2. Academic Validation
  3. 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. cqlin@seu.edu.cn.
  • 6 Shenzhen Research Institute, Southeast University, 19 Gaoxin South 4th Road, Nanshan District, Shenzhen, 518063, China. cqlin@seu.edu.cn.
  • 7 Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, School of Life Science and Technology, Southeast University, Nanjing, 210096, China. cqlin@seu.edu.cn.
  • 8 Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing, 210096, China. zjluo@seu.edu.cn.
  • 9 Shenzhen Research Institute, Southeast University, 19 Gaoxin South 4th Road, Nanshan District, Shenzhen, 518063, China. zjluo@seu.edu.cn.
  • 10 Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Life Science and Technology, Southeast University, Nanjing, 210096, China. zjluo@seu.edu.cn.
  • # Contributed equally.
PMID: 36371602 DOI: 10.1038/s41418-022-01085-x
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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