Long Non-coding RNA PVT1-mediated MiR-543/SERPINI1 Axis Plays a Key Role in the Regulatory Mechanism of Ovarian Cancer

Overview

Journal Biosci Rep

Specialty Cell Biology

Date 2020 May 23

PMID 32441301

Citations 11

Authors

Chong Qu

Chunmei Dai

Yahua Guo

Rui Qin

Junbao Liu

Affiliations

Soon will be listed here.

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.

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References

Liu S, Yang J, Cao D, Shen K . Identification of differentially expressed long non-coding RNAs in human ovarian cancer cells with different metastatic potentials. Cancer Biol Med. 2014; 10(3):138-41. PMC: 3860336. DOI: 10.7497/j.issn.2095-3941.2013.03.003. View

Li S, Shan Y, Li X, Zhang C, Wei S, Dai S . lncRNA SNHG5 Modulates Endometrial Cancer Progression via the miR-25-3p/BTG2 Axis. J Oncol. 2019; 2019:7024675. PMC: 6925730. DOI: 10.1155/2019/7024675. View

Wang Z, Su M, Xiang B, Zhao K, Qin B . Circular RNA PVT1 promotes metastasis via miR-145 sponging in CRC. Biochem Biophys Res Commun. 2019; 512(4):716-722. DOI: 10.1016/j.bbrc.2019.03.121. View

Zhou M, Wang X, Shi H, Cheng L, Wang Z, Zhao H . Characterization of long non-coding RNA-associated ceRNA network to reveal potential prognostic lncRNA biomarkers in human ovarian cancer. Oncotarget. 2016; 7(11):12598-611. PMC: 4914307. DOI: 10.18632/oncotarget.7181. View

Matulonis U, Sood A, Fallowfield L, Howitt B, Sehouli J, Karlan B . Ovarian cancer. Nat Rev Dis Primers. 2016; 2:16061. PMC: 7290868. DOI: 10.1038/nrdp.2016.61. View

Trabert B, Tworoger S, OBrien K, Townsend M, Fortner R, Iversen E . The Risk of Ovarian Cancer Increases with an Increase in the Lifetime Number of Ovulatory Cycles: An Analysis from the Ovarian Cancer Cohort Consortium (OC3). Cancer Res. 2020; 80(5):1210-1218. PMC: 7056529. DOI: 10.1158/0008-5472.CAN-19-2850. View

Liu X, Gan L, Zhang J . miR-543 inhibites cervical cancer growth and metastasis by targeting TRPM7. Chem Biol Interact. 2019; 302:83-92. DOI: 10.1016/j.cbi.2019.01.036. View

Wang W, Zhou R, Wu Y, Liu Y, Su W, Xiong W . PVT1 Promotes Cancer Progression via MicroRNAs. Front Oncol. 2019; 9:609. PMC: 6644598. DOI: 10.3389/fonc.2019.00609. View

Song N, Liu H, Ma X, Zhang S . Placental growth factor promotes metastases of ovarian cancer through MiR-543-regulated MMP7. Cell Physiol Biochem. 2015; 37(3):1104-12. DOI: 10.1159/000430235. View

10.

Ong M, Cai W, Yuan Y, Leong H, Tan T, Mohammad A . 'Lnc'-ing Wnt in female reproductive cancers: therapeutic potential of long non-coding RNAs in Wnt signalling. Br J Pharmacol. 2017; 174(24):4684-4700. PMC: 5727316. DOI: 10.1111/bph.13958. View

11.

Cody N, Zietarska M, Filali-Mouhim A, Provencher D, Mes-Masson A, Tonin P . Influence of monolayer, spheroid, and tumor growth conditions on chromosome 3 gene expression in tumorigenic epithelial ovarian cancer cell lines. BMC Med Genomics. 2008; 1:34. PMC: 2519080. DOI: 10.1186/1755-8794-1-34. View

12.

Moore K, Colombo N, Scambia G, Kim B, Oaknin A, Friedlander M . Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2018; 379(26):2495-2505. DOI: 10.1056/NEJMoa1810858. View

13.

Yu Q, Zhang Z, He B, Wang H, Shi P, Li Y . MiR-543 functions as tumor suppressor in ovarian cancer by targeting TWIST1. J Biol Regul Homeost Agents. 2020; 34(1):101-110. DOI: 10.23812/19-567-A. View

14.

Yamanaka S, Olaru A, An F, Luvsanjav D, Jin Z, Agarwal R . MicroRNA-21 inhibits Serpini1, a gene with novel tumour suppressive effects in gastric cancer. Dig Liver Dis. 2012; 44(7):589-96. PMC: 3360813. DOI: 10.1016/j.dld.2012.02.016. View

15.

Yang G, Lu X, Yuan L . LncRNA: a link between RNA and cancer. Biochim Biophys Acta. 2014; 1839(11):1097-109. DOI: 10.1016/j.bbagrm.2014.08.012. View

16.

Valiente M, Obenauf A, Jin X, Chen Q, Zhang X, Lee D . Serpins promote cancer cell survival and vascular co-option in brain metastasis. Cell. 2014; 156(5):1002-16. PMC: 3988473. DOI: 10.1016/j.cell.2014.01.040. View

17.

Webb P, Jordan S . Epidemiology of epithelial ovarian cancer. Best Pract Res Clin Obstet Gynaecol. 2016; 41:3-14. DOI: 10.1016/j.bpobgyn.2016.08.006. View

18.

Doubeni C, Doubeni A, Myers A . Diagnosis and Management of Ovarian Cancer. Am Fam Physician. 2016; 93(11):937-44. View

19.

Chen P, Chang W, Chou R, Lai Y, Lin S, Chi C . Two non-homologous brain diseases-related genes, SERPINI1 and PDCD10, are tightly linked by an asymmetric bidirectional promoter in an evolutionarily conserved manner. BMC Mol Biol. 2007; 8:2. PMC: 1796892. DOI: 10.1186/1471-2199-8-2. View

20.

Chai Y, Liu J, Zhang Z, Liu L . HuR-regulated lncRNA NEAT1 stability in tumorigenesis and progression of ovarian cancer. Cancer Med. 2016; 5(7):1588-98. PMC: 4944886. DOI: 10.1002/cam4.710. View