MicroRNA-135 inhibits initiation of epithelial-mesenchymal transition in breast cancer by targeting ZNF217 and promoting m6A modification of NANOG
ONCOGENE(2022)
摘要
MicroRNAs play significant roles in various malignancies, with breast cancer (BC) being no exception. Consequently, we explored the functional mechanism of miR-135 in the progression of BC. In total, 55 pairs of BC and matched adjacent normal tissues were clinically collected from patients, followed by quantification of miR-135 and zinc finger protein 217 (ZNF217) expression patterns in BC tissues and cells. Accordingly, high ZNF217 expression and low miR-135 expression levels were identified in BC tissues and cells. Subsequently, the expressions of miR-135 and ZNF217 were altered to evaluate their effects on BC cell migration, invasion and EMT initiation. It was found that when ZNF217 was silenced or miR-135 was elevated, BC cell malignant behaviors were significantly inhibited, which was reproduced in nude mice for in vivo evidence. Furthermore, dual-luciferase reporter gene assay revealed the presence of direct binding between miR-135 and ZNF217. Subsequent co-immunoprecipitation, methylated-RNA binding protein immunoprecipitation and photoactivatable ribonucleoside enhanced-crosslinking and immunoprecipitation assays further revealed that ZNF217 could upregulate NANOG by reducing N6-methyladenosine levels via methyltransferase-like 13 (METTL3). Collectively, our findings highlighted the role of the miR-135/ZNF217/METTL3/NANOG axis in the progression of BC, emphasizing potential therapeutic targets ZNF217 silencing and miR-135 upregulation in preventing or treating BC.
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关键词
Cancer,Cell biology,Medicine/Public Health,general,Internal Medicine,Cell Biology,Human Genetics,Oncology,Apoptosis
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