中山大学学报(医学科学版)2026,Vol.47Issue(4):670-680,11.DOI:10.11714/jsysu.med.YX20260051
CYHR1通过激活IL-6/STAT3/MALAT1轴调控结直肠癌细胞的增殖与迁移侵袭
CYHR1 Regulates the Proliferation,Migration,and Invasion of Colorectal Cancer Cells by Activating the IL-6/STAT3/MALAT1 Axis
摘要
Abstract
[Objective]To elucidate the expression patterns of CYHR1 in colorectal cancer(CRC)and its regulatory role in tumour cell proliferation and metastasis-related phenotypes.[Methods]Expression differences of CYHR1 between colorectal cancer tissues and adjacent normal tissues were analyzed using data from The Cancer Genome Atlas(TCGA)database,and the association between CYHR1 expression and patient survival was evaluated.A CRC cell model with CYHR1 overexpression was established,and changes in the expression of related molecules were verified by quantitative real-time PCR(qRT-PCR).Cell proliferation and metastatic potential were assessed using MTT assays,colony formation assays,and Transwell migration and invasion assays to evaluate the effects of CYHR1 and MALAT1 on CRC cell proliferation and migration/invasion,including combined intervention experiments.[Results]Database analysis revealed that CYHR1 is significantly overexpressed in CRC tissues,and that this overexpression is significantly associated with poorer overall survival.Compared with normal control cells,mRNA expression levels of CYHR1 were markedly elevated in CRC cell lines(HCT116,RKO,etc.)(P=0.002;P=0.006).Functional experiments demonstrated that CYHR1 overexpression significantly promoted the proliferation(P<0.001),colony formation(P<0.001),migration(P=0.002)and invasive capacity(P=0.002)of HCT116 cells;whereas knockdown of either CYHR1 or MALAT1 inhibited CRC cell proliferation and reduced their migration(P=0.006)and invasive capacity(P=0.006).In the context of CYHR1 overexpression,combined knockdown of MALAT1 partially reversed the promotional effect of CYHR1 on CRC cell proliferation,migration and invasion(P<0.001;P=0.001).Mechanistic studies further revealed that CYHR1 overexpression upregulates MALAT1 mRNA expression levels(P<0.001),whilst CYHR1 knockdown leads to downregulation of MALAT1 expression(P<0.001);MALAT1 knockdown likewise downregulates CYHR1 expression,suggesting a mutually reinforcing positive regulatory relationship between the two.Furthermore,CYHR1 can activate the IL-6/STAT3 signalling axis,whilst knockdown of IL-6 or STAT3 inhibited the upregulation of MALAT1 expression by CYHR1(P=0.031;P=0.006).[Conclusion]CYHR1 is abnormally overexpressed in colorectal cancer and is closely associated with poor prognosis.CYHR1 may promote the proliferation,migration,and invasion of colorectal cancer(CRC)cells by activating the IL-6/STAT3/MALAT1 axis.关键词
结直肠癌/半胱氨酸/组氨酸蛋白1/肺腺癌转移相关转录本1/增殖/迁移/侵袭Key words
colorectal cancer/cysteine/histidine-rich 1/metastasis-associated lung adenocarcinoma transcript 1/proliferation/migration/invasion分类
医药卫生引用本文复制引用
邓秋敏,刘莹,黄嘉颖,刘小会,高学娟,刘朗夏..CYHR1通过激活IL-6/STAT3/MALAT1轴调控结直肠癌细胞的增殖与迁移侵袭[J].中山大学学报(医学科学版),2026,47(4):670-680,11.基金项目
国家自然科学基金(32370966) (32370966)
广东省基础与应用基础研究基金(2025A1515012769) (2025A1515012769)
肿瘤分子生物学教育部重点实验室开放课题(202402) (202402)