Profiling of Autophagy-Associated microRNAs in the Osteosarcoma Cell Line of U2OS.

Abstract

Autophagy is a cellular process that plays a role in the destruction of proteins and organelles. It has been shown that impaired autophagic flux triggers canceration, infectious disease, and neurodegenerative diseases. It has been suggested that tumor formation is inhibited by autophagy that reduces oxidative stress and recycles damaged organelles. microRNAs are 17-25 bp in length, single-stranded, and noncoding small RNAs that play roles in the regulation of metabolic gene expression at the post-transcriptional level. Osteosarcoma is an aggressive bone cancer that affects mainly children and adolescents. The current article aims to profile autophagy-associated miRNAs in osteosarcoma cell lines and to examine the therapeutical potentials of these miRNAs by suppressing their expressions with Adriamycin and Rapamycin. We used fluidigm dynamic array nanofluidic chip 96.96 for mRNA expression assay in osteosarcoma cell line U2OS. It was probed that after the suppression of autophagy-associated miRNAs by adriamycin and rapamycin, while most of the miRNAs were down-regulated in osteosarcoma cell lines, some miRNAs' expressions, such as miR-3141, miR-4296, miR-133b, and miR-720, were strikingly increased. Rapamycin and adriamycin, mTOR inhibitors, stir autophagic machinery, which results in decreased cell survival. Together, we propose that the expressions of miR-3141, miR-4296, miR-133b, and miR-720 might exacerbate the pathogenesis of osteosarcoma; therefore, the suppression of these miRNAs with the loss-offunction approaches could be an appropriate strategy that is worth testing in osteosarcoma.