Silencing of matrix metalloprotease-12 delays the progression of castration-resistant prostate cancer by regulating autophagy and lipolysis

作者全名："Zheng, Xiaoyu; Xie, Xiaoqin; Wang, Wei; Wang, Liang; Tan, Bing"

作者地址："[Zheng, Xiaoyu; Tan, Bing] Chongqing Med & Pharmaceut Coll, Sch Clin Med, Chongqing, Peoples R China; [Xie, Xiaoqin] Chongqing Blood Ctr, Dept Clin Lab, Chongqing, Peoples R China; [Wang, Wei] Peoples Hosp Yubei Dist Chongqing City, Dept Orthoped, Chongqing, Peoples R China; [Wang, Liang] Army Med Univ, Daping Hosp, Dept Dermatol, Chongqing, Peoples R China; [Tan, Bing] Chongqing Med Univ, Univ Town Hosp, Dept Urol, Chongqing, Peoples R China; [Tan, Bing] Chongqing Med Univ, Univ Town Hosp, Med Sci Res Ctr, Chongqing, Peoples R China"

通信作者："Tan, B (通讯作者)，Chongqing Med & Pharmaceut Coll, Sch Clin Med, Chongqing, Peoples R China.; Tan, B (通讯作者)，Chongqing Med Univ, Univ Town Hosp, Dept Urol, Chongqing, Peoples R China.; Tan, B (通讯作者)，Chongqing Med Univ, Univ Town Hosp, Med Sci Res Ctr, Chongqing, Peoples R China."

来源：BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001188324000001

JCR分区：Q2

影响因子：1.9

年份：2024

卷号：57

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：CRPC; MMP-12 Autophagy; Lipolysis

摘要："The complex pathogenesis of castration-resistant prostate cancer (CRPC) makes it challenging to identify effective treatment methods. Matrix metalloproteinase (MMP)-12 can degrade elastin as well as various extracellular matrix (ECM) components, which is associated with cancer progression. However, the relationship between MMP-12 and CRPC progression is poorly understood. In this study, we observed the effect of MMP-12 on the progression of CRPC and further explored its potential mechanism of action. High levels of MMP-12 were observed in patients with CRPC. We therefore developed cell co-culture and mouse models to study the function of MMP-12. Silencing MMP-12 in CRPC cells disrupted lipid utilization and autophagy marker expression via the CD36/CPT1 and P62/LC3 pathways, respectively, leading to reduced CRPC cell migration and invasion. Moreover, animal experiments confirmed that MMP-12-knockdown CRPC xenograft tumors exhibited reduced tumor growth, and the mechanisms involved the promotion of cancer cell autophagy and the inhibition of lipid catabolism. According to our results, MMP-12 played important roles in the progression of CRPC by disrupting adipocyte maturation and regulating cancer migration and invasion via the modulation of autophagy and lipid catabolism pathways."

基金机构："Natural Science Foundation of Chongqing, China [cstc2021jcyj-msxmX0704]; China Postdoctoral Science Foundation [2022MD723740]; Natural Science Foundation of Chongqing Medical and Pharmaceutical College [ygz2020301]"

基金资助正文："The authors acknowledge the following support: Natural Science Foundation of Chongqing, China (Num- ber: cstc2021jcyj-msxmX0704) , China Postdoctoral Science Foundation (Number: 2022MD723740) , and Natural Science Foundation of Chongqing Medical and Pharmaceutical College (Number: ygz2020301) ."