Upregulation of MiR-183-5p is Responsible for the Promotion of Apoptosis and Inhibition of the Epithelial-mesenchymal Transition, Proliferation, Invasion and Migration of Human Endometrial Cancer Cells by Downregulating Ezrin
Overview
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Endometrial cancer is a life‑threatening malignancy that affects women all over the world, and it has an increasing incidence. MicroRNAs (miRNAs/miRs) have been reported to be involved in cellular activities in endometrial cancer. The present study aimed to examine the effects of miR‑183‑5p on the epithelial‑mesenchymal transition (EMT), proliferation, invasion, migration and apoptosis of human endometrial cancer cells by targeting Ezrin. Primary endometrial cancer tissues and adjacent normal tissues were obtained for the investigation. The protein expression of Ezrin in tissues was detected by immunohistochemistry. The expression level of miR‑183‑5p and the mRNA and protein expression levels of Ezrin and EMT‑associated genes were determined by reverse transcription‑quantitative polymerase chain reaction and western blot analyses. Endometrial cancer cells were treated with miR‑183‑5p inhibitors, small interfering RNA targeting Ezrin or miR‑183‑5p inhibitors. Cell proliferation, cell cycle, apoptosis, migration and invasion were then evaluated using an MTT assay, flow cytometry, scratch test and Transwell assay, respectively. Compared with normal adjacent tissues, the expression of miR‑183‑5p was decreased in endometrial cancer tissues, and the expression of Ezrin was significantly increased in endometrial cancer tissues. The protein expression of Ezrin was correlated with the severity and poor prognosis of endometrial cancer. Notably, the target prediction program and the luciferase reporter gene assay confirmed that miR‑183‑5p targeted and negatively regulated the expression of Ezrin. In vivo experiments revealed that the increased expression of miR‑183‑5p and decreased expression of Ezrin inhibited EMT, cell proliferation, migration and invasion, but promoted cell apoptosis in Ishikawa cells. These results suggested that the upregulated expression of miR‑183‑5p promoted apoptosis and suppressed the EMT, proliferation, invasion and migration of human endometrial cancer cells by downregulating Ezrin.
Advances in MiRNAs Involved in Endometrial Carcinoma.
He Y, Liao K, Peng H, Zou X, Guo Z Comb Chem High Throughput Screen. 2024; 28(1):3-11.
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Discovery of novel microRNA mimic repressors of ribosome biogenesis.
Bryant C, McCool M, Rosado Gonzalez G, Abriola L, Surovtseva Y, Baserga S Nucleic Acids Res. 2024; 52(4):1988-2011.
PMID: 38197221 PMC: 10899765. DOI: 10.1093/nar/gkad1235.
MicroRNA-183 cluster: a promising biomarker and therapeutic target in gastrointestinal malignancies.
Zheng Y, Sukocheva O, Tse E, Neganova M, Aleksandrova Y, Zhao R Am J Cancer Res. 2024; 13(12):6147-6175.
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Identification of Endometrial Cancer-Specific microRNA Biomarkers in Endometrial Fluid.
Yang J, Barkley J, Bhattarai B, Firouzi K, Monk B, Coonrod D Int J Mol Sci. 2023; 24(10).
PMID: 37240034 PMC: 10218319. DOI: 10.3390/ijms24108683.
Gupta M, Walters B, Katsara O, Granados Blanco K, Geter P, Schneider R Proc Natl Acad Sci U S A. 2023; 120(15):e2207898120.
PMID: 37014850 PMC: 10104532. DOI: 10.1073/pnas.2207898120.