1. Academic Validation
  2. QSER1 preserves the suppressive status of the pro-apoptotic genes to prevent apoptosis

QSER1 preserves the suppressive status of the pro-apoptotic genes to prevent apoptosis

  • Cell Death Differ. 2022 Nov 12. doi: 10.1038/s41418-022-01085-x.
Xiru Zhao # 1 Ke Fang # 1 Xiaoxu Liu # 1 Ruihuan Yao 1 Min Wang 1 Fanfan Li 1 Shaohua Hao 1 Jingjing He 1 Yan Wang 1 Menghan Fan 1 Wei Huang 2 Yiping Li 3 Chun Gao 4 Chengqi Lin 5 6 7 Zhuojuan Luo 8 9 10
Affiliations

Affiliations

  • 1 Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing, 210096, China.
  • 2 Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
  • 3 Department of Pathology, School of Medicine, Southeast University, Nanjing, 210009, China.
  • 4 Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, 100029, China.
  • 5 Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing, 210096, China. [email protected].
  • 6 Shenzhen Research Institute, Southeast University, 19 Gaoxin South 4th Road, Nanshan District, Shenzhen, 518063, China. [email protected].
  • 7 Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, School of Life Science and Technology, Southeast University, Nanjing, 210096, China. [email protected].
  • 8 Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing, 210096, China. [email protected].
  • 9 Shenzhen Research Institute, Southeast University, 19 Gaoxin South 4th Road, Nanshan District, Shenzhen, 518063, China. [email protected].
  • 10 Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Science and Technology, Southeast University, Nanjing, 210096, China. [email protected].
  • # Contributed equally.
Abstract

Activation of the pro-apoptotic genes by the p53 family is a critical step in induction of Apoptosis. However, the molecular signaling underlying their suppression remains largely unknown. Here, we report a general role of QSER1 in preventing Apoptosis. QSER1 is widely up-regulated in multiple cancers, and its up-regulation correlates with poor clinic outcomes. QSER1 knockdown significantly promotes Apoptosis in both p53 wild type and mutant Cancer cells. Interestingly, we show that QSER1 and p53 occupy distinct cis-regulatory regions in a common subset of the pro-apoptotic genes, and function antagonistically to maintain their proper expression. Furthermore, we identify a key regulatory DNA element named QSER1 binding site in PUMA (QBP). Deletion of QBP de-represses PUMA and induces Apoptosis. Mechanistically, QSER1 functions together with SIN3A to suppress PUMA in a p53-dependent and -independent manner, suggesting that QSER1 inhibition might be a potential therapeutic strategy to induce Apoptosis in cancers.

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