CSB affected on the sensitivity of lung cancer cells to platinum-based drugs through the global decrease of let-7 and miR-29

BACKGROUND: Transcription-coupled nucleotide excision repair (TC-NER) plays a prominent role in the removal of DNA adducts induced by platinum-based chemotherapy reagents. Cockayne syndrome protein B (CSB), the master sensor of TCR, is also involved in the platinum resistant. Let-7 and miR-29 binding sites are highly conserved in the proximal 3′UTR of CSB. METHODS: We conducted immunohistochemisty to examine the expression of CSB in NSCLC. To determine whether let-7 family and miR-29 family directly interact with the putative target sites in the 3′UTR of CSB, we used luciferase reporter gene analysis. To detect the sensitivity of non-small cell lung cancer (NSCLC) cells to platinum-based drugs, CCK analysis and apoptosis analysis were performed. RESULTS: We found that let-7 and miR-29 negatively regulate the expression of CSB by directly targeting to the 3′UTR of CSB. The endogenous CSB expression could be suppressed by let-7 and miR-29 in lung cancer cells. The suppression of CSB activity by endogenous let-7 and miR-29 can be robustly reversed by their sponges. Down-regulation of CSB induced apoptosis and increased the sensitivity of NSCLC cells to cisplatin and carboplatin drugs. Let-7 and miR-29 directly effect on cisplatin and carboplatin sensitivity in NSCLC. CONCLUSIONS: In conclusion, the platinum-based drug resistant of lung cancer cells may involve in the regulation of let-7 and miR-29 to CSB.