ZNF300 promotes chemoresistance and aggressive behaviour in non‐small‐cell lung cancer. (19th October 2020)

• Record Type: Journal Article
• Authors: Yu, Shilong; Ao, Zhi; Wu, Yi; Song, Liyuan; Zhang, Peng; Li, Xiaokang; Liu, Min; Qian, Pin; Zhang, Ruijie; Li, Xihua; Chen, Yan; Wang, Xuanbin; Wang, Xianhui; Ruan, Xuzhi; Qian, Guisheng; Ji, Fuyun
• Is Part Of: Cell proliferation. Volume 53:Number 11(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-10-19
• Subjects: cell cycle -- chemoresistance -- differentiation -- NSCLC -- ZNF300; Cell proliferation -- Periodicals; 571.84
• DOI: 10.1111/cpr.12924
• Languages: English
• ISSNs: 0960-7722

Abstract

Abstract: Objectives: Chemoresistance induced by cisplatin has become the major impediment to lung cancer chemotherapy. This study explored the potential chemoresistant genes and underlying mechanisms of chemoresistance in NSCLC. Materials and methods: Gene expression profile was integrated with DNA methylation profile to screen the candidate chemoresistant genes. Bioinformatic analysis and immunohistochemistry were used to analyse the association of a candidate gene with the characteristics of NSCLC patients. Recombinant lentivirus vectors were utilized to overexpress or silence candidate gene. Microarrays and immunoblotting were applied to explore the downstream targets of candidate gene. Xenograft models were established to validate the findings in vitro. Results: An increased ZNF300 expression was detected in three chemoresistant cell lines of NSCLC, and the higher expression of ZNF300 was associated with poor OS of NSCLC patients. Cells with upregulated ZNF300 presented chemoresistance and enhanced aggressive growth compared to cells with downregulated ZNF300. ZNF300 inhibited MAPK/ERK pathways and activated CDK1 through inhibiting WEE1 and MYT1 and modulating MYC/AURKA/BORA/PLK1 axis. ICA and ATRA improved the anti‐tumour effect of cisplatin on chemoresistant cells by inducing differentiation. Conclusions: ZNF300 promotes chemoresistance and aggressive behaviour of NSCLC through regulation of proliferation and differentiation by downregulating MAPK/ERK pathways and regulation of slow‐cycling phenotype via activating CDK1 by inhibiting WEE1/MYT1 and modulating MYC/AURKA/BORA/PLK1 axis. Cisplatin, combined with ATRA and ICA, might be beneficial in chemoresistant cases of NSCLC. Abstract : ZNF300 mediates chemoresistance of NSCLC. ZNF300 promotes aggressive growth of tumour cells correlating to poor prognosis of patients with NSCLC. ZNF300 inhibits MAPK/ERK signalling pathway to suppress proliferation and differentiation of chemoresistant cells. ZNF300 activates CDK1 by inhibiting WEE1 and MYT1 and modulating MYC/AURKA/BORA/PLK1 axis to regulate cell cycle of chemoresistant cells. ICA and ATRA improves anti‐tumour effect of cisplatin on chemoresistant cells by inducing differentiation.