MicroRNA-154 as a prognostic factor in bladder cancer inhibits cellular malignancy by targeting RSF1 and RUNX2

Recent studies have demonstrated that microRNA-154 (miR-154) is involved in tumorigenesis, progression, invasion and metastasis in several types of human cancer. However, whether it plays a role in bladder cancer (BC) is unclear. The aim of the present study was to determine miR-154 levels in human BC tissues and investigate the correlation between miR-154 levels and clinicopathological characteristics as well as patient outcome. Using RT-qPCR, we found that the expression levels of miR-154 were significantly lower in BC tissues compared to adjacent normal tissues. We also demonstrated that downregulation of miR-154 was associated with advanced clinicopathological features and worse prognoses for patients with BC. Using a variety of integrated approaches, we demonstrated that both runt-related transcription factor 2 (RUNX2) and remodeling and spacing factor 1 (RSF1) were miR-154 targets. Notably, there was an inverse correlation between RSF1, RUNX2 and miR-154 expression in BC tissues. The biological functions of miR-154 were examined in vitro using Cell Counting Kit-8 (CCK-8), wound healing, and Transwell assays with T24 human bladder carcinoma cells transfected with miR-154 mimics or negative controls. These assays demonstrated that miR-154 significantly suppressed proliferation, migration and invasion of T24 cells (P<0.05). Furthermore, overexpression of RSF1 and RUNX2 rescued miR-154-induced inhibition of these aggressive behaviors. Our results indicated that miR-154, and its downstream targets RSF1 and RUNX2, are promising options for future BC therapies.