circrna-011235 counteracts the deleterious effect of irradiation treatment on bone mesenchymal stem cells by regulating the mir-741-3p/cdk6 pathway

Objective: the present work was aimed at uncovering the effect of circrna-011235 (circ-011235) on irradiation-induced bone mesenchymal stem cells (bmscs) injury and its regulatory mechanism, with a view to establish a scientific basis for its possible medical applications. materials and methods: in this experimental study, after irradiation with different doses (0, 2, 4, 6 gy), the relative expression levels of circ-011235, mir-741-3p, and cyclin-dependent kinases 6 (cdk6) were detected in the bmscs, using the real time-quantitative polymerase chain reaction (rt-qpcr). the overexpression effects of circ-011235 and cdk6 on the cell proliferation in irradiation-treated bmscs were measured by the cell counting kit-8 (cck8) assay. and also, their effects on the cell cycle were evaluated by flow cytometry. rt-qpcr and immunoblotting were performed to detect the effects of pcdna-circ-011235 and pcdna-cdk6 on the expression of cyclin d1 and cyclindependent kinases 4 (cdk4) at the gene and protein levels, respectively. results: irradiation treatment elevated the expression of circ-011235 and cdk6, but reduced mir-741-3p expression in the bmscs with a dose-dependent effect. the proliferation of bmscs was significantly inhibited in the irradiation treatment group, while the overexpression of circ-011235 and cdk6 effectively attenuated this inhibition. also, overexpression of circ-011235 and cdk6 elevated the expression of cyclin d1 in irradiation-treated bmscs, but had no significant effect on the cdk4 expression. conclusion: our results demonstrated that circ-011235 up-regulated the expression of cyclin d1 via mir-741-3p/ cdk6 signal pathway, thereby promoting cell cycle progression and proliferation of irradiation-treated bmscs. this finding suggested circ-011235/ mir-741-3p/cdk6 pathway exerted a protective role in the response to irradiation and will be a potential new target for future research on the mechanism involved in the resistance of bmscs to radiation.