miR-539-5p inhibits proliferation and invasion of gallbladder cancer cells by targeting BACH1

Abstract

Background: Gallbladder cancer (GBC) is a common biliary tract malignancy worldwide, with no definite molecular-targeted treatment. Previous studies have shown that miR-539-5p was observed to be aberrantly expressed in multiple tumors and was associated with the occurrence and progression of human cancers. However, the functional role and exact mechanism of miR-539-5p in GBC progression remain barely known.Methods: The expression of miR-539-5p and BACH1 in GBC tissues and cell lines was detected by qRT-PCR. Western blotting was utilized to detect the protein level of BACH1. CCK-8 assay, colony formation assay, and Transwell assay was employed to evaluate GBC cell proliferation and invasion. Dual-luciferase reporter gene assay was utilized to verify the target relationship between miR-539-5p and BTB domain and CNC homolog 1 (BACH1). Xenograft tumor experiments were conducted on nude mice to confirm antitumor effect of miR-539-5p on GBC in vivo.Results: Our results showed that miR-539-5p was downregulated in GBC tissues and cell lines. Overexpression of miR-539-5p significantly suppressed the proliferation and invasion abilities of GBC cells. Dual-luciferase reporter gene assay confirmed that BACH1 was a target gene of miR-539-5p. Moreover, knockdown of BACH1 exhibited anti-proliferation and anti-invasion effects on GBC cells. Mechanistically, miR-539-5p suppressed the malignant behaviors of GBC cells, which were largely counteracted by the overexpression of BACH1. In vivo experiments, miR-539-5p overexpression tremendously repressed GBC tumor growth.Conclusion: miR-539-5p inhibited GBC progression via directly targeting BACH1, which can be served as potential treatment targets against the progression of GBC.