MicroRNA‑137 regulates hypoxia‑mediated migration and epithelial‑mesenchymal transition in prostate cancer by targeting LGR4 via the EGFR/ERK signaling pathway

Zhang,Hao; Liang,Fang; Yue,Junmin; Liu,Peng; Wang,Junyong; Wang,Zhaoyang; Li,Hongxing; Cheng,Duo; Du,Jie; Zhang,Kai; Du,Peng

doi:10.3892/ijo.2020.5064

MicroRNA‑137 regulates hypoxia‑mediated migration and epithelial‑mesenchymal transition in prostate cancer by targeting LGR4 via the EGFR/ERK signaling pathway

Authors:
- Hao Zhang
- Fang Liang
- Junmin Yue
- Peng Liu
- Junyong Wang
- Zhaoyang Wang
- Hongxing Li
- Duo Cheng
- Jie Du
- Kai Zhang
- Peng Du
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Affiliations: Department of Urology, Zhengzhou Central Hospital Affiliated to Zhengzhou University (Zhengzhou Central Hospital), Zhengzhou, Henan 450007, P.R. China, Department of Oncology, Zhengzhou Central Hospital Affiliated to Zhengzhou University (Zhengzhou Central Hospital), Zhengzhou, Henan 450007, P.R. China, Department of Urology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing ), Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China
Published online on: May 14, 2020 https://doi.org/10.3892/ijo.2020.5064
Pages: 540-549

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Abstract

MicroRNAs (miRs) serve an integral role in prostate cancer. The present study aimed to investigate the effects and mechanisms of miR‑137 in hypoxia‑mediated migration and epithelial‑mesenchymal transition (EMT). PC3 and DU145 prostate cancer cells were exposed to hypoxia for 24 h, after which the expression of miR‑137 was determined by reverse transcription‑quantitative PCR (RT‑qPCR). The cells were transfected with a miR‑137 mimic or inhibitor, followed by hypoxia exposure. The results demonstrated that hypoxia reduced miR‑137 expression. Further results from the Cell Counting Kit‑8, Cell Death Detection ELISA plus kit, Transwell assay, RT‑qPCR and western blotting assays revealed that the miR‑137 mimic prevented cell proliferation, facilitated apoptosis and repressed cell migration, invasiveness, and expression of N‑cadherin, vimentin and matrix metalloproteinase 2; the miR‑137 inhibitor exerted the opposite effects. A dual‑luciferase reporter assay determined that miR‑137 directly targeted leucine‑rich repeat‑containing G protein‑coupled receptor 4 (LGR4). Additionally, miR‑137 negatively regulated the epidermal growth factor receptor/extracellular signal‑regulated kinase (EGFR/ERK) signaling pathway by targeting LGR4. LGR4 silencing or EGFR/ERK inhibition abolished the effects of miR‑137 inhibitor on cell migration and EMT. In conclusion, by targeting LGR4 via the EGFR/ERK signaling pathway, miR‑137 inhibited prostate cancer cell migration and EMT.

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