CircRNA-011235 Counteracts The Deleterious Effect of Irradiation Treatment on Bone Mesenchymal Stem Cells by Regulating The miR-741-3p/CDK6 Pathway

CircRNA-011235 通过调节 miR-741-3p/CDK6 通路抵消放射治疗对骨髓间充质干细胞的有害影响

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作者:Xianhui Wen, Hebin Xie, Rong Gui, Xinmin Nie, Dongyong Shan, Rong Huang, Hongyu Deng, Junhua Zhang

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.

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 (CDK6) at the gene and protein levels, respectively.

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

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.

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