Upregulation of miR‑33b promotes endometriosis via inhibition of Wnt/β‑catenin signaling and ZEB1 expression

Zhang,Haiyan; Li,Guang; Sheng,Xiugui; Zhang,Shiqian

doi:10.3892/mmr.2019.9870

Upregulation of miR‑33b promotes endometriosis via inhibition of Wnt/β‑catenin signaling and ZEB1 expression

Authors:
- Haiyan Zhang
- Guang Li
- Xiugui Sheng
- Shiqian Zhang
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Affiliations: Department of Gynecology, Affiliated Qilu Hospital of Shandong University, Jinan, Shandong 250002, P.R. China, Department of Gynecology Ward 1, Linyi City People's Hospital, Linyi, Shandong 276000, P.R. China, Department of Gynecology, Chinese Academy of Medical Sciences Tumor Hospital, Beijing 100021, P.R. China
Published online on: January 17, 2019 https://doi.org/10.3892/mmr.2019.9870
Pages: 2144-2152
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the role and mechanisms of microRNA (miR)‑33b in endometriosis (Ems). Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), MTT assays, flow cytometry, caspase‑3/9 activity assays and western blotting were performed in the present study. Initially, miR‑33b expression in an Ems rat model was investigated by RT‑qPCR and was demonstrated to be upregulated in Ems tissue samples of rats compared with the control group. In addition, miR‑33b upregulation inhibited cell growth and enhanced apoptosis in an Ems model (primary cell cultures) compared with the control group. In addition, miR‑33b up‑regulation reduced Wnt/β‑catenin signaling pathway and suppressed zinc finger E‑box‑binding homeobox 1 (ZEB1) protein expression in the in vitro Ems model (primary cell cultures) compared with the control group. Furthermore, small interfering‑ZEB1 ameliorated the effects of miR‑33b downregulation on Ems cell growth in the in vitro Ems model. Additionally, a Wnt agonist reduced the effects of miR‑33b upregulation on Ems cell growth in the in vitro Ems model. In conclusion, the present study demonstrated that upregulation of miR‑33b may promote Ems through Wnt/β‑catenin by ZEB1 expression.

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1	Kang JL, Wang XX, Nie ML and Huang XH: Efficacy of gonadotropin-releasing hormone agonist and an extended-interval dosing regimen in the treatment of patients with adenomyosis and endometriosis. Gynecol Obstet Invest. 69:73–77. 2010. View Article : Google Scholar : PubMed/NCBI
2	Soto E, Luu TH, Liu X, Magrina JF, Wasson MN, Einarsson JI, Cohen SL and Falcone T: Laparoscopy vs. Robotic Surgery for Endometriosis (LAROSE): A multicenter, randomized, controlled trial. Fertil Steril. 107:996–1002 e1003. 2017. View Article : Google Scholar : PubMed/NCBI
3	Nematian SE, Mamillapalli R, Kadakia TS, Majidi Zolbin M, Moustafa S and Taylor HS: Systemic inflammation induced by microRNAs: Endometriosis derived alterations in circulating microRNA 125b-5p and let7b-5p regulate macrophage cytokine production. J Clin Endocrinol Metab. 103:64–74. 2018. View Article : Google Scholar : PubMed/NCBI
4	Shen L, Yang S, Huang W, Xu W, Wang Q, Song Y and Liu Y: MicroRNA23a and microRNA23b deregulation derepresses SF-1 and upregulates estrogen signaling in ovarian endometriosis. J Clin Endocrinol Metab. 98:1575–1582. 2013. View Article : Google Scholar : PubMed/NCBI
5	Wright KR, Mitchell B and Santanam N: Redox regulation of microRNAs in endometriosis-associated pain. Redox Biol. 12:956–966. 2017. View Article : Google Scholar : PubMed/NCBI
6	Zhang L, Xiong W, Xiong Y, Liu H, Li N, Du Y and Liu Y: Intracellular wnt/beta-catenin signaling underlying 17beta-estradiol-induced matrix metalloproteinase 9 expression in human endometriosis. Biol Reprod. 94:702016. View Article : Google Scholar : PubMed/NCBI
7	Pazhohan A, Amidi F, Akbari-Asbagh F, Seyedrezazadeh E, Farzadi L, Khodarahmin M, Mehdinejadiani S and Sobhani A: The Wnt/β-catenin signaling in endometriosis, the expression of total and active forms of β-catenin, total and inactive forms of glycogen synthase kinase-3β, WNT7a and DICKKOPF-1. Eur J Obstet Gynecol Reprod Biol. 220:1–5. 2017. View Article : Google Scholar : PubMed/NCBI
8	Zhang P, Sun Y and Ma L: ZEB1: At the crossroads of epithelial-mesenchymal transition, metastasis and therapy resistance. Cell Cycle. 14:481–487. 2015. View Article : Google Scholar : PubMed/NCBI
9	Schmalhofer O, Brabletz S and Brabletz T: E-cadherin, beta-catenin, and ZEB1 in malignant progression of cancer. Cancer Metastasis Rev. 28:151–166. 2009. View Article : Google Scholar : PubMed/NCBI
10	Browne G, Sayan AE and Tulchinsky E: ZEB proteins link cell motility with cell cycle control and cell survival in cancer. Cell Cycle. 9:886–891. 2010. View Article : Google Scholar : PubMed/NCBI
11	Eggers JC, Martino V, Reinbold R, Schäfer SD, Kiesel L, Starzinski-Powitz A, Schüring AN, Kemper B, Greve B and Götte M: microRNA miR-200b affects proliferation, invasiveness and stemness of endometriotic cells by targeting ZEB1, ZEB2 and KLF4. Reprod Biomed Online. 32:434–445. 2016. View Article : Google Scholar : PubMed/NCBI
12	Wang ZH, Zhang JL, Duan YL, Zhang QS, Li GF and Zheng DL: MicroRNA-214 participates in the neuroprotective effect of resveratrol via inhibiting α-synuclein expression in MPTP-induced Parkinson's disease mouse. Biomed Pharmacother. 74:252–256. 2015. View Article : Google Scholar : PubMed/NCBI
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
14	Maegdefessel L, Spin JM, Raaz U, Eken SM, Toh R, Azuma J, Adam M, Nakagami F, Heymann HM, Chernogubova E, et al: miR-24 limits aortic vascular inflammation and murine abdominal aneurysm development. Nat Commun. 5:52142014. View Article : Google Scholar : PubMed/NCBI
15	Nothnick WB: MicroRNAs and endometriosis: Distinguishing drivers from passengers in disease pathogenesis. Semin Reprod Med. 35:173–180. 2017. View Article : Google Scholar : PubMed/NCBI
16	Matsuzaki S and Darcha C: Involvement of the Wnt/β-catenin signaling pathway in the cellular and molecular mechanisms of fibrosis in endometriosis. PLoS One. 8:e768082013. View Article : Google Scholar : PubMed/NCBI
17	Tanwar PS, Lee HJ, Zhang L, Zukerberg LR, Taketo MM, Rueda BR and Teixeira JM: Constitutive activation of Beta-catenin in uterine stroma and smooth muscle leads to the development of mesenchymal tumors in mice. Biol Reprod. 81:545–552. 2009. View Article : Google Scholar : PubMed/NCBI
18	Zhang L, Xiong W, Xiong Y, Liu H and Liu Y: 17 beta-Estradiol promotes vascular endothelial growth factor expression via the Wnt/β-catenin pathway during the pathogenesis of endometriosis. Mol Hum Reprod. 22:526–535. 2016. View Article : Google Scholar : PubMed/NCBI
19	Matsuzaki S and Darcha C: In vitro effects of a small-molecule antagonist of the Tcf/ß-catenin complex on endometrial and endometriotic cells of patients with endometriosis. PLoS One. 8:e616902013. View Article : Google Scholar : PubMed/NCBI
20	Wang S and Ren D: Allicin protects traumatic spinal cord injury through regulating the HSP70/Akt/iNOS pathway in mice. Mol Med Rep. 14:3086–3092. 2016. View Article : Google Scholar : PubMed/NCBI
21	Furuya M, Masuda H, Hara K, Uchida H, Sato K, Sato S, Asada H, Maruyama T, Yoshimura Y, Katabuchi H, et al: ZEB1 expression is a potential indicator of invasive endometriosis. Acta Obstet Gynecol Scand. 96:1128–1135. 2017. View Article : Google Scholar : PubMed/NCBI
22	Panda H, Pelakh L, Chuang TD, Luo X, Bukulmez O and Chegini N: Endometrial miR-200c is altered during transformation into cancerous states and targets the expression of ZEBs, VEGFA, FLT1, IKKbeta, KLF9, and FBLN5. Reprod Sci. 19:786–796. 2012. View Article : Google Scholar : PubMed/NCBI