MicroRNA let-7g-3p regulates proliferation, migration, invasion and apoptosis of bladder cancer cells by targeting HMGB2

Abstract

To explore the molecular mechanism by which microRNA let-7g-3p regulates biological behaviors of bladder cancer cells. The expression levels of let-7g-3p in bladder cancer and adjacent tissues, normal bladder epithelial cells (HUC cells) and bladder cancer cells (T24, 5637 and EJ cells) were detected using qRT- PCR. T24 cells were transfected with let-7g-3p mimic or inhibitor, and the changes in cell proliferation, migration, invasion, and apoptosis were examined. Transcriptome sequencing was carried out in cells overexpressing let-7g-3p, and the results of bioinformatics analysis, double luciferase reporter gene assay, qRT-PCR and Western blotting confirmed that HMGB2 gene was the target gene of let-7g-3p. The expression of HMGB2 was examined in HUC, T24, 5637 and EJ cells, and in cells with HMGB2 knockdown, the effect of let-7g-3p knockdown on the biological behaviors were observed. qRT-qPCR confirmed that let-7g-3p expression was significantly lower in bladder cancer tissues and cells (P < 0.01). Overexpression of let-7g-3p inhibited cell proliferation, migration and invasion, and promoted cell apoptosis, while let-7g-3p knock-down produced the opposite effects. Bioinformatics and transcriptome sequencing results showed that HMGB2 was the key molecule that mediate the effect of let-7g-3p on bladder cancer cells. Luciferase reporter gene assay, qRT-PCR and Western blotting all confirmed that HMGB2 was negatively regulated by let-7g-3p (P < 0.01). Knocking down HMGB2 could partially reverse the effect of let-7g-3p knockdown on the biological behaviors of the bladder cancer cells. The microRNA let-7g-3p can inhibit the biological behavior of bladder cancer cells by negatively regulating HMGB2 gene.