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Protein & Peptide Letters

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

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Research Article

MicroRNA-137 Inhibits Esophageal Squamous Cell Carcinoma by Downregulating DAAM1

Author(s): Weina Li, Xiangdong Bai, Ruyuan Guo, Xiaolong Xing, Huanhu Zhang* and Xuezhen Gao*

Volume 29, Issue 10, 2022

Published on: 06 October, 2022

Page: [882 - 890] Pages: 9

DOI: 10.2174/0929866529666220819123149

Price: $65

Abstract

Background: A growing body of evidence demonstrates that miR-137 acts against cancers; however, the biological function of miR-137 in esophageal squamous cell carcinoma (ESCC) remains to be fully understood.

Objective: The aim of this study is to explore the role of miR-137 in ESCC.

Methods: miR-137 expression was detected by reverse-transcription quantitative polymerase chain reaction (RT-qPCR), and target protein expression was detected by western blot. Cell counting, colony formation and flow cytometry were employed to determine the effects of miR-137 on the growth of ESCC cells. Dual-luciferase reporter assay was performed to validate the binding of miR- 137 with a dishevelled-associated activator of morphogenesis 1 (DAAM1) 3’-UTR.

Results: miR-137 was shown to be down-regulated in ESCC. miR-137 expression was inversely correlated with the 5-year survival rate of ESCC patients. Up-regulated miR-137 attenuated ESCC proliferation and promoted ESCC cell apoptosis. Meanwhile, to further reveal how miR-137 regulated the malignant behaviors of ESCC, the downstream mRNA binding targets of miR-137 were explored. miR-137 was demonstrated to bind DAAM1 3’-UTR and repressed the expression of DAAM1. The expression of DAAM1 and miR-137 in ESCC was inversely correlated. Additionally, the reintroduction of DAAM1 had the capacity to reverse the negative role of miR- 137 in ESCC cell growth.

Conclusion: These findings have uncovered the new function of miR-137 in ESCC via negatively regulating DAAM1, suggesting miR-137 as a potent therapeutic candidate for ESCC treatment.

Keywords: miR-137, ESCC, DAAM1, gene expression, squamous cell carcinoma, downregulating.

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[1]
Enzinger, P.C.; Mayer, R.J. Esophageal cancer. N. Engl. J. Med., 2003, 349(23), 2241-2252.
[http://dx.doi.org/10.1056/NEJMra035010] [PMID: 14657432]
[2]
Kato, H.; Nakajima, M. Treatments for esophageal cancer: A review. Gen. Thorac. Cardiovasc. Surg., 2013, 61(6), 330-335.
[http://dx.doi.org/10.1007/s11748-013-0246-0] [PMID: 23568356]
[3]
Codipilly, D.C.; Qin, Y.; Dawsey, S.M.; Kisiel, J.; Topazian, M.; Ahlquist, D.; Iyer, P.G. Screening for esophageal squamous cell carcinoma: Recent advances. Gastrointest. Endosc., 2018, 88(3), 413-426.
[http://dx.doi.org/10.1016/j.gie.2018.04.2352] [PMID: 29709526]
[4]
Hirano, H.; Kato, K. Systemic treatment of advanced esophageal squamous cell carcinoma: Chemotherapy, molecular-targeting therapy and immunotherapy. Jpn. J. Clin. Oncol., 2019, 49(5), 412-420.
[http://dx.doi.org/10.1093/jjco/hyz034] [PMID: 30920626]
[5]
Bartel, D.P. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell, 2004, 116(2), 281-297.
[http://dx.doi.org/10.1016/S0092-8674(04)00045-5] [PMID: 14744438]
[6]
Ambros, V. The functions of animal microRNAs. Nature, 2004, 431(7006), 350-355.
[http://dx.doi.org/10.1038/nature02871] [PMID: 15372042]
[7]
Garzon, R.; Marcucci, G. Potential of microRNAs for cancer diagnostics, prognostication and therapy. Curr. Opin. Oncol., 2012, 24(6), 655-659.
[http://dx.doi.org/10.1097/CCO.0b013e328358522c] [PMID: 23079782]
[8]
Farazi, T.A.; Spitzer, J.I.; Morozov, P.; Tuschl, T. miRNAs in human cancer. J. Pathol., 2011, 223(2), 102-115.
[http://dx.doi.org/10.1002/path.2806] [PMID: 21125669]
[9]
Rupaimoole, R.; Slack, F.J. MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases. Nat. Rev. Drug Discov., 2017, 16(3), 203-222.
[http://dx.doi.org/10.1038/nrd.2016.246] [PMID: 28209991]
[10]
Kwak, P.B.; Iwasaki, S.; Tomari, Y. The microRNA pathway and cancer. Cancer Sci., 2010, 101(11), 2309-2315.
[http://dx.doi.org/10.1111/j.1349-7006.2010.01683.x] [PMID: 20726859]
[11]
Iorio, M.V.; Croce, C.M. MicroRNA dysregulation in cancer: Diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol. Med., 2017, 9(6), 852.
[http://dx.doi.org/10.15252/emmm.201707779] [PMID: 28572088]
[12]
Momtazi, A.A.; Shahabipour, F.; Khatibi, S.; Johnston, T.P.; Pirro, M.; Sahebkar, A. Curcumin as a MicroRNA regulator in cancer: A review. Rev. Physiol. Biochem. Pharmacol., 2016, 171, 1-38.
[http://dx.doi.org/10.1007/112_2016_3] [PMID: 27457236]
[13]
Chen, B.B.; Chen, X.B.; Bie, L.Y.; Mu, Y.; Wang, H.L.; Lv, H.F.; Li, N.; Ma, Y.J.; Ding, Z.D.; Luo, S.X. Decreased expression of miR-542-3p exerts growth inhibitory functions in esophageal cancer. J. Cancer Res. Ther., 2015, 11(Suppl. 1), C24-C28.
[http://dx.doi.org/10.4103/0973-1482.163834] [PMID: 26323919]
[14]
Zhen, C.; Huang, J.; Lu, J. MicroRNA-652 inhibits the biological characteristics of esophageal squamous cell carcinoma by directly targeting fibroblast growth factor receptor 1. Exp. Ther. Med., 2019, 18(6), 4473-4480.
[http://dx.doi.org/10.3892/etm.2019.8072] [PMID: 31777550]
[15]
Duan, J.; Lu, G.; Li, Y.; Zhou, S.; Zhou, D.; Tao, H. miR-137 functions as a tumor suppressor gene in pituitary adenoma by targeting AKT2. Int. J. Clin. Exp. Pathol., 2019, 12(5), 1557-1564.
[PMID: 31933973]
[16]
Guo, J.; Xia, B.; Meng, F.; Lou, G. miR-137 suppresses cell growth in ovarian cancer by targeting AEG-1. Biochem. Biophys. Res. Commun., 2013, 441(2), 357-363.
[http://dx.doi.org/10.1016/j.bbrc.2013.10.052] [PMID: 24144591]
[17]
Zhang, L.; Li, Z.; Gai, F.; Wang, Y. MicroRNA-137 suppresses tumor growth in epithelial ovarian cancer in vitro and in vivo. Mol. Med. Rep., 2015, 12(2), 3107-3114.
[http://dx.doi.org/10.3892/mmr.2015.3756] [PMID: 25955305]
[18]
Li, X.; Chen, W.; Zeng, W.; Wan, C.; Duan, S.; Jiang, S. microRNA-137 promotes apoptosis in ovarian cancer cells via the regulation of XIAP. Br. J. Cancer, 2017, 116(1), 66-76.
[http://dx.doi.org/10.1038/bjc.2016.379] [PMID: 27875524]
[19]
Chen, W.; Du, J.; Li, X.; Zhi, Z.; Jiang, S. microRNA-137 downregulates MCL1 in ovarian cancer cells and mediates cisplatin-induced apoptosis. Pharmacogenomics, 2020, 21(3), 195-207.
[http://dx.doi.org/10.2217/pgs-2019-0122] [PMID: 31967512]
[20]
Chen, F.; Luo, N.; Hu, Y.; Li, X.; Zhang, K. MiR-137 suppresses triple-negative breast cancer stemness and tumorigenesis by perturbing BCL11A-DNMT1 interaction. Cell. Physiol. Biochem., 2018, 47(5), 2147-2158.
[http://dx.doi.org/10.1159/000491526] [PMID: 29975921]
[21]
Lee, S.J.; Jeong, J.H.; Kang, S.H.; Kang, J.; Kim, E.A.; Lee, J.; Jung, J.H.; Park, H.Y.; Chae, Y.S. MicroRNA-137 inhibits cancer progression by targeting del-1 in triple-negative breast cancer cells. Int. J. Mol. Sci., 2019, 20(24)E6162
[http://dx.doi.org/10.3390/ijms20246162] [PMID: 31817673]
[22]
Ding, F.; Zhang, S.; Gao, S.; Shang, J.; Li, Y.; Cui, N.; Zhao, Q. MiR-137 functions as a tumor suppressor in pancreatic cancer by targeting MRGBP. J. Cell. Biochem., 2018, 119(6), 4799-4807.
[http://dx.doi.org/10.1002/jcb.26676] [PMID: 29331027]
[23]
Xiao, J.; Peng, F.; Yu, C.; Wang, M.; Li, X.; Li, Z.; Jiang, J.; Sun, C. microRNA-137 modulates pancreatic cancer cells tumor growth, invasion and sensitivity to chemotherapy. Int. J. Clin. Exp. Pathol., 2014, 7(11), 7442-7450.
[PMID: 25550779]
[24]
Katoh, M. WNT/PCP signaling pathway and human cancer.(review) Oncol. Rep., 2005, 14(6), 1583-1588.
[http://dx.doi.org/10.3892/or.14.6.1583] [PMID: 16273260]
[25]
Gao, C.; Chen, Y.G. Dishevelled: The hub of Wnt signaling. Cell. Signal., 2010, 22(5), 717-727.
[http://dx.doi.org/10.1016/j.cellsig.2009.11.021] [PMID: 20006983]
[26]
Zhu, Y.; Tian, Y.; Du, J.; Hu, Z.; Yang, L.; Liu, J.; Gu, L. Dvl2-dependent activation of Daam1 and RhoA regulates Wnt5a-induced breast cancer cell migration. PLoS One, 2012, 7(5)e37823
[http://dx.doi.org/10.1371/journal.pone.0037823] [PMID: 22655072]
[27]
Mei, J.; Xu, B.; Hao, L.; Xiao, Z.; Liu, Y.; Yan, T.; Zhu, Y. Overexpressed DAAM1 correlates with metastasis and predicts poor prognosis in breast cancer. Pathol. Res. Pract., 2020, 216(3)152736
[http://dx.doi.org/10.1016/j.prp.2019.152736] [PMID: 31757662]
[28]
Hosseinahli, N.; Aghapour, M.; Duijf, P.H.G.; Baradaran, B. Treating cancer with microRNA replacement therapy: A literature review. J. Cell. Physiol., 2018, 233(8), 5574-5588.
[http://dx.doi.org/10.1002/jcp.26514] [PMID: 29521426]
[29]
Gentilin, E.; Degli Uberti, E.; Zatelli, M.C. Strategies to use microRNAs as therapeutic targets. Best Pract. Res. Clin. Endocrinol. Metab., 2016, 30(5), 629-639.
[http://dx.doi.org/10.1016/j.beem.2016.10.002] [PMID: 27923456]
[30]
Du, F.; Yu, L.; Wu, Y.; Wang, S.; Yao, J.; Zheng, X.; Xie, S.; Zhang, S.; Lu, X.; Liu, Y.; Chen, W. miR-137 alleviates doxorubicin resistance in breast cancer through inhibition of epithelial-mesenchymal transition by targeting DUSP4. Cell Death Dis., 2019, 10(12), 922.
[http://dx.doi.org/10.1038/s41419-019-2164-2] [PMID: 31801953]
[31]
Zhang, W.; Chen, J.H.; Shan, T.; Aguilera-Barrantes, I.; Wang, L.S.; Huang, T.H.; Rader, J.S.; Sheng, X.; Huang, Y.W. miR-137 is a tumor suppressor in endometrial cancer and is repressed by DNA hypermethylation. Lab. Invest., 2018, 98(11), 1397-1407.
[http://dx.doi.org/10.1038/s41374-018-0092-x] [PMID: 29955087]
[32]
Mei, J.; Huang, Y.; Hao, L.; Liu, Y.; Yan, T.; Qiu, T.; Xu, R.; Xu, B.; Xiao, Z.; Jiang, X.; Hu, K.; Zhu, Y. DAAM1-mediated migration and invasion of ovarian cancer cells are suppressed by miR-208a-5p. Pathol. Res. Pract., 2019, 215(7)152452
[http://dx.doi.org/10.1016/j.prp.2019.152452] [PMID: 31104928]
[33]
Xiong, H.; Yan, T.; Zhang, W.; Shi, F.; Jiang, X.; Wang, X.; Li, S.; Chen, Y.; Chen, C.; Zhu, Y. miR-613 inhibits cell migration and invasion by downregulating Daam1 in triple-negative breast cancer. Cell. Signal., 2018, 44, 33-42.
[http://dx.doi.org/10.1016/j.cellsig.2018.01.013] [PMID: 29339084]

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