MicroRNA-153-3p suppresses retinoblastoma cell growth and invasion via targeting the IGF1R/Raf/MEK and IGF1R/PI3K/AKT signaling pathways

Mounting evidence has demonstrated that microRNAs (miRNAs or miRs) play significant roles in various types of human tumors, including retinoblastoma (RB). However, the biological role and regulatory mechanisms of miRNAs in RB remain to be fully elucidated. The present study was designed to identify the regulatory effects of miRNAs in RB and the underlying mechanisms. Differentially expressed miRNAs in RB tissue were screened out based on the Gene Expression Omnibus (GEO) dataset, GSE7072, which revealed that miR-153 in particular, displayed the highest fold change in expression. It was identified that miR-153 was significantly downregulated in RB tissues, and its downregulation was closely associated with a larger tumor base and differentiation. Functional analysis revealed that the overexpression of miR-153 inhibited RB cell proliferation, migration and invasion, and promoted the apoptosis of WERI-RB-1 and Y79 cells. In addition, insulin-like growth factor 1 receptor (IGF1R) was identified as a target of miR-153 in RB cells. More importantly, it was demonstrated that miR-153 upregulation inhibited the expression of its target gene, IGF1R, which inhibited the activation of the Raf/MEK and PI3K/AKT signaling pathways. Collectively, the present study demonstrates for the first time, to the best of our knowledge, that miR-153 functions as a tumor suppressor in RB by targeting the IGF1R/Raf/MEK and IGF1R/PI3K/AKT signaling pathways. Collectively, the findings presented herein demonstrate that miR-153 targets IGF1R and blocks the activation of the Raf/MEK and PI3K/AKT signaling pathway, thus preventing the progression of RB. Thus, this miRNA may serve as a novel prognostic biomarker and therapeutic target for RB.