Brother of regulator of imprinted sites inhibits cisplatin-induced DNA damage in non-small cell lung cancer

ABSTRACT: Cisplatin (DDP) chemotherapy is the primary modality of treatment for non-small cell lung cancer (NSCLC). However, due to the occurrence of DDP resistance, only a limited number of patients benefit from this treatment regimen. Brother of Regulator of Imprinted Sites (BORIS) is expressed elevated in NSCLC. Whether BORIS is involved in the DDP resistance of NSCLC is currently undetermined. The association between BORIS expression and overall survival rate of 156 patients with NSCLC who received DDP chemotherapy was analyzed in the present study. In order to investigate the function of BORIS in DDP chemotherapy, BORIS was silenced or overexpressed in four NSCLC cell lines. The cell viabilities, apoptosis and DNA damage induced by DDP were evaluated in these cell lines. In addition, the regulations of DNA repair genes were assessed, including POLH, ERCC1, BRCA1, MSH6 and XPA. The present study demonstrated that high BORIS expression was associated with decreased overall survival rate in patients with NSCLC who received DDP chemotherapy. The patients who benefited and went into remission following DDP therapy expressed a relatively low level of BORIS, suggesting the potential function of BORIS in DDP resistance. Cell experiments revealed that NSCLC cells that had a higher proliferation rate and resisted DDP treatment expressed a relatively higher level of BORIS. Knockdown of BORIS in NSCLC cells induced DNA damage; inhibiting cell proliferation and sensitizing cells to DDP treatment. In contrast, BORIS overexpression suppressed DDP-induced DNA damage. Notably, the mismatch repair factor mutS homolog 6 (MSH6) was regulated by BORIS, indicating its association with BORIS-associated DDP resistance in NSCLC. The findings of the present study suggest that BORIS suppresses DNA damage and promotes the progression of NSCLC and DDP resistance. The present study indicates the potential application of BORIS in NSCLC therapy and prognosis.

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC7509674 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature