The role of miR-125b-5p- AKT serine/threonine kinase 1 axis in osteosarcoma

Abstract

Osteosarcoma is a most frequent primary solid malignant disease of bone, mainly affecting children and adolescents. Although several factors are involved in osteosarcoma development, genetic factors seem to play a chief role in the induction and advancement of osteosarcoma. AKT1 is an oncogenic protein that is highly deregulated in a variety of human malignancies including osteosarcoma. By the discovery of small RNA molecules called miRNAs, our understanding of post-transcriptional regulation of molecular mechanisms is considerably evolved. Also, the role of miR-125b-5p in osteosarcoma still muchly remains controversial. Specifically, miR-125b-5p- AKT serine/threonine kinase 1 (AKT1) axis has not been previously reported in osteosarcoma. Accordingly, in this particular study, for the first time, we reveal the miR-125b-5p-mediated regulation of AKT1 in osteosarcoma development. U2-OS osteosarcoma cells were used as an osteosarcoma cell line model. To ectopically overexpress miR-125b-5p in U2-OS osteosarcoma cells, synthetic miRNA mimics targeting miR-125b-5p were used. Quantitative RT-PCR method was used for the analysis of gene expressions. Significant overexpression of miR-125b-5p was observed following 72 h of mimic transfections (p < 0.0001). As a result, expression of AKT1 gene was found to be differentially reduced in cells treated with miR-125b-5p mimics in contrast to cells treated with scramble control and/or blank (p = 0.0205). Collectively, present findings suggest that miR-125b-5p is a strong tumor suppressor miRNA for osteosarcoma tumorigenesis as it regulates the -expression of tumor promotor AKT1 gene and might be used further therapeutic intervention to osteosarcoma.