MicroRNA-448 targets SATB1 to reverse the cisplatin resistance in lung cancer via mediating Wnt/β-catenin signalling pathway

Abstract

This study aims to examine whether miR-448 reverses the cisplatin (DDP) resistance in lung cancer by modulating SATB1. QRT-PCR and immunohistochemistry were used to examine the miR-448 and SATB1 expressions in DDP-sensitive and -resistant lung cancer patients. A microarray was used to investigate the cytoplasmic/nucleic ratio (C/N ratios) of genes in A549 cells targeted by miR-448, followed by Dual-luciferase reporter gene assay. A549/DDP cells were transfected with miR-448 mimics/inhibitors with or without SATB1 siRNA followed by MTT assay, Edu staining, flow cytometry, qRT-PCR and western blotting. MiR-448 was lower but SATB1 was increased in DDP-resistant patients and A549/DDP cells. And the patients showed low miR-448 expression or SATB1 positive expression had poor prognosis. SATB1, as a target gene with higher C/N ratios (>1), was found negatively regulated by miR-448. Besides, miR-448 inhibitors increased resistance index of A549/DDP cells, promoted cell proliferation, increased cell distribution in S phrase, declined cell apoptosis and activated Wnt/β-catenin pathway. However, SATB1 siRNA could reverse the above effect caused by miR-448 inhibitors. MiR-448 targeting SATB1 to counteract the DDP resistance of lung cancer cells via Wnt/β-catenin pathway.

Keywords: SATB1; cisplatin; drug resistance; lung cancer; miR-448.