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
  • 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.
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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