Chemotherapy resistance in non-small lung cancer regulate by holliday junction-recognizing protein through YAP1/NDRG1 transcriptional axis

Abstract

Lung cancer remains the leading cause of cancer death and often diagnosed at an advanced stage because of its speedy growth and early tendency to spread to other organs and tissues The objective of this study focuses on exploring the role of the HJURP/YAP1/NDRG1 transcriptional regulation axis in NSCLC. We observed significantly increased upregulation of HJURP expression levels in NSCLC tissues. Loss of function experiments identified that HJURP promotes NSCLC cells proliferation and decreases chemo-sensitivity. HJURP could affect the level of ubiquitination modification of YAP1 protein and then regulate its downstream transcriptional activity. Mechanistically, we found that YAP1 positively regulates NDRG1 transcription by binding the promoter region of the NDRG1 gene, and HJURP/YAP1/NDRG1 axis could affect chemotherapy sensitivity in NSCLC. Taken together, these findings provide insights into the HJURP as a tumor promoter in NSCLC via the activation of YAP1/NDRG1 axis, indicating HJURP may be a promising therapeutic target for NSCLC.