, EMT, invasion, and metastasis of OvCa cells ( Table 2 ). It was shown that oncogenic PVT1 interacts with several tumor-suppressive miRNAs, such as miR-133a [ 164 ], miR-214 [ 165 ], miR-140 [ 166 ], and miR-543 [ 167 ]; also, inhibition of suppressor miRNAs is one of the modes to enhance the progression of OvCa. Direct binding of PVT1 to miR-133a was validated via transfections, qRT-PCR, and luciferase reporter assays [ 164 ].…”

“…PVT1 inhibited miR-140 as a miRNA sponge, while transcription of PVT1 was regulated by the transcription factor FOXO4 ( Table 2 ). The lncRNA PVT1 and predicted target SERPINI1 (serpin peptidase inhibitor-clade I (neuroserpin)-member 1) were upregulated in OvCa cell lines and tumor tissues, unlike the downregulated tumor-suppressive miR-543 [ 167 ]. A direct interaction was validated in the PVT1/miR-543/SERPINI1 axis via the dual-luciferase reporter assay [ 167 ].…”

“…Thus, the lncRNA PVT1 promotes OvCa progression through four described axes ( Table 2 ). The cited studies [ 164 , 165 , 166 , 167 ] showed that PVT1 was the most amplified gene in OvCa patients, and it was highly correlated with poor survival outcomes (progression-free and overall survivals), representing a novel perspective diagnostic and prognostic biomarker ( Table 2 ).…”

Mechanisms of Apoptosis-Related Long Non-coding RNAs in Ovarian Cancer

“…For example, CYTOR/LINC00152 acts as a ceRNA of miR-125b to upregulate an antiapoptotic protein MCL1 in A2780 and SKOV3 cells ( Chen et al, 2018 ). PVT1 suppresses apoptosis in OVACAR3 and TOV112D cells by inhibiting miR-543 and increasing a miR-543 target SERPIN1 ( Qu et al, 2020 ). In contrast, MEG3 promotes apoptosis in OVCAR8 and SKOV3 cells by sponging miR-205-5p ( Tao et al, 2020 ).…”