Login Register Cart 0
Generic placeholder image

Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Hsa_circ_0000437 Inhibits the Development of Endometrial Carcinoma through miR-626/CDKN1B Axis

Author(s): Xiaojuan Li and Yahong Liu*

Volume 29, Issue 7, 2022

Published on: 25 August, 2022

Page: [611 - 620] Pages: 10

DOI: 10.2174/0929866529666220622125016

Price: $65

Abstract

Background: Circular RNAs (circRNAs) are pivotal in cancer biology. Nevertheless, the biological functions of circular RNA hsa_circ_0000437 (circ_0000437) have not yet been elucidated. In the present study, we studied the expression characteristics of circ_0000437 in endometrial carcinoma (EC) and explored the roles and potential mechanisms of circ_0000437 in EC progression.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was adopted to detect the expressions of circ_0000437, microRNA-626 (miR-626) and cyclin-dependent kinase inhibitor 1B (CDKN1B) in EC tissues and cells. 5-Ethynyl-2'-deoxyuridine (EdU), cell counting kit-8 (CCK-8) and Transwell assays were performed to evaluate EC cell proliferation and invasion. The expressions of CDKN1B and epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin and N-cadherin) were detected by Western blot. Moreover, the targeted relationship between miR- 626 and circ_0000437 or CDKN1B was determined by a dual-luciferase reporter and RNA immunoprecipitation (RIP) assays.

Results: Circ_0000437 expression was reduced in EC tissues, and the low expression of circ_0000437 was positively correlated with the lymph node metastasis and high TNM stage of EC patients. Knocking down circ_0000437 promoted the proliferation, invasion and EMT of EC cells. Circ_0000437 directly targeted miR-626 and negatively modulated miR-626 expression in EC cells. CDKN1B was identified as the downstream target of miR-626 in EC cells. Besides, CDKN1B overexpression of miR-626 knockdown reversed the effects of knocking down circ_0000437 on EC cells.

Conclusion: Circ_0000437 regulates the miR-626/CDKN1B pathway to suppress the proliferation, invasion and EMT of EC cells. This indicates that circ_0000437 may be a promising biomarker and therapy target for EC.

Keywords: Circ_0000437, endometrial carcinoma, miR-626, CDKN1B, polymerase chain reaction, circular RNAs (circRNAs).

« Previous Next »
Graphical Abstract

[1]
Urick, M.E.; Bell, D.W. Clinical actionability of molecular targets in endometrial cancer. Nat. Rev. Cancer, 2019, 19(9), 510-521.
[http://dx.doi.org/10.1038/s41568-019-0177-x] [PMID: 31388127]
[2]
Amant, F.; Moerman, P.; Neven, P.; Timmerman, D.; Van Limbergen, E.; Vergote, I. Endometrial cancer. Lancet, 2005, 366(9484), 491-505.
[http://dx.doi.org/10.1016/S0140-6736(05)67063-8] [PMID: 16084259]
[3]
Neri, M.; Peiretti, M.; Melis, G.B.; Piras, B.; Vallerino, V.; Paoletti, A.M.; Madeddu, C.; Scartozzi, M.; Mais, V. Systemic therapy for the treatment of endometrial cancer. Expert Opin. Pharmacother., 2019, 20(16), 2019-2032.
[http://dx.doi.org/10.1080/14656566.2019.1654996] [PMID: 31451034]
[4]
Pecorelli, S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int. J. Gynaecol. Obstet., 2009, 105(2), 103-104.
[http://dx.doi.org/10.1016/j.ijgo.2009.02.012] [PMID: 19367689]
[5]
Wang, Y.; Yin, L.; Sun, X. CircRNA hsa_circ_0002577 accelerates endometrial cancer progression through activating IGF1R/PI3K/Akt pathway. J. Exp. Clin. Cancer Res., 2020, 39(1), 169-169.
[http://dx.doi.org/10.1186/s13046-020-01679-8] [PMID: 32847606]
[6]
Li, R.; Jiang, J.; Shi, H.; Qian, H.; Zhang, X.; Xu, W. CircRNA: a rising star in gastric cancer. Cell. Mol. Life Sci., 2020, 77(9), 1661-1680.
[http://dx.doi.org/10.1007/s00018-019-03345-5] [PMID: 31659415]
[7]
Wu, N.; Jin, L.; Cai, J. Profiling and bioinformatics analyses reveal differential circular RNA expression in hypertensive patients. Clin. Exp. Hypertens., 2017, 39(5), 454-459.
[8]
Chen, L.L.; Yang, L. Regulation of circRNA biogenesis. RNA Biol., 2015, 12(4), 381-388.
[http://dx.doi.org/10.1080/15476286.2015.1020271] [PMID: 25746834]
[9]
Suzuki, H.; Zuo, Y.; Wang, J.; Zhang, M.Q.; Malhotra, A.; Mayeda, A. Characterization of RNase R-digested cellular RNA source that consists of lariat and circular RNAs from pre-mRNA splicing. Nucleic Acids Res., 2006, 34(8), e63.
[http://dx.doi.org/10.1093/nar/gkl151] [PMID: 16682442]
[10]
Patop, I.L.; Wüst, S.; Kadener, S. Past, present, and future of circRNAs. EMBO J., 2019, 38(16), e100836.
[http://dx.doi.org/10.15252/embj.2018100836] [PMID: 31343080]
[11]
Zong, Z.H.; Liu, Y.; Chen, S.; Zhao, Y. Circ_PUM1 promotes the development of endometrial cancer by targeting the miR-136/NOTCH3 pathway. J. Cell. Mol. Med., 2020, 24(7), 4127-4135.
[http://dx.doi.org/10.1111/jcmm.15069] [PMID: 32073729]
[12]
Liu, Y.; Chen, S.; Zong, Z.H.; Guan, X.; Zhao, Y. CircRNA WHSC1 targets the miR-646/NPM1 pathway to promote the development of endometrial cancer. J. Cell. Mol. Med., 2020, 24(12), 6898-6907.
[http://dx.doi.org/10.1111/jcmm.15346] [PMID: 32378344]
[13]
Jia, Y.; Liu, M.; Wang, S. CircRNA hsa_circRNA_0001776 inhibits proliferation and promotes apoptosis in endometrial cancer via downregulating LRIG2 by sponging miR-182. Cancer Cell Int., 2020, 20(1), 412.
[http://dx.doi.org/10.1186/s12935-020-01437-y] [PMID: 32863771]
[14]
Ye, F.; Tang, Q.L.; Ma, F.; Cai, L.; Chen, M.; Ran, X.X.; Wang, X.Y.; Jiang, X.F. Analysis of the circular RNA transcriptome in the grade 3 endometrial cancer. Cancer Manag. Res., 2019, 11, 6215-6227.
[http://dx.doi.org/10.2147/CMAR.S197343] [PMID: 31308756]
[15]
Saliminejad, K.; Khorram Khorshid, H.R.; Soleymani Fard, S.; Ghaffari, S.H. An overview of microRNAs: Biology, functions, therapeutics, and analysis methods. J. Cell. Physiol., 2019, 234(5), 5451-5465.
[http://dx.doi.org/10.1002/jcp.27486] [PMID: 30471116]
[16]
Lee, Y.S.; Dutta, A. MicroRNAs in cancer. Annu. Rev. Pathol., 2009, 4(1), 199-227.
[http://dx.doi.org/10.1146/annurev.pathol.4.110807.092222] [PMID: 18817506]
[17]
Bertoli, G.; Cava, C.; Castiglioni, I. MicroRNAs: New biomarkers for diagnosis, prognosis, therapy prediction and therapeutic tools for breast cancer. Theranostics, 2015, 5(10), 1122-1143.
[http://dx.doi.org/10.7150/thno.11543] [PMID: 26199650]
[18]
Zhang, H.C.; Han, Y.Y.; Zhang, X.M.; Xiao, N.; Jiang, T.; Zhu, S.; Wang, E.P.; Chen, C.B. miR-522 facilitates the prosperities of endometrial carcinoma cells by directly binding to monoamine oxidase B. Kaohsiung J. Med. Sci., 2019, 35(10), 598-606.
[http://dx.doi.org/10.1002/kjm2.12107] [PMID: 31271496]
[19]
Zhuang, L.; Qu, H.; Cong, J.; Dai, H.; Liu, X. miR-181c affects estrogen-dependent endometrial carcinoma cell growth by targeting PTEN. Endocr. J., 2019, 66(6), 523-533.
[http://dx.doi.org/10.1507/endocrj.EJ18-0538] [PMID: 30971627]
[20]
Dong, W.; Bi, J.; Liu, H.; Yan, D.; He, Q.; Zhou, Q.; Wang, Q.; Xie, R.; Su, Y.; Yang, M.; Lin, T.; Huang, J. Circular RNA ACVR2A suppresses bladder cancer cells proliferation and metastasis through miR-626/EYA4 axis. Mol. Cancer, 2019, 18(1), 95.
[http://dx.doi.org/10.1186/s12943-019-1025-z] [PMID: 31101108]
[21]
Kristensen, L.S.; Hansen, T.B.; Venø, M.T.; Kjems, J. Circular RNAs in cancer: Opportunities and challenges in the field. Oncogene, 2018, 37(5), 555-565.
[http://dx.doi.org/10.1038/onc.2017.361] [PMID: 28991235]
[22]
Chen, B.; Huang, S. Circular RNA: An emerging non-coding RNA as a regulator and biomarker in cancer. Cancer Lett., 2018, 418, 41-50.
[http://dx.doi.org/10.1016/j.canlet.2018.01.011] [PMID: 29330104]
[23]
Liu, Y.; Chang, Y.; Cai, Y. Hsa_circ_0061140 promotes endometrial carcinoma progression via regulating miR-149-5p/STAT3. Gene, 2020, 745, 144625.
[http://dx.doi.org/10.1016/j.gene.2020.144625] [PMID: 32224273]
[24]
Wei, D.; Tian, M.; Fan, W.; Zhong, X.; Wang, S.; Chen, Y.; Zhang, S. Circular RNA circ_0000043 promotes endometrial carcinoma progression by regulating miR-1271-5p/CTNND1 axis. Arch. Gynecol. Obstet., 2021, 303(4), 1075-1087.
[http://dx.doi.org/10.1007/s00404-020-05849-z] [PMID: 33128584]
[25]
Lu, T.X.; Rothenberg, M.E. MicroRNA. J. Allergy Clin. Immunol., 2018, 141(4), 1202-1207.
[http://dx.doi.org/10.1016/j.jaci.2017.08.034] [PMID: 29074454]
[26]
Wu, M.; Wang, G.; Tian, W.; Deng, Y.; Xu, Y. miRNA-based therapeutics for lung cancer. Curr. Pharm. Des., 2018, 23(39), 5989-5996.
[http://dx.doi.org/10.2174/1381612823666170714151715] [PMID: 28714413]
[27]
Jiang, T.; Sui, D.; You, D.; Yao, S.; Zhang, L.; Wang, Y.; Zhao, J.; Zhang, Y. miR-29a-5p inhibits proliferation and invasion and induces apoptosis in endometrial carcinoma via targeting TPX2. Cell Cycle, 2018, 17(10), 1268-1278.
[http://dx.doi.org/10.1080/15384101.2018.1475829] [PMID: 29888640]
[28]
Bao, W.; Wang, H.H.; Tian, F.J.; He, X.Y.; Qiu, M.T.; Wang, J.Y.; Zhang, H.J.; Wang, L.H.; Wan, X.P. A TrkB-STAT3-miR-204-5p regulatory circuitry controls proliferation and invasion of endometrial carcinoma cells. Mol. Cancer, 2013, 12(1), 155.
[http://dx.doi.org/10.1186/1476-4598-12-155] [PMID: 24321270]
[29]
Liu, Q.; Cao, G.; Wan, Y.; Xu, C.; He, Y.; Li, G. Hsa_circ_0001073 targets miR-626/LIFR axis to inhibit lung cancer progression. Environ. Toxicol., 2021, 36(6), 1052-1060.
[http://dx.doi.org/10.1002/tox.23104] [PMID: 33475233]
[30]
Shen, Q.; He, T.; Yuan, H. Hsa_circ_0002577 promotes endometrial carcinoma progression via regulating miR-197/CTNND1 axis and activating Wnt/β-catenin pathway. Cell Cycle, 2019, 18(11), 1229-1240.
[http://dx.doi.org/10.1080/15384101.2019.1617004] [PMID: 31081718]
[31]
Wu, B.; Ren, A.; Tian, Y.; Huang, R. Hsa_circ_0075960 serves as a sponge for miR-361-3p/SH2B1 in endometrial carcinoma. Technol. Cancer Res. Treat., 2020, 19, 1533033820983079.
[http://dx.doi.org/10.1177/1533033820983079] [PMID: 33356989]
[32]
Qin, X.; Guo, H.; Wang, X.; Zhu, X.; Yan, M.; Wang, X.; Xu, Q.; Shi, J.; Lu, E.; Chen, W.; Zhang, J. Exosomal miR-196a derived from cancer-associated fibroblasts confers cisplatin resistance in head and neck cancer through targeting CDKN1B and ING5. Genome Biol., 2019, 20(1), 12-12.
[http://dx.doi.org/10.1186/s13059-018-1604-0] [PMID: 30642385]
[33]
Abukhdeir, A.M.; Park, B.H. P21 and p27: Roles in carcinogenesis and drug resistance. Expert Rev. Mol. Med., 2008, 10, e19-e19.
[http://dx.doi.org/10.1017/S1462399408000744] [PMID: 18590585]
[34]
Bochis, O.V.; Irimie, A.; Pichler, M.; Berindan-Neagoe, I. The role of Skp2 and its substrate CDKN1B (p27) in colorectal cancer. J. Gastrointestin. Liver Dis., 2015, 24(2), 225-234.
[http://dx.doi.org/10.15403/jgld.2014.1121.242.skp2] [PMID: 26114183]
[35]
Lynch, S.M.; McKenna, M.M.; Walsh, C.P.; McKenna, D.J. miR-24 regulates CDKN1B/p27 expression in prostate cancer. Prostate, 2016, 76(7), 637-648.
[http://dx.doi.org/10.1002/pros.23156] [PMID: 26847530]
[36]
Bamberger, A.M.; Riethdorf, L.; Milde-Langosch, K. Strongly reduced expression of the cell cycle inhibitor p27 in endometrial neoplasia. Virchows Arch., 1999, 434(5), 423-428.

Rights & Permissions Print Cite
Article Metrics
27
2
© 2024 Bentham Science Publishers | Privacy Policy