Passenger strand of miR-145-3p acts as a tumor-suppressor by targeting MYO1B in head and neck squamous cell carcinoma.

Abstract

Analysis of the microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC) based on RNA sequencing showed that dual strands of pre-miR-145 (miR-145-5p, guide strand; and miR-145-3p, passenger strand) were significantly reduced in cancer tissues. In miRNA biogenesis, passenger strands of miRNAs are degraded and have no biological activities in cells. The aims of this study were to investigate the functional significance of the passenger strand of miR-145 and to identify miR-145-3p-regulated oncogenic genes in HNSCC cells. Expression levels of miR-145-5p and miR-145-3p were significantly downregulated in HNSCC tissues and cell lines (SAS and HSC3 cells). Ectopic expression of miR-145-3p inhibited cancer cell proliferation, migration and invasion, similar to miR-145-5p, in HNSCC cells. Myosin 1B (MYO1B) was directly regulated by miR-145-3p, and knockdown of MYO1B by siRNA inhibited cancer cell aggressiveness. Overexpression of MYO1B was confirmed in HNSCC clinical specimens by analysis of protein and mRNA levels. Interestingly, high expression of MYO1B was associated with poor prognosis in patients with HNSCC by analysis of The Cancer Genome Atlas database (p=0.00452). Our data demonstrated that the passenger strand of miR-145 acted as an antitumor miRNA through targeting MYO1B in HNSCC cells. The involvement of dual strands of pre-miR-145 (miR-145-5p and miR-145-3p) in the regulation of HNSCC pathogenesis is a novel concept in present RNA research.