Pygo2 as a novel biomarker in gastric cancer for monitoring drug resistance by upregulating MDR1

作者：Dongdong Zhang, Yu Liu, Qiu-Wan Wu, Yahong Zheng, Natasha Mupeta Kaweme, Zhiming Zhang, Mingquan Cai, Youhong Dong · 发表于：Journal of Cancer · 年份：2021 · DOI：10.7150/jca.53356 · 被引用次数：9 · 研究领域：Cancer-related gene regulation、RNA modifications and cancer、Epigenetics and DNA Methylation

, is a well-known multidrug efflux transporter involved in drug resistance development. Pygo2 overexpression has been identified in several cancers. Previous studies have shown that abnormal expression of Pygo2 is related to tumorigenesis, chemoresistance, and tumor progression. In this study, to evaluate the underlying relationship between Pygo2 and MDR1 in GC, we constructed GC drug-resistant cell lines, SGC7901/cis-platinum (DDP), and collected tissue from GC patients' pre-and post-chemotherapy. We found that Pygo2 was overexpressed in GC, especially in GC drug-resistant cell lines and GC patients who underwent neoadjuvant DDP-based chemotherapy. Pygo2 overexpression may precede MDR1 and correlates with MDR1 in GC patients. Furthermore, knock-down of Pygo2 induced downregulation of MDR1 and restored SGC7901/DDP's sensitivity to DDP. Further mechanistic analysis demonstrated that Pygo2 could modulate MDR1 transcription by binding to the MDR1 promoter region and promoting MDR1 activation. The overall findings reveal that Pygo2 may be a promising biomarker for monitoring drug resistance in GC by regulating MDR1.