PPM1G promotes autophagy and progression of pancreatic cancer via upregulating HMGB1

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2024-08-08 DOI:10.1016/j.cellsig.2024.111342

{"title":"PPM1G promotes autophagy and progression of pancreatic cancer via upregulating HMGB1","authors":"","doi":"10.1016/j.cellsig.2024.111342","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular signalling","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0898656824003103","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

PPM1G 通过上调 HMGB1 促进自噬和胰腺癌的进展。

胰腺癌仍然是全球最具侵袭性和致命性的恶性肿瘤之一，5 年相对生存率仅为 12%，令人沮丧。因此，发现关键分子标记物以改善胰腺癌的治疗效果迫在眉睫。在本文中，我们首次证明了 PPM1G 在胰腺癌中的上调，并且 PPM1G 的缺失会降低胰腺癌细胞在体外和体内的生长。PPM1G的高表达与胰腺癌患者总生存期短有关，这一点在TCGA数据库中得到了进一步验证。此外，通过检测 Beclin 1、LC3-II 和 SQSTM1/p62 的表达以及在透射电子显微镜下观察自溶体，我们发现 PPM1G 是一种新型的大自噬/自噬正调控因子。此外，通过免疫沉淀-质谱（IP-MS）分析和系统分子生物学实验，我们证明了PPM1G通过直接上调HMGB1促进胰腺癌的自噬和增殖。此外，在我们的队列中，高 PPM1G 和高 HMGB1 患者的预后较差。本研究初步探讨了 PPM1G 作为胰腺癌患者潜在治疗靶点和预后生物标志物的可能性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.

文献相关原料

公司名称	产品信息	采购帮参考价格