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Published in: Cancer Cell International 1/2020

Open Access 01-12-2020 | Ovarian Cancer | Primary research

Circ_0015756 promotes the progression of ovarian cancer by regulating miR-942-5p/CUL4B pathway

Authors: Zhenhua Du, Lei Wang, Yu Xia

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

Ovarian cancer (OC) is the gynecologic cancer with the highest mortality. Circular RNAs (circRNAs) play a vital role in the development and progression of cancer. This study aimed to explore the potential role of circ_0015756 in OC and its molecular mechanism.

Methods

The levels of circ_0015756, microRNA-942-5p (miR-942-5p) and Cullin 4B (CUL4B) were determined by quantitative real-time PCR (qRT-PCR) or Western blot assay. Cell proliferation, apoptosis, migration and invasion were assessed by Cell Counting Kit-8 (CCK-8), colony formation assay, flow cytometry and transwell assay. The levels of proliferation-related and metastasis-related proteins were measured by Western blot assay. The relationship between miR-942-5p and circ_0015756 or CUL4B was verified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Xenograft assay was used to analyze tumor growth in vivo.

Results

Circ_0015756 and CUL4B levels were increased, while miR-942-5p level was decreased in OC tissues and cells. Depletion of circ_0015756 suppressed proliferation, migration and invasion and promoted apoptosis in OC cells. Down-regulation of circ_0015756 hindered OC cell progression via modulating miR-942-5p. Also, up-regulation of miR-942-5p impeded OC cell development by targeting CUL4B. Mechanistically, circ_0015756 up-regulated CUL4B via sponging miR-942-5p. Moreover, circ_0015756 silencing inhibited tumor growth in vivo.

Conclusion

Knockdown of circ_0015756 suppressed OC progression via regulating miR-942-5p/CUL4B axis, suggesting that circ_0015756 might be a potential therapeutic target for ovarian cancer.
Literature
1.
go back to reference Jayson GC, Kohn EC, Kitchener HC, Ledermann JA. Ovarian cancer. Lancet. 2014;384(9951):1376–88.CrossRef Jayson GC, Kohn EC, Kitchener HC, Ledermann JA. Ovarian cancer. Lancet. 2014;384(9951):1376–88.CrossRef
2.
go back to reference Matulonis UA, Sood AK, Fallowfield L, Howitt BE, Sehouli J, Karlan BY. Ovarian cancer. Nat Rev Dis Primers. 2016;2:16061.CrossRef Matulonis UA, Sood AK, Fallowfield L, Howitt BE, Sehouli J, Karlan BY. Ovarian cancer. Nat Rev Dis Primers. 2016;2:16061.CrossRef
3.
go back to reference Tew WP, Muss HB, Kimmick GG, Von Gruenigen VE, Lichtman SM. Breast and ovarian cancer in the older woman. J Clin Oncol. 2014;32(24):2553–61.CrossRef Tew WP, Muss HB, Kimmick GG, Von Gruenigen VE, Lichtman SM. Breast and ovarian cancer in the older woman. J Clin Oncol. 2014;32(24):2553–61.CrossRef
4.
go back to reference Longuespee R, Boyon C, Desmons A, Vinatier D, Leblanc E, Farre I, Wisztorski M, Ly K, D’Anjou F, Day R, et al. Ovarian cancer molecular pathology. Cancer Metastasis Rev. 2012;31(3–4):713–32.CrossRef Longuespee R, Boyon C, Desmons A, Vinatier D, Leblanc E, Farre I, Wisztorski M, Ly K, D’Anjou F, Day R, et al. Ovarian cancer molecular pathology. Cancer Metastasis Rev. 2012;31(3–4):713–32.CrossRef
5.
go back to reference Qian L, Yu S, Chen Z, Meng Z, Huang S, Wang P. The emerging role of circRNAs and their clinical significance in human cancers. Biochim Biophys Acta Rev Cancer. 2018;1870(2):247–60.CrossRef Qian L, Yu S, Chen Z, Meng Z, Huang S, Wang P. The emerging role of circRNAs and their clinical significance in human cancers. Biochim Biophys Acta Rev Cancer. 2018;1870(2):247–60.CrossRef
6.
go back to reference He J, Xie Q, Xu H, Li J, Li Y. Circular RNAs and cancer. Cancer Lett. 2017;396:138–44.CrossRef He J, Xie Q, Xu H, Li J, Li Y. Circular RNAs and cancer. Cancer Lett. 2017;396:138–44.CrossRef
7.
go back to reference Dong P, Xu D, Xiong Y, Yue J, Ihira K, Konno Y, Watari H. The expression, functions and mechanisms of circular RNAs in gynecological cancers. Cancers (Basel). 2020;12(6):1472.CrossRef Dong P, Xu D, Xiong Y, Yue J, Ihira K, Konno Y, Watari H. The expression, functions and mechanisms of circular RNAs in gynecological cancers. Cancers (Basel). 2020;12(6):1472.CrossRef
9.
go back to reference Li Y, Lin S, An N. Hsa_circ_0009910: oncogenic circular RNA targets microRNA-145 in ovarian cancer cells. Cell Cycle. 2020;19(15):1857–68.CrossRef Li Y, Lin S, An N. Hsa_circ_0009910: oncogenic circular RNA targets microRNA-145 in ovarian cancer cells. Cell Cycle. 2020;19(15):1857–68.CrossRef
10.
go back to reference Wang G, Zhang H, Li P. Upregulation of hsa_circRNA_102958 indicates poor prognosis and promotes ovarian cancer progression through miR-1205/SH2D3A axis. Cancer Manag Res. 2020;12:4045–53.CrossRef Wang G, Zhang H, Li P. Upregulation of hsa_circRNA_102958 indicates poor prognosis and promotes ovarian cancer progression through miR-1205/SH2D3A axis. Cancer Manag Res. 2020;12:4045–53.CrossRef
11.
go back to reference Zhang M, Xia B, Xu Y, Zhang Y, Xu J, Lou G. Circular RNA (hsa_circ_0051240) promotes cell proliferation, migration and invasion in ovarian cancer through miR-637/KLK4 axis. Artif Cells Nanomed Biotechnol. 2019;47(1):1224–33.CrossRef Zhang M, Xia B, Xu Y, Zhang Y, Xu J, Lou G. Circular RNA (hsa_circ_0051240) promotes cell proliferation, migration and invasion in ovarian cancer through miR-637/KLK4 axis. Artif Cells Nanomed Biotechnol. 2019;47(1):1224–33.CrossRef
12.
go back to reference Chipman LB, Pasquinelli AE. miRNA targeting: growing beyond the Seed. Trends Genet. 2019;35(3):215–22.CrossRef Chipman LB, Pasquinelli AE. miRNA targeting: growing beyond the Seed. Trends Genet. 2019;35(3):215–22.CrossRef
13.
go back to reference Wang F, Niu G, Chen X, Cao F. Molecular imaging of microRNAs. Eur J Nucl Med Mol Imaging. 2011;38(8):1572–9.CrossRef Wang F, Niu G, Chen X, Cao F. Molecular imaging of microRNAs. Eur J Nucl Med Mol Imaging. 2011;38(8):1572–9.CrossRef
14.
go back to reference Yang S, Zhang X, Sun Y, Shi J, Jiang D, Wang J, Liu Y, Hu C, Pan J, Zheng L, et al. MicroRNA-362-3p inhibits migration and invasion via targeting BCAP31 in cervical cancer. Front Mol Biosci. 2020;7:107.CrossRef Yang S, Zhang X, Sun Y, Shi J, Jiang D, Wang J, Liu Y, Hu C, Pan J, Zheng L, et al. MicroRNA-362-3p inhibits migration and invasion via targeting BCAP31 in cervical cancer. Front Mol Biosci. 2020;7:107.CrossRef
15.
go back to reference Zheng X, Xu K, Zhu L, Mao M, Zhang F, Cui L. MiR-486-5p act as a biomarker in endometrial carcinoma: promotes cell proliferation, migration, invasion by targeting MARK1. Onco Targets Ther. 2020;13:4843–53.CrossRef Zheng X, Xu K, Zhu L, Mao M, Zhang F, Cui L. MiR-486-5p act as a biomarker in endometrial carcinoma: promotes cell proliferation, migration, invasion by targeting MARK1. Onco Targets Ther. 2020;13:4843–53.CrossRef
16.
go back to reference Xie J, Wang S, Li G, Zhao X, Jiang F, Liu J, Tan W. circEPSTI1 regulates ovarian cancer progression via decoying miR-942. J Cell Mol Med. 2019;23(5):3597–602.CrossRef Xie J, Wang S, Li G, Zhao X, Jiang F, Liu J, Tan W. circEPSTI1 regulates ovarian cancer progression via decoying miR-942. J Cell Mol Med. 2019;23(5):3597–602.CrossRef
17.
go back to reference Trinidad CV, Tetlow AL, Bantis LE, Godwin AK. Reducing ovarian cancer mortality through early detection: approaches using circulating biomarkers. Cancer Prev Res (Phila). 2020;13(3):241–52.CrossRef Trinidad CV, Tetlow AL, Bantis LE, Godwin AK. Reducing ovarian cancer mortality through early detection: approaches using circulating biomarkers. Cancer Prev Res (Phila). 2020;13(3):241–52.CrossRef
18.
go back to reference Yang X, Mei J, Wang H, Gu D, Ding J, Liu C. The emerging roles of circular RNAs in ovarian cancer. Cancer Cell Int. 2020;20:265.CrossRef Yang X, Mei J, Wang H, Gu D, Ding J, Liu C. The emerging roles of circular RNAs in ovarian cancer. Cancer Cell Int. 2020;20:265.CrossRef
19.
go back to reference Feng Y, Wang Q, Shi C, Liu C, Zhang Z. Does circular RNA exert significant effects in ovarian cancer? Crit Rev Eukaryot Gene Expr. 2019;29(2):161–70.CrossRef Feng Y, Wang Q, Shi C, Liu C, Zhang Z. Does circular RNA exert significant effects in ovarian cancer? Crit Rev Eukaryot Gene Expr. 2019;29(2):161–70.CrossRef
20.
go back to reference Tang Q, Hann SS. Biological roles and mechanisms of circular RNA in human cancers. Onco Targets Ther. 2020;13:2067–92.CrossRef Tang Q, Hann SS. Biological roles and mechanisms of circular RNA in human cancers. Onco Targets Ther. 2020;13:2067–92.CrossRef
21.
go back to reference Dori M, Bicciato S. Integration of bioinformatic predictions and experimental data to identify circRNA-miRNA associations. Genes (Basel). 2019;10(9):642.CrossRef Dori M, Bicciato S. Integration of bioinformatic predictions and experimental data to identify circRNA-miRNA associations. Genes (Basel). 2019;10(9):642.CrossRef
22.
go back to reference Ou R, Mo L, Tang H, Leng S, Zhu H, Zhao L, Ren Y, Xu Y. circRNA-AKT1 sequesters miR-942-5p to upregulate AKT1 and promote cervical cancer progression. Mol Ther Nucleic Acids. 2020;20:308–22.CrossRef Ou R, Mo L, Tang H, Leng S, Zhu H, Zhao L, Ren Y, Xu Y. circRNA-AKT1 sequesters miR-942-5p to upregulate AKT1 and promote cervical cancer progression. Mol Ther Nucleic Acids. 2020;20:308–22.CrossRef
23.
go back to reference Lu J, Wang YH, Huang XY, Xie JW, Wang JB, Lin JX, Chen QY, Cao LL, Huang CM, Zheng CH, et al. circ-CEP85L suppresses the proliferation and invasion of gastric cancer by regulating NFKBIA expression via miR-942-5p. J Cell Physiol. 2020;235(9):6287–99.CrossRef Lu J, Wang YH, Huang XY, Xie JW, Wang JB, Lin JX, Chen QY, Cao LL, Huang CM, Zheng CH, et al. circ-CEP85L suppresses the proliferation and invasion of gastric cancer by regulating NFKBIA expression via miR-942-5p. J Cell Physiol. 2020;235(9):6287–99.CrossRef
24.
go back to reference Zhang S, Lu Z, Unruh AK, Ivan C, Baggerly KA, Calin GA, Li Z, Bast RC Jr, Le XF. Clinically relevant microRNAs in ovarian cancer. Mol Cancer Res. 2015;13(3):393–401.CrossRef Zhang S, Lu Z, Unruh AK, Ivan C, Baggerly KA, Calin GA, Li Z, Bast RC Jr, Le XF. Clinically relevant microRNAs in ovarian cancer. Mol Cancer Res. 2015;13(3):393–401.CrossRef
26.
go back to reference Luo N, Gao HM, Wang YQ, Li HJ, Li Y. MiR-942-5p alleviates septic acute kidney injury by targeting FOXO3. Eur Rev Med Pharmacol Sci. 2020;24(11):6237–44.PubMed Luo N, Gao HM, Wang YQ, Li HJ, Li Y. MiR-942-5p alleviates septic acute kidney injury by targeting FOXO3. Eur Rev Med Pharmacol Sci. 2020;24(11):6237–44.PubMed
27.
go back to reference Hannah J, Zhou P. Distinct and overlapping functions of the cullin E3 ligase scaffolding proteins CUL4A and CUL4B. Gene. 2015;573(1):33–45.CrossRef Hannah J, Zhou P. Distinct and overlapping functions of the cullin E3 ligase scaffolding proteins CUL4A and CUL4B. Gene. 2015;573(1):33–45.CrossRef
28.
go back to reference Li Y, Wang X. The role of cullin4B in human cancers. Exp Hematol Oncol. 2017;6:17.CrossRef Li Y, Wang X. The role of cullin4B in human cancers. Exp Hematol Oncol. 2017;6:17.CrossRef
29.
go back to reference Liu X, Cui J, Gong L, Tian F, Shen Y, Chen L, Wang Y, Xia Y, Liu L, Ye X, et al. The CUL4B-miR-372/373-PIK3CA-AKT axis regulates metastasis in bladder cancer. Oncogene. 2020;39(17):3588–603.CrossRef Liu X, Cui J, Gong L, Tian F, Shen Y, Chen L, Wang Y, Xia Y, Liu L, Ye X, et al. The CUL4B-miR-372/373-PIK3CA-AKT axis regulates metastasis in bladder cancer. Oncogene. 2020;39(17):3588–603.CrossRef
30.
go back to reference Li Y, Hu H, Wang Y, Fan Y, Yang Y, Guo B, Xie X, Lian J, Jiang B, Han B, et al. CUL4B contributes to cancer stemness by repressing tumor suppressor miR34a in colorectal cancer. Oncogenesis. 2020;9(2):20.CrossRef Li Y, Hu H, Wang Y, Fan Y, Yang Y, Guo B, Xie X, Lian J, Jiang B, Han B, et al. CUL4B contributes to cancer stemness by repressing tumor suppressor miR34a in colorectal cancer. Oncogenesis. 2020;9(2):20.CrossRef
31.
go back to reference Zhang H, Wang A, Tan Y, Wang S, Ma Q, Chen X, He Z. NCBP1 promotes the development of lung adenocarcinoma through up-regulation of CUL4B. J Cell Mol Med. 2019;23(10):6965–77.CrossRef Zhang H, Wang A, Tan Y, Wang S, Ma Q, Chen X, He Z. NCBP1 promotes the development of lung adenocarcinoma through up-regulation of CUL4B. J Cell Mol Med. 2019;23(10):6965–77.CrossRef
32.
go back to reference Duan PJ, Zhao JH, Xie LL. Cul4B promotes the progression of ovarian cancer by upregulating the expression of CDK2 and CyclinD1. J Ovarian Res. 2020;13(1):76.CrossRef Duan PJ, Zhao JH, Xie LL. Cul4B promotes the progression of ovarian cancer by upregulating the expression of CDK2 and CyclinD1. J Ovarian Res. 2020;13(1):76.CrossRef
33.
go back to reference Eisa AA, De S, Detwiler A, Gilker E, Ignatious AC, Vijayaraghavan S, Kline D. YWHA (14-3-3) protein isoforms and their interactions with CDC25B phosphatase in mouse oogenesis and oocyte maturation. BMC Dev Biol. 2019;19(1):20.CrossRef Eisa AA, De S, Detwiler A, Gilker E, Ignatious AC, Vijayaraghavan S, Kline D. YWHA (14-3-3) protein isoforms and their interactions with CDC25B phosphatase in mouse oogenesis and oocyte maturation. BMC Dev Biol. 2019;19(1):20.CrossRef
34.
go back to reference De S, Marcinkiewicz JL, Vijayaraghavan S, Kline D. Expression of 14-3-3 protein isoforms in mouse oocytes, eggs and ovarian follicular development. BMC Res Notes. 2012;5:57.CrossRef De S, Marcinkiewicz JL, Vijayaraghavan S, Kline D. Expression of 14-3-3 protein isoforms in mouse oocytes, eggs and ovarian follicular development. BMC Res Notes. 2012;5:57.CrossRef
35.
go back to reference De S, Kline D. Evidence for the requirement of 14-3-3eta (YWHAH) in meiotic spindle assembly during mouse oocyte maturation. BMC Dev Biol. 2013;13:10.CrossRef De S, Kline D. Evidence for the requirement of 14-3-3eta (YWHAH) in meiotic spindle assembly during mouse oocyte maturation. BMC Dev Biol. 2013;13:10.CrossRef
Metadata
Title
Circ_0015756 promotes the progression of ovarian cancer by regulating miR-942-5p/CUL4B pathway
Authors
Zhenhua Du
Lei Wang
Yu Xia
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01666-1

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