Aspartoacylase suppresses prostate cancer progression by blocking LYN activation  

作　　者：Hong Weng Kang-Ping Xiong Wang Wang Kai-Yu Qian Shuai Yuan Gang Wang Fang Yu Jun Luo Meng‑Xin Lu Zhong‑Hua Yang Tao Liu Xing Huang Hang Zheng Xing-Huan Wang 

机构地区：[1]Department of Urology,Zhongnan Hospital of Wuhan University,Wuhan 430071,China [2]Center for Evidence‑Based and Translational Medicine,Zhongnan Hospital of Wuhan University,Wuhan 430071,China [3]Department of Biological Repositories,Zhongnan Hospital of Wuhan University,Wuhan 430071,China [4]Hubei Key Laboratory of Tumor Biological Behaviors,Wuhan 430071,China [5]Department of Pathology,Zhongnan Hospital of Wuhan University,Wuhan 430071,China [6]Center for Pathology and Molecular Diagnostics,Wuhan University,Wuhan 430071,China [7]Wuhan Research Center for Infectious Diseases and Cancer,Chinese Academy of Medical Sciences,Wuhan 430071,China

出　　处：《Military Medical Research》2024年第2期180-205,共26页军事医学研究（英文版）

基　　金：supported by the Science and Technology Department of Hubei Province Key Project(YYXKNL2022001);the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2020-PT320-004);the Hubei Provincial Natural Science Foundation(2021CFB453);the Science,Technology and Innovation Seed Fund of Zhongnan Hospital of Wuhan University(CXPY2020031);the Climbing Program for Medical Talents of Zhongnan Hospital of Wuhan University(PDJH202206,PDJH202208)。

摘　　要：Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain unclear.Consequently,elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies,ultimately advancing the management of PCa.Methods:A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan University.The advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in PCa.The expression of aspartoacylase(ASPA)in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting techniques.To elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis,a comprehensive set of in vitro and in vivo assays were conducted,including orthotopic and tumor-bearing mouse models(n=8 for each group).A combination of experimental approaches,such as Western blotting,luciferase assays,immunoprecipitation assays,mass spectrometry,glutathione S-transferase pulldown experiments,and rescue studies,were employed to investigate the underlying molecular mechanisms of ASPA's action in PCa.The Student‘s t-test was employed to assess the statistical significance between two distinct groups,while one-way analysis of variance was utilized for comparisons involving more than two groups.A two-sided P<0.05 was deemed to indicate statistical significance.Results:ASPA was identified as a novel inhibitor of PCa progression.The expression of ASPA was found to be significantly down-regulated in PCa tissue samples,and its decreased expression was independently associated with patients’prognosis(HR=0.60,95%CI 0.40–0.92,P=0.018).Our experiments demonstrated that modulation of ASPA activity,either through gain-or loss-of-function,led to the suppression or enhancement of PCa cell proliferation,migration,and invasion,respectively.The inhib

关 键 词：Prostate cancer Aspartoacylase LYN JNK AP-1 C-JUN PHOSPHORYLATION 

分 类 号：R737.25[医药卫生—肿瘤]