2. Academic Validation
  3. PPM1G promotes autophagy and progression of pancreatic cancer via upregulating HMGB1

PPM1G promotes autophagy and progression of pancreatic cancer via upregulating HMGB1

  • Cell Signal. 2024 Aug 7:111342. doi: 10.1016/j.cellsig.2024.111342.
Mingyang Song 1,  Min Xu 2,  Qi Zhang 3,  Tingyu Fan 3,  Jiajia Xu 4,  Cheng Hang 5,  Cuie Cheng 6,  Xilong Ou 7,  Chen Gong 8,  Qin Lu 9
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China; Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
  • 2 Department of Human Anatomy, School of Medicine, Southeast University, Nanjing 210009, China.
  • 3 Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
  • 4 Department of Clinical Pathology, Zhongda Hospital, Southeast University, Nanjing 210009, China.
  • 5 Department of Gastroenterology, Taicang Affiliated Hospital of Soochow University, The First People's Hospital of Taicang, Jiangsu 215400, China.
  • 6 Department of Gastroenterology, Affiliated Changshu Hospital of Nantong University, Suzhou 215500, China.
  • 7 Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China. Electronic address: ouxilong2021@163.com.
  • 8 Department of Gastroenterology, Taicang Affiliated Hospital of Soochow University, The First People's Hospital of Taicang, Jiangsu 215400, China. Electronic address: gongchen@suda.edu.cn.
  • 9 Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China. Electronic address: luqin81287@163.com.
PMID: 39121976 DOI: 10.1016/j.cellsig.2024.111342
Abstract

Pancreatic Cancer remains one of the most aggressive and lethal malignancies worldwide, with a dismal 5-year relative survival rates of only 12%. Therefore, it is urgent to discover the key molecular markers to improve the therapeutic outcomes in pancreatic Cancer. Herein, we first demonstrated that PPM1G is upregulated in pancreatic Cancer and that PPM1G depletion decreases pancreatic Cancer cell growth in vitro and in vivo. High PPM1G expression was linked to short overall survival of pancreatic Cancer patients, which was further validated in the TCGA database. Moreover, by detecting Beclin 1, LC3-II, and SQSTM1/p62 expressions and observing autolysosome under transmission electron microscope, we discovered that PPM1G is a novel positive regulator of macroautophagy/Autophagy. Furthermore, by using immunoprecipitation-mass spectrometry (IP-MS) analysis and following systemic Molecular Biology experiment, we demonstrated PPM1G promotes the Autophagy and proliferation of pancreatic Cancer by directly upregulating HMGB1. Additionally, patients with both high PPM1G and high HMGB1 exhibited poorer prognosis in our cohort. This study preliminarily investigated the possibility of PPM1G as a potential therapeutic target and prognostic biomarker in pancreatic Cancer patients.

Keywords

Autophagy; HMGB1; PPM1G; Pancreatic cancer; Progression.

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