浙江大学学报（医学版）2026，Vol.55Issue(6)：528-539,12.DOI:10.3724/zdxbyxb-2025-0822
甲基转移酶样蛋白7B调控USP28/HIF-1α通路促进甲状腺乳头状癌细胞糖酵解及恶性进展
Methyltransferase-like protein 7B promotes glycolysis and malignant progression in papillary thyroid carcinoma cells via the USP28/HIF-1α axis
摘要
Abstract
Objective:To investigate the expression of methyltransferase-like protein 7B(METTL7B)in papillary thyroid carcinoma(PTC)and elucidate its role and molecular mechanisms in tumor metabolic reprogramming and malignant progression.Methods:Public datasets from Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)were used to analyze METTL7B expression in PTC and its association with clinicopathological features.Immunohistochemistry on tissue microarrays was performed to validate METTL7B protein expression in clinical samples.Stable METTL7B-knockdown PTC cell lines were constructed,and knockdown efficiency was confirmed by quantitative real-time PCR(qRT-PCR)and Western blotting.Cell proliferation and clonogenic potential were evaluated using MTT and colony formation assays.Transcrip-tome sequencing was conducted in METTL7B-overexpressing cells to identify differentially expressed genes and enriched pathways,followed by qRT-PCR and Western blotting validation of METTL7B-mediated regulation of hypoxia-inducible factor 1α(HIF-1α).Cycloheximide chase and ubiquitination assays were used to assess the effect of METTL7B on HIF-1α protein stability,and the involvement of ubiquitin-specific protease 28(USP28)was further examined.Lactate production and glucose uptake assays were performed to assess the impact of METTL7B and HIF-1α on glycolytic activity.Results:METTL7B was significantly upregulated in PTC tissues(P<0.05)and positively correlated with lymph node metastasis(P<0.05).METTL7B knockdown markedly suppressed PTC cell proliferation and colony formation(all P<0.05),and markedly reduced the growth rate of PTC xenograft tumors in nude mice,with tumor volumes smaller than those in the control group(P<0.05).Bioinformatics analysis suggested a strong association between METTL7B and the HIF-1α signaling pathway.METTL7B knockdown reduced HIF-1α protein levels without affecting its mRNA expression.Mechanistically,METTL7B inhibited the ubiquitination and degradation of HIF-1α,thereby maintaining its protein stability,and this process was mediated by USP28.Functional assays demonstrated that METTL7B enhanced glycolytic activity and malignant phenotypes of PTC cells by upregulating glycolysis-related genes through the USP28/HIF-1α axis.Conclusion:METTL7B promotes glycolysis and malignant progression in PTC cells by stabilizing HIF-1α through USP28-mediated deubiquitination.关键词
甲状腺乳头状癌/甲基转移酶样蛋白7B/低氧诱导因子1α/泛素特异性蛋白酶28/糖酵解/裸鼠Key words
Papillary thyroid carcinoma/Methyltransferase-like protein 7B/Hypoxia-inducible factor-1α/Ubiquitin-specific protease 28/Glycolysis/Nude mice分类
医药卫生引用本文复制引用
徐逢雨,谢秋萍..甲基转移酶样蛋白7B调控USP28/HIF-1α通路促进甲状腺乳头状癌细胞糖酵解及恶性进展[J].浙江大学学报（医学版）,2026,55(6):528-539,12.基金项目
国家自然科学基金(82303597)The study was supported by National Natural Science Foundation of China(82303597) （82303597）
