中国肿瘤生物治疗杂志2025,Vol.32Issue(10):1019-1026,8.DOI:10.3872/j.issn.1007-385x.2025.10.003
HMMR通过介导FAM83D促进4NQO诱导的食管鳞状细胞癌的进展
HMMR promotes the progression of 4NQO-induced esophageal squamous cell carcinoma by mediating FAM83D
摘要
Abstract
Objective:To investigate the role of hyaluronic acid-mediated motion receptor(HMMR)in the malignant progression of esophageal squamous cell carcinoma(ESCC)cells and its potential molecular mechanisms.Methods:8 samples of ESCC tissues and adjacent paracancerous tissues surgically removed at the Fourth Hospital of Hebei Medical University between January 2018 and December 2020,as well as ESCC cells KYSE-30 and KYSE-150,were collected.Western blotting(WB)and immunohistochemistry(IHC)were used to detect the expression of HMMR in ESCC tissues.RNA interference was used to knock down HMMR expression in KYSE-30 and KYSE-150 cells,and qPCR and WB were used to detect the knockdown effect.The effects of HMMR knockdown on the proliferation and invasion abilities of ESCC cells were detected by CCK-8 assay and Transwell assay,respectively.4-nitroquinoline 1-oxide(4NQO)was used to induce carcinogenesis in mice and establish an ESCC model.H-E staining was used to observe the morphological changes of esophagus,and IHC was used to analyze the expressions of HMMR,FAM83D(family with sequence similarity 83 member D),E-cadherin and N-cadherin in tissues of different degrees of carcinogenesis in mice.Results:The expression level of HMMR in human ESCC tissues was significantly higher than that in adjacent paracancerous tissues(all P<0.05).After HMMR knockdown,the proliferation and invasion abilities of KYSE-30 and KYSE-150 cells were significantly reduced(P<0.05 or P<0.01),and the expression level of FAM83D also decreased(all P<0.01).In nude mouse tumor experiment,the body weight of mice in the 4NQO group was lower than that of the control group(all P<0.05).The results of IHC staining showed that HMMR was highly expressed in tumor tissues(P<0.05),and the expression of HMMR in high-grade intraepithelial neoplasia(HGIN)tissues was significantly higher than that in low-grade intraepithelial neoplasia(LGIN)tissues(P<0.001).HMMR was positively correlated with the expressions of FAM83D and N-cadherin(r=0.724,0.870,all P<0.001),and negatively correlated with the expression of E-cadherin(r=-0.714,P<0.001).Conclusion:HMMR is highly expressed in ESCC tissues and may promote the progression of ESCC by up-regulating FAM83D expression.关键词
透明质酸介导运动受体/4-硝基喹啉1-氧化物/序列相似性家族83成员D/食管鳞状细胞癌/上皮间质转化Key words
hyaluronan mediated motility receptor(HMMR)/4-nitroquinoline l-oxide(4NQO)/family with sequence similarity 83 member D(FAM83D)/esophageal squamous cell carcinoma(ESCC)/epithelial-mesenchymal transition(EMT)分类
医药卫生引用本文复制引用
田建兵,秦芷若,李锦锦,刘开了,杨兴肖..HMMR通过介导FAM83D促进4NQO诱导的食管鳞状细胞癌的进展[J].中国肿瘤生物治疗杂志,2025,32(10):1019-1026,8.基金项目
国家自然科学基金(No.81903118) (No.81903118)
河北省医学科学研究课题计划资助项目(No.20180483,No.20240092) (No.20180483,No.20240092)