CircRNA-016901 silencing attenuates irradiation-induced injury in bone mesenchymal stem cells via regulating the miR-1249-5p/HIPK2 axis.

Abstract

Currently, bone marrow transplantation remains the basic treatment for various hematological tumors and irradiation is one of the most important pretreatment methods. However, irradiation pretreatment may result in damage to bone mesenchymal stem cells (BMSCs). The present study aimed to investigate the effect of circular RNA-016901 (circ-016901) on the injury of irradiation-induced BMSCs and the underlying mechanism. The expression levels of circ-016901, microRNA-1249-5p (miR-1249-5p) and homeodomain interacting protein kinase 2 (HIPK2) in irradiation-induced mouse BMSCs at various irradiation doses were detected via reverse transcription-quantitative PCR (RT-qPCR). The effect of circ-016901 on cell proliferation was examined using Cell Counting Kit-8 assays following silencing or overexpression of circ-016901. Cell apoptosis was detected by flow cytometry and caspase-3/7 activity. The expression of autophagy-related markers, including Beclin-1 and LC3-II/I, was detected at the mRNA and protein levels by RT-qPCR and western blotting, respectively. Irradiation treatment upregulated the expression of circ-016901 and HIPK2 and downregulated miR-1249-5p expression. The expression levels of LC3-II/I and Beclin-1 in BMSCs were downregulated in a dose-dependent manner. Silencing of circ-016901 promoted proliferation of irradiation-induced BMSCs and attenuated irradiation-induced apoptosis. Moreover, silencing of circ-016901 elevated the expressions of LC3-II/I and Beclin-1 in irradiation-induced BMSCs. Similar results were obtained with miR-1249-5p overexpression and HIPK2 silencing. These results demonstrated that circ-016901 silencing attenuated injury in irradiation-induced mouse BMSCs by regulating the miR-1249-5p/HIPK2 axis, providing a novel target for future research on the mechanism of radiation resistance in BMSCs.