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OA
CYHR1 Regulates the Proliferation,Migration,and Invasion of Colorectal Cancer Cells by Activating the IL-6/STAT3/MALAT1 Axis
[目的]阐明CYHR1在CRC中的表达特征及其对肿瘤细胞增殖和转移相关表型的调控作用.[方法]基于TCGA数据库分析CYHR1在结直肠癌组织与癌旁组织中的表达差异,并评估其与患者生存预后的相关性.构建CYHR1过表达的CRC细胞模型,采用qRT-PCR验证相关分子的表达变化;通过MTT实验、克隆形成实验以及Transwell迁移和侵袭实验,评估 CYHR1与MALAT1对CRC细胞增殖及转移能力的影响,并进一步开展联合干预实验.[结果]数据库分析结果显示,CYHR1在CRC组织中显著高表达,且其高表达与较差的总体生存期显著相关.与正常对照细胞相比,CRC细胞系(HCT116、RKO等)中CYHR1的mRNA表达水平明显升高(P=0.002;P=0.006).功能实验表明,CYHR1过表达可显著促进HCT116细胞的增殖(P＜0.001)、克隆形成(P＜0.001)以及迁移(P=0.002)和侵袭能力(P=0.002);而敲低CYHR1或MALAT1均可抑制CRC细胞增殖并降低其迁移(P=0.006)和侵袭能力(P=0.006).在CYHR1过表达的背景下联合敲低MALAT1,可部分逆转CYHR1对CRC细胞增殖及迁移侵袭的促进作用(P＜0.001;P=0.001).机制研究进一步发现,CYHR1过表达可上调MALAT1的mRNA表达水平(P＜0.001),而敲低CYHR1则导致MALAT1表达下调(P＜0.001);敲低MALAT1同样可下调CYHR1的表达,提示二者之间可能存在相互促进的正向调控关系.此外,CYHR1可以激活IL-6/STAT3信号轴,而敲低IL-6或STAT3则抑制了CYHR1对MALAT1(P=0.031;P=0.006)表达的上调作用.[结论]CYHR1在结直肠癌中异常高表达并与不良预后密切相关.CYHR1可能通过激活IL-6/STAT3/MALAT1轴促进CRC细胞的增殖、迁移和侵袭.
[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.
邓秋敏;刘莹;黄嘉颖;刘小会;高学娟;刘朗夏
暨南大学肿瘤分子生物学教育部重点实验室//暨南大学生命科学技术学院,广东 广州 510632暨南大学肿瘤分子生物学教育部重点实验室//暨南大学生命科学技术学院,广东 广州 510632暨南大学肿瘤分子生物学教育部重点实验室//暨南大学生命科学技术学院,广东 广州 510632暨南大学肿瘤分子生物学教育部重点实验室//暨南大学生命科学技术学院,广东 广州 510632暨南大学肿瘤分子生物学教育部重点实验室//暨南大学生命科学技术学院,广东 广州 510632暨南大学肿瘤分子生物学教育部重点实验室//暨南大学生命科学技术学院,广东 广州 510632
医药卫生
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
colorectal cancercysteine/histidine-rich 1metastasis-associated lung adenocarcinoma transcript 1proliferationmigrationinvasion
《中山大学学报（医学科学版）》 2026 (4)
670-680,11
国家自然科学基金(32370966)广东省基础与应用基础研究基金(2025A1515012769)肿瘤分子生物学教育部重点实验室开放课题(202402)
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