山西医科大学学报2025，Vol.56Issue(5)：524-533,10.DOI:10.13753/j.issn.1007-6611.2025.05.009
泛素特异性蛋白酶33在乳腺癌进展中的作用及其机制
Regulatory mechanism of ubiquitin-specific protease 33 in breast cancer progression
摘要
Abstract
Objective To investigate how USP33 regulates glycolytic metabolism and mediates molecular mechanisms in breast cancer cells.Methods The expression of USP33 in tumor tissues and paracancerous tissues of 32 patients with breast cancer was analyzed by RT-qPCR and Western blot.USP33 expression was assessed in normal breast epithelial cells(MCF-10A)and breast cancer cell lines(MDA-MB-23,SKBR3,BT-474,MCF-7)using RT-qPCR and Western blot.MCF-7 cells with the highest USP33 expression were selected for subsequent RNA interference experiments.These cells were divided into control group,si-NC group and si-USP33 group.MCF-7 cells were transfected with c-Myc overexpression vector and USP33 siRNA,respectively,named as control group,si-USP33 group,pcDNA3.1-c-Myc group and si-USP33+pcDNA3.1-c-Myc group.The proliferative,migratory,and invasive capacities of MCF-7 cells were assessed using CCK-8 assay,wound healing assay,and Transwell invasion assay,respectively.Lactic acid produc-tion,ATP content,and glucose uptake were quantitatively measured using kits.Glycolysis-related proteins GLUT1,PKM2,and c-Myc were detected by Western blot.Results USP33 expression was significantly upregulated at both mRNA and protein levels in breast cancer tissues relative to paracancerous tissues(P＜0.05).USP33 expression was significantly upregulated at both mRNA and protein levels in breast cancer cell lines(MDA-MB-231,SKBR3,BT-474,MCF-7)compared with normal mammary epithelial cells MCF-10A(P＜0.05).Compared with si-NC group,the proliferation,migration and invasion abilities of MCF-7 cells were decreased in si-USP33 group(P＜0.05).Compared with si-NC group,the levels of lactic acid and ATP in MCF-7 cells were significantly decreased in si-USP33 group(P＜0.05),the uptake of glucose was significantly decreased(P＜0.05),and the expression levels of glycoly sis-related proteins GLUT1 and PKM2 were significantly decreased(P＜0.05).Compared with si-NC group,the protein expression level of c-Myc was significantly decreased in si-USP33 group(P＜0.05).Compared with si-USP33 group,the expression levels of glycolytic pro-teins were significantly increased in si-USP33+pcDNA3.1-c-Myc group(P＜0.05).Conclusion Interference with USP33 inhibits the proliferation,migration and invasion of MCF-7 cells,and participates in the glycolysis process of breast cancer cells by regulating the expression of c-Myc,thus inhibiting the progression of breast cancer.关键词
乳腺癌/USP33/糖酵解/GLUT1/c-Myc/MCF-7细胞/细胞增殖/细胞迁移/细胞侵袭Key words
breast cancer/USP33/glycolysis/GLUT1/c-Myc/MCF-7 cells/cell proliferation/cell migration/cell invasion分类
医药卫生引用本文复制引用
王健岗,唐海利,赵华,师娇娇,姬国雄,杨小军,陈欣,杨小周..泛素特异性蛋白酶33在乳腺癌进展中的作用及其机制[J].山西医科大学学报,2025,56(5):524-533,10.基金项目
陕西省自然科学基础研究计划项目(2022JM-604) （2022JM-604）
