miR-433 suppresses tumor progression via Smad2 in non-small cell lung cancer

Abstract The role of transforming growth factor beta (TGF-β) in lung cancer is well known. TGF-β-mediated cellular proliferation and angiogenesis through similar to mothers against decapentaplegic homolog 2 (Smad2) protein has also been well elucidated. Smad2 is a predicted target for a microRNAs, namely miR-433. microRNAs are a significant class of non-coding RNAs which play an important role in epigenetic regulation. Here, we show that miR-433 directly binds to Smad2, which is shown to be upregulated in non-small cell lung carcinomas (NSCLC). miR-433 expression is downregulated in NSCLC tissues and cells. Overexpression of miR-433 is associated with decreased expression of proteins - namely Cyclin D1, MMP-2/TIMP-2, and MMP-9, and consequently reduced cell proliferation and invasion phenotypes. Complementation of miR-433 leads to rescue of these disrupted phenotypes. miR-433 mediates its action via Smad2 and Id-1. miR-433 may be a candidate worth further exploration for its prognostic and therapeutic potential in NSCLC.