Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Research Article

circEPSTI1 Acts as a ceRNA to Regulate the Progression of Osteosarcoma

Author(s): Xinyu Tan, Duxun Tan, Haomiao Li, Ye Lin, Zhishen Wen and Canjun Zeng*

Volume 20, Issue 4, 2020

Page: [288 - 294] Pages: 7

DOI: 10.2174/1568009619666191107140948

Price: $65

Abstract

Background: Recent studies have reported the vital roles of circular RNAs (circRNAs) in tumor progression. However, the function and expression profile of most circRNAs in osteosarcoma remain unclear.

Methods: We examined the expression of circEPSTI1, a circRNA, in 50 paired adjacent normal tissues and osteosarcoma tissues by qRT-PCR. Then, we further explored the function of circEPSTI1 in osteosarcoma progression in vitro and in vivo. For example, cell proliferation and migration were examined. Some experiments were performed to explore the regulatory function of circEPSTI1 in miRNA and to investigate the potential role of circEPSTI1 in osteosarcoma.

Results: We found that circEPSTI1 was significantly upregulated in osteosarcoma. Inhibition of circEPSTI1 suppressed the osteosarcoma cancer cell proliferation and migration in vitro. Dual luciferase reporter assay showed that circEPSTI1 and MCL1 (myeloid cell leukaemia 1) could bind to miR-892b and that MCL1 and circEPSTI1 were targets of miR-892b.

Conclusion: Thus, the circEPSTI1-miR-892b-MCL1 axis affected osteosarcoma progression through the miRNA sponging mechanism. circEPSTI1 may serve as a target and biomarker for osteosarcoma treatment.

Keywords: circEPSTI1, circular RNAs, miR-892b, MCL1, competitive endogenous RNAs, osteosarcoma.

Graphical Abstract

[1]
Isakoff, M.S.; Bielack, S.S.; Meltzer, P.; Gorlick, R. Osteosarcoma: Current treatment and a collaborative pathway to success. J. Clin. Oncol., 2015, 33(27), 3029-3035.
[http://dx.doi.org/10.1200/JCO.2014.59.4895] [PMID: 26304877]
[2]
Kansara, M.; Teng, M.W.; Smyth, M.J.; Thomas, D.M. Translational biology of osteosarcoma. Nat. Rev. Cancer, 2014, 14(11), 722-735.
[http://dx.doi.org/10.1038/nrc3838] [PMID: 25319867]
[3]
Tang, W.; Fu, K.; Sun, H.; Rong, D.; Wang, H.; Cao, H. CircRNA microarray profiling identifies a novel circulating biomarker for detection of gastric cancer. Mol. Cancer, 2018, 17(1), 137.
[http://dx.doi.org/10.1186/s12943-018-0888-8] [PMID: 30236115]
[4]
Tan, S.; Sun, D.; Pu, W.; Gou, Q.; Guo, C.; Gong, Y.; Li, J.; Wei, Y.Q.; Liu, L.; Zhao, Y.; Peng, Y. Circular RNA F-circEA-2a derived from EML4-ALK fusion gene promotes cell migration and invasion in non-small cell lung cancer. Mol. Cancer, 2018, 17(1), 138.
[http://dx.doi.org/10.1186/s12943-018-0887-9] [PMID: 30236141]
[5]
Salmena, L.; Poliseno, L.; Tay, Y.; Kats, L.; Pandolfi, P.P. A ceRNA hypothesis: The rosetta stone of a hidden RNA language? Cell, 2011, 146(3), 353-358.
[http://dx.doi.org/10.1016/j.cell.2011.07.014] [PMID: 21802130]
[6]
Karreth, F.A.; Pandolfi, P.P. ceRNA cross-talk in cancer: When ce-bling rivalries go awry. Cancer Discov., 2013, 3(10), 1113-1121.
[http://dx.doi.org/10.1158/2159-8290.CD-13-0202] [PMID: 24072616]
[7]
Tay, Y.; Rinn, J.; Pandolfi, P.P. The multilayered complexity of ceRNA crosstalk and competition. Nature, 2014, 505(7483), 344-352.
[http://dx.doi.org/10.1038/nature12986] [PMID: 24429633]
[8]
Memczak, S.; Jens, M.; Elefsinioti, A.; Torti, F.; Krueger, J.; Rybak, A.; Maier, L.; Mackowiak, S.D.; Gregersen, L.H.; Munschauer, M.; Loewer, A.; Ziebold, U.; Landthaler, M.; Kocks, C.; le Noble, F.; Rajewsky, N. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature, 2013, 495(7441), 333-338.
[http://dx.doi.org/10.1038/nature11928] [PMID: 23446348]
[9]
Hansen, T.B.; Jensen, T.I.; Clausen, B.H.; Bramsen, J.B.; Finsen, B.; Damgaard, C.K.; Kjems, J. Natural RNA circles function as efficient microRNA sponges. Nature, 2013, 495(7441), 384-388.
[http://dx.doi.org/10.1038/nature11993] [PMID: 23446346]
[10]
Chen, B.; Wei, W.; Huang, X.; Xie, X.; Kong, Y.; Dai, D.; Yang, L.; Wang, J.; Tang, H.; Xie, X. circEPSTI1 as a prognostic marker and mediator of triple-negative breast cancer progression. Theranostics, 2018, 8(14), 4003-4015.
[http://dx.doi.org/10.7150/thno.24106] [PMID: 30083277]
[11]
Lam, L.T.; Lu, X.; Zhang, H.; Lesniewski, R.; Rosenberg, S.; Semizarov, D. A microRNA screen to identify modulators of sensitivity to BCL2 inhibitor ABT-263 (navitoclax). Mol. Cancer Ther., 2010, 9(11), 2943-2950.
[http://dx.doi.org/10.1158/1535-7163.MCT-10-0427] [PMID: 20829195]
[12]
Gill, J.; Ahluwalia, M.K.; Geller, D.; Gorlick, R. New targets and approaches in osteosarcoma. Pharmacol. Ther., 2013, 137(1), 89-99.
[http://dx.doi.org/10.1016/j.pharmthera.2012.09.003] [PMID: 22983152]
[13]
Kun-Peng, Z.; Xiao-Long, M.; Lei, Z.; Chun-Lin, Z.; Jian-Ping, H.; Tai-Cheng, Z. Screening circular RNA related to chemotherapeutic resistance in osteosarcoma by RNA sequencing. Epigenomics, 2018, 10(10), 1327-1346.
[http://dx.doi.org/10.2217/epi-2018-0023] [PMID: 30191736]
[14]
Kun-Peng, Z.; Chun-Lin, Z.; Jian-Ping, H.; Lei, Z. A novel circulating HSA_circ_0081001 act as a potential biomarker for diagnosis and prognosis of osteosarcoma. Int. J. Biol. Sci., 2018, 14(11), 1513-1520.
[http://dx.doi.org/10.7150/ijbs.27523] [PMID: 30263004]
[15]
Kun-Peng, Z.; Xiao-Long, M.; Chun-Lin, Z. Overexpressed circPVT1, a potential new circular RNA biomarker, contributes to doxorubicin and cisplatin resistance of osteosarcoma cells by regulating ABCB1. Int. J. Biol. Sci., 2018, 14(3), 321-330.
[http://dx.doi.org/10.7150/ijbs.24360] [PMID: 29559849]
[16]
Wang, Y.; Hou, J.; He, D.; Sun, M.; Zhang, P.; Yu, Y.; Chen, Y. The emerging function and mechanism of ceRNAs in cancer. Trends Genet., 2016, 32(4), 211-224.
[http://dx.doi.org/10.1016/j.tig.2016.02.001] [PMID: 26922301]
[17]
Li, X.; Yang, L.; Chen, L.L. The Biogenesis, functions, and challenges of circular RNAs. Mol. Cell, 2018, 71(3), 428-442.
[http://dx.doi.org/10.1016/j.molcel.2018.06.034] [PMID: 30057200]
[18]
Xie, F.; Li, Y.; Wang, M.; Huang, C.; Tao, D.; Zheng, F.; Zhang, H.; Zeng, F.; Xiao, X.; Jiang, G. Circular RNA BCRC-3 suppresses bladder cancer proliferation through miR-182-5p/p27 axis. Mol. Cancer, 2018, 17(1), 144.
[http://dx.doi.org/10.1186/s12943-018-0892-z] [PMID: 30285878]
[19]
Zhu, K.P.; Zhang, C.L.; Ma, X.L.; Hu, J.P.; Cai, T.; Zhang, L. Analyzing the interactions of mRNAs and ncRNAs to predict competing endogenous RNA networks in osteosarcoma chemo-resistance. Molecular therapy. J. Am. Soc. Gene Ther., , 2019.
[http://dx.doi.org/10.1016/j.ymthe.2019.01.001]
[20]
Xu, X.; Lu, J.; Wang, F.; Liu, X.; Peng, X.; Yu, B.; Zhao, F.; Li, X. Dynamic changes in plasma microRNAs have potential predictive values in monitoring recurrence and metastasis of nasopharyngeal carcinoma. BioMed Res. Int., 2018., 20187329195
[http://dx.doi.org/10.1155/2018/7329195] [PMID: 29581984]
[21]
Shin, S.S.; Park, S.S.; Hwang, B.; Moon, B.; Kim, W.T.; Kim, W.J.; Moon, S.K. MicroRNA-892b influences proliferation, migration and invasion of bladder cancer cells by mediating the p19ARF/cyclin D1/CDK6 and Sp-1/MMP-9 pathways. Oncol. Rep., 2016, 36(4), 2313-2320.
[http://dx.doi.org/10.3892/or.2016.5052] [PMID: 27573859]
[22]
Jiang, L.; Yu, L.; Zhang, X.; Lei, F.; Wang, L.; Liu, X.; Wu, S.; Zhu, J.; Wu, G.; Cao, L.; Liu, A.; Song, L.; Li, J. miR-892b silencing activates NF-κB and promotes aggressiveness in breast cancer. Cancer Res., 2016, 76(5), 1101-1111.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-1770] [PMID: 26747895]
[23]
Hao, L.; Rong, W.; Bai, L.; Cui, H.; Zhang, S.; Li, Y.; Chen, D.; Meng, X. Upregulated circular RNA circ_0007534 indicates an unfavorable prognosis in pancreatic ductal adenocarcinoma and regulates cell proliferation, apoptosis, and invasion by sponging miR-625 and miR-892b. J. Cell. Biochem., 2019, 120(3), 3780-3789.
[http://dx.doi.org/10.1002/jcb.27658] [PMID: 30382592]
[24]
Perciavalle, R.M.; Opferman, J.T. Delving deeper: MCL-1's contributions to normal and cancer biology. Trends Cell Biol., 2013, 23(1), 22-29.
[http://dx.doi.org/10.1016/j.tcb.2012.08.011] [PMID: 23026029]
[25]
Wertz, I.E.; Kusam, S.; Lam, C.; Okamoto, T.; Sandoval, W.; Anderson, D.J.; Helgason, E.; Ernst, J.A.; Eby, M.; Liu, J.; Belmont, L.D.; Kaminker, J.S.; O’Rourke, K.M.; Pujara, K.; Kohli, P.B.; Johnson, A.R.; Chiu, M.L.; Lill, J.R.; Jackson, P.K.; Fairbrother, W.J.; Seshagiri, S.; Ludlam, M.J.; Leong, K.G.; Dueber, E.C.; Maecker, H.; Huang, D.C.; Dixit, V.M. Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7. Nature, 2011, 471(7336), 110-114.
[http://dx.doi.org/10.1038/nature09779] [PMID: 21368834]
[26]
Ashkenazi, A.; Fairbrother, W.J.; Leverson, J.D.; Souers, A.J. From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors. Nat. Rev. Drug Discov., 2017, 16(4), 273-284.
[http://dx.doi.org/10.1038/nrd.2016.253] [PMID: 28209992]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy