Zhou Ting, Li Xiaorong, Zhao Fangfang, Zhou Jing, Sun Binghui
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Laboratory of Laparoscopic Technology, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, Shandong, China.
Department of Obstetrics and Gynecology, Weihaiwei People's Hospital, Weihai, 264299, Shandong, China.
Arch Biochem Biophys. 2025 Feb;764:110287. doi: 10.1016/j.abb.2024.110287. Epub 2024 Dec 31.
Lactamase β (LACTB) inhibits the metastasis and progression of multiple malignant tumors. However, little is known about its role in endometrial cancer (EC). Our study aimed to investigate the function and potential molecular mechanism of LACTB in modulating EC progression.
LACTB expression was measured via immunohistochemistry staining, Western blot and qRT-PCR. The role of LACTB in EC was investigated both in vivo and in vitro by employing xenograft mice models and using colony formation, EdU, and Transwell assays, along with flow cytometric analysis. In addition, to assess LACTB function on lipid metabolism, lipid droplets in EC cells were labeled with Nile red. Western blot, immunofluorescence staining, co-immunoprecipitation, ubiquitination assay, and cycloheximide chase assay and rescue experiments were performed to confirm the interaction between LACTB, p53, and MDM2 in EC.
LACTB expression was downregulated in EC. LACTB inhibited the malignant phenotypes and reprogramed lipid metabolism in EC cells. Moreover, LACTB significantly upregulated p53 by attenuating the MDM2-mediated ubiquitination and degradation of p53. Besides, LACTB silencing facilitated the malignant phenotypes and reprogramed lipid metabolism in EC cells; this was reversed with p53 overexpression. LACTB knockdown facilitated EC progression via downregulating p53 in vivo.
LACTB repressed EC cell proliferation and metastasis, and reprogramed lipid metabolism via attenuating the MDM2-mediated ubiquitination and degradation of p53.
β-内酰胺酶（LACTB）可抑制多种恶性肿瘤的转移和进展。然而，其在子宫内膜癌（EC）中的作用鲜为人知。我们的研究旨在探讨LACTB在调节EC进展中的功能及潜在分子机制。
通过免疫组织化学染色、蛋白质印迹法和qRT-PCR检测LACTB表达。采用异种移植小鼠模型以及集落形成、EdU和Transwell实验，并结合流式细胞术分析，在体内和体外研究LACTB在EC中的作用。此外，为评估LACTB对脂质代谢的功能，用尼罗红标记EC细胞中的脂滴。进行蛋白质印迹法、免疫荧光染色、免疫共沉淀、泛素化实验、放线菌酮追踪实验和挽救实验，以证实EC中LACTB、p53和MDM2之间的相互作用。
EC中LACTB表达下调。LACTB抑制EC细胞的恶性表型并重塑脂质代谢。此外，LACTB通过减弱MDM2介导的p53泛素化和降解显著上调p53。此外，LACTB沉默促进了EC细胞的恶性表型并重塑脂质代谢；p53过表达可逆转这种情况。在体内，LACTB敲低通过下调p53促进EC进展。
LACTB通过减弱MDM2介导的p53泛素化和降解来抑制EC细胞增殖和转移，并重塑脂质代谢。
