Downregulation of KHSRP enhances carboplatin sensitivity in non-small cell lung cancer.

[BACKGROUND] Carboplatin resistance represents a critical therapeutic challenge in non-small cell lung cancer (NSCLC) treatment. Although KHSRP has been implicated in lung cancer progression, its molecular mechanisms and impacts on chemotherapy sensitivity remain elusive. Notably, KHSRP has the capacity to activate the transcription of HMGB1, an oncogene known to influence chemotherapy sensitivity. However, it remains to be determined whether KHSRP affects chemotherapy response in NSCLC via HMGB1.

[METHODS] KHSRP expression in NSCLC cells was analyzed using qRT-PCR. Cell proliferation, apoptosis, and migration were evaluated using colony formation, flow cytometry and wound healing assays. A luciferase reporter assay was conducted to assess whether KHSRP transcriptionally regulates HMGB1. Additionally, A549 cell xenografts were established in nude mice to investigate the tumor growth-promoting effects of KHSRP in vivo.

[RESULTS] KHSRP expression was notably elevated in NSCLC cells. Overexpression of KHSRP remarkably promoted A549 cell proliferation, migration, and epithelial-mesenchymal transition (EMT); while KHSRP knockdown exhibited the opposite effects. Mechanically, KHSRP notably promoted the transcription of HMGB1 and upregulated its expression in A549 cells. Importantly, deficiency of KHSRP remarkably enhanced the suppressive effects of carboplatin on A549 cell proliferation, migration, EMT and HMGB1 expression. Meanwhile, in vivo experiments demonstrated that downregulation of KHSRP potentiated the inhibitory effect of carboplatin on tumor growth in tumor-bearing nude mice.

[CONCLUSION] These findings demonstrate that silencing of KHSRP enhances the drug sensitivity of carboplatin in NSCLC, potentially mediated through the inhibition of HMGB1. Targeting KHSRP may represent a promising therapeutic strategy to improve chemotherapy efficacy in NSCLC.