Long noncoding RNA LINC02582 acts downstream of miR-200c to promote radioresistance through CHK1 in breast cancer cells
Wang, Zheng, Li, Tian, Lin, Liang, Sun, Xu, Zheng, Liu, Ji, Bu, Yuan (2019) Long noncoding RNA LINC02582 acts downstream of miR-200c to promote radioresistance through CHK1 in breast cancer cells Cell Death Dis (IF: 9) 10(10) 764Abstract
Radiotherapy is essential to treat breast cancer and microRNA (miRNA) miR-200c is considered as a radiosensitizer of breast cancer. However, the molecular mechanisms by which miR-200c regulates radiosensitivity remain largely unknown. In the present study, we showed that induction of miR-200c led to widespread alteration in long noncoding RNA (lncRNA) expression in breast cancer cells. We identified lncRNA LINC02582 as a target of miR-200c. Inhibition of LINC02582 expression increased radiosensitvity, while overexpression of LINC02582 promoted radioresistance. Mechanistically, LINC02582 interacts with deubiquitinating enzyme ubiquitin specific peptidase 7 (USP7) to deubiquitinate and stabilize checkpoint kinase 1 (CHK1), a critical effector kinase in DNA damage response, thus promoting radioresistance. Furthermore, we detected an inverse correlation between the expression of miR-200c vs. LINC02582 and CHK1 in breast cancer samples. These findings identified LINC02582 as a downstream target of miR-200c linking miR-200c to CHK1, in which miR-200c increases radiosensitivity by downregulation of CHK1.
Links
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787210http://www.ncbi.nlm.nih.gov/pubmed/31601781
http://dx.doi.org/10.1038/s41419-019-1996-0