@article { author = {Wen, Xianhui and Xie, Hebin and Gui, Rong and Nie, Xinmin and Shan, Dongyong and Huang, Rong and Deng, Hongyu and Zhang, Junhua}, title = {CircRNA-011235 Counteracts The Deleterious Effect Of Irradiation Treatment On Bone Mesenchymal Stem Cells By Regulating The MiR-741-3p/CDK6 Pathway}, journal = {Cell Journal (Yakhteh)}, volume = {24}, number = {1}, pages = {15-21}, year = {2022}, publisher = {Royan Institute, Iranian Academic Center for Education Culture and Research (ACECR)}, issn = {2228-5806}, eissn = {2228-5814}, doi = {10.22074/cellj.2022.7697}, abstract = {Objective: The present work was aimed at uncovering the effect of circRNA-011235 (circ-011235) on irradiation-inducedbone 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 nosignificant 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.}, keywords = {Bone Mesenchymal Stem Cell,CDK6,Cell cycle,Irradiation}, url = {https://www.celljournal.org/article_251724.html}, eprint = {https://www.celljournal.org/article_251724_f113bd45974a90e08b99f18a3ab447ec.pdf} }