miR-30a-5p通过调控CTHRC1抑制甲状腺未分化癌进展OA
miR-30a-5p inhibits the progression of anaplastic thyroid carcinoma by regulating CTHRC1
目的:探讨三螺旋重复胶原蛋白1(collagen triple helix repeat containing-1,CTHRC1)在甲状腺癌中的表达与患者预后和免疫细胞浸润的关系,并进一步探讨CTHRC1对甲状腺癌未分化癌(anaplastic thyroid cancer,ATC)细胞体外增殖、迁移、侵袭和凋亡的影响,及miR-30a-5p在其中发挥的作用.方法:基于癌症基因组图谱(The Cancer Genome At-las,TCGA)和基因表达综合数据库(Gene Expression Omnibus,GEO)分析CTHRC1在甲状腺癌组织中的表达及其与患者生存、临床病理特征和免疫细胞浸润的关系.通过RT-qPCR和Western blot检测CTHRC1 mRNA和蛋白表达.通过CCK8、Transwell和流式细胞术检测ATC细胞增殖、迁移、侵袭和凋亡.通过ENCORI数据库筛选CTHRC1的上游调控因子miR-30a-5p,并分析二者在甲状腺癌中的表达相关性.通过RT-qPCR检测过表达miR-30a-5p对ATC细胞CTHRC1 mRNA表达的影响,双荧光素酶报告基因实验验证二者结合.结果:TCGA数据库分析显示CTHRC1 mRNA在甲状腺癌组织中表达上调,且与患者不良预后有关.免疫浸润分析提示,CTHRC1的表达在甲状腺癌中与多种免疫细胞群有关,包括T细胞、B细胞、细胞毒性细胞、NK细胞和树突状细胞等.GEO数据库分析显示CTHRC1在ATC组织中表达上调,RT-qPCR提示CTHRC1 mRNA在多株ATC细胞中表达上调.敲减CTHRC1可以抑制ATC细胞增殖、迁移和侵袭,促进凋亡.CTHRC1与miR-30a-5p结合,过表达miR-30a-5p可以降低ATC细胞中CTHRC1 mRNA表达,miR-30a-5p和CTHRC1的表达在甲状腺癌中呈显著负相关.抑制miR-30a-5p逆转了敲减CTHRC1对ATC细胞体外增殖、迁移和侵袭的抑制,以及凋亡的促进.结论:CTHRC1可能是ATC重要的预后生物标志物,miR-30a-5p通过调控CTHRC1表达抑制ATC细胞恶性生物学行为.
Objective:To investigate the relationship of the expression of collagen triple helix repeat containing-1(CTHRC1)in thyroid cancer with patient prognosis and immune cell infiltration,and to further explore the effect of CTHRC1 on the proliferation,migration,invasion and apoptosis of anaplastic thyroid carcinoma(ATC)cells in vitro and the role of miR-30a-5p in this process.Methods:The expression of CTHRC1 in thyroid carcinoma and its relationship with survival,clinicopathological features and immune cell infiltration were analyzed based on The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO).RT-qPCR and Western blot were used to detect CTHRC1 mRNA and protein expression.CCK-8,Transwell assays,and flow cytometry were employed to detect the proliferation,migration,invasion,and apoptosis of ATC cells.The ENCORI database was used to screen for the upstream regulator of CTHRC1,miR-30a-5p,and the expression correlation between them in thyroid cancer was analyzed.RT-qPCR was used to detect the effect of miR-30a-5p overexpression on CTHRC1 mRNA expression in ATC cells,and a dual-luciferase reporter gene assay was performed to validate their binding.Results:TCGA database analysis showed that the expression of CTHRC1 mRNA was up-regulated in thyroid carcinoma and was related to poor prognosis.Immune infiltration analysis showed that CTHRC1 expression in thyroid carcinoma was related to various immune cell populations,including T cells,B cells,cytotoxic cells,NK cells and dendritic cells.GEO database analysis showed that the expression of CTHRC1 was up-regulated in ATC tissues,and RT-qPCR confirmed that CTHRC1 mRNA was up-regulated in several ATC cells.Knockdown of CTHRC1 inhibited the proliferation,migration and invasion of ATC cells and promotd apoptosis.The dual-luciferase reporter gene assay verified the combination of CTHRC1 and miR-30a-5p.Overexpression of miR-30a-5p reduced the expression of CTHRC1 mRNA in ATC cells.The expression of miR-30a-5p and CTHRC1 showed a significant negative correlation in thyroid cancer.Inhibition of miR-30a-5p reversed the suppressive effect of CTHRC1 knockdown on the proliferation,migration and invasion of ATC cells,as well as the promotion of apoptosis.Conclusion:CTHRC1 may be an important prognostic biomarker for ATC,and miR-30a-5p inhibits the malignant biological behavior of ATC cells by regulating CTHRC1.
陈晶晶;俞建华;张凤霞;孙成林;康永生
郑州市骨科医院医保科,河南 郑州 450052郑州市第一人民医院普外科郑州市骨科医院医保科,河南 郑州 450052沈阳医学院附属中心医院普外科郑州市骨科医院医保科,河南 郑州 450052
医药卫生
甲状腺未分化癌CTHRC1miR-30a-5p细胞迁移和侵袭细胞凋亡
anaplastic thyroid carcinomaCTHRC1miR-30a-5pcell migration and invasioncell apoptosis
《沈阳医学院学报》 2026 (1)
30-37,8
辽宁省科学技术计划重大科研项目(No.2022JH2/101300035)沈阳市科学技术计划项目基金(No.21-173-9-18)
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