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.
Highlights
Ovarian cancer (OC) is the eighth leading cause of cancer-related deaths worldwide, and its risk increases with the number of ovulation cycles in women [1,2]
Plasmocytoma variant translocation 1 (PVT1), which is the focus of this study, is often used as a carcinogen to induce the aggravation of the disease in cancer, and can regulate the tumor microenvironment through the negative regulation of miRNA
SERPINI1 mediates the mechanism of brain metastasis, in which pathological changes promote the survival of tumor cells and vascular combination, and is closely associated with the brain recurrence of primary tumors, suggesting that SERPINI1 may be a threat to human health in most cases [22]
Summary
Ovarian cancer (OC) is the eighth leading cause of cancer-related deaths worldwide, and its risk increases with the number of ovulation cycles in women [1,2]. The lncRNA family plays a role in the development of gynecological tumors such as breast cancer, cervical cancer and endometrial cancer, but participates in the pathological mechanism of OC [9,10,11,12]. Through Starbase, we predicted the potential target sites between PVT1 and miR-543, of which the latter serves as a tumor inhibitor in cervical cancer while playing a malignant role in promoting tumor growth and metastasis in prostate cancer [16,17]. MiR-543 shows a low level in OC tissues and cells, which can play an anticancer role in OC by targeting TWIST1, and can be regulated by placental growth factors and silenced to promote MMP7-mediated tumor invasion in OC [18,19]. SERPINI1 mediates the mechanism of brain metastasis, in which pathological changes promote the survival of tumor cells and vascular combination, and is closely associated with the brain recurrence of primary tumors, suggesting that SERPINI1 may be a threat to human health in most cases [22]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
