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ZC3H13通过Ras-ERK信号通路抑制甲状腺癌发生发展

ZC3H13 inhibits the occurrence and development of thyroid cancer through the Ras-ERK signaling pathway
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摘要 [目的]探究CCCH型锌指蛋白13(ZC3H13)在甲状腺癌(TC)发生发展的作用及可能机制。[方法]收集57例TC组织和对应癌旁组织、TC细胞(TPC-1,KTC-1,WRO)和正常甲状腺细胞Nthy-ori 3-1,Western Blot检测各组织、细胞中ZC3H13蛋白表达。选择TPC-1细胞随机分为control组、ZC3H13组(过表达ZC3H13)和NC组,CCK-8、Transwell、划痕实验检测各组细胞增殖、侵袭、转移水平,Western Blot检测Ras、细胞外信号调节激酶(ERK)、Snail、金属基质蛋白酶2(MMP-2)、胞质紧密黏连蛋白1(Zo-1)蛋白表达。[结果]TPC-1细胞TC组织ZC3H13蛋白表达低于癌旁组织(0.17±0.02 vs 0.99±0.01),TPC-1、KTC-1、WRO细胞ZC3H13蛋白表达低于Nthy-ori 3-1细胞(P<0.05);Western Blot检测ZC3H13组细胞ZC3H13蛋白表达高于control组和NC组(1.73±0.11 vs 1.05±0.18,1.11±0.23,P<0.05);ZC3H13组细胞增殖水平(0.91±0.11 vs 1.46±0.13,1.52±0.14)、侵袭数(74.64±12.18 vs 105.31±15.72,108.74±16.34)个、迁移率(19.42±2.13 vs 54.27±7.32,51.81±9.31)%均低于control组和NC组(P<0.05);与control组和NC组比较,ZC3H13组细胞MMP-2、Zo-1蛋白表达升高,K-Ras、p-ERK、Snail蛋白表达降低(P<0.05)。[结论]ZC3H13在TC组织及细胞中低表达,上调ZC3H13表达可抑制TPC-1细胞增殖、侵袭、转移能力,这可能是通过抑制Ras-ERK信号通路(0.65±0.12 vs 0.35±0.16)实现的。 [Objective]To explore the role and possible mechanism of zinc finger CCCH domain-containing protein 13(ZC3H13)in the occurrence and development of thyroid cancer(TC).[Method]Fifty-seven matched pairs of TC tissues and adjacent normal tissues,TC cell lines(TPC-1,KTC-1,WRO),and human thyroid follicular epithelial cell line Nthy-ori 3-1 were collected.The expression of ZC3H13 in tissues and cells was measured using Western Blot assay.TPC-1 cells were randomly assigned into control group,ZC3H13 group(overexpression of ZC3H13)and NC group.TPC-1 cell proliferation,invasion and metastatic ability in each group were detected by CCK-8 assay,Transwell chamber and scratch test,and the protein expression of Ras,extracellular signal-regulated kinase(ERK),Snail,matrix metalloproteinase 2(MMP-2),and tight junction protein 1(Zo-1)was detected by Western Blot.[Result]The ZC3H13 protein expression in TC tissues of TPC-1 cells was lower than that in adjacent normal tissues(0.17±0.02 vs 0.99±0.01),and the ZC3H13 protein expression was decreased in TPC-1,KTC-1 and WRO cells compared with Nthy-ori-3-1 cells,with statistical difference(all P<0.05).Western Blot analysis showed that the expression level of ZC3H13 protein in ZC3H13 group cells was higher than that in control group and NC group(1.73±0.11 vs 1.05±0.18,1.11±0.23,P<0.05).The cell proliferation,invasion number and migration rate were(0.91±0.11),(74.64±12.18)and(19.42±2.13)%in ZC3H13 group,which were all lower than(1.46±0.13),(105.31±15.72)and(54.27±7.32)%in control group,and(1.52±0.14),(108.74±16.34)and(51.81±9.31)%in NC group,with statistical difference(all P<0.05).Compared with control group and NC group,protein expression of MMP-2 and Zo-1 was upregulated and protein expression of K-Ras,p-ERK and Snail was downregulated in ZC3H13 group,with statistical difference(all P<0.05).[Conclusion]ZC3H13 expression is down-regulated in TC tissues and cells,and the up-regulation of ZC3H13 expression can inhibit the proliferation,invasion,and metastatic ability of TPC-1 cells,which may be related to the inhibition of Ras-ERK signaling pathway(0.65±0.12 vs 0.35±0.16).
作者 于景超 魏雅楠 李卫 鲁金乐 陈雅婷 王猛 潘磊 庞燕 李研 刘杰 YU Jingchao;WEI Ya′nan;LI Wei;LU Jinle;CHEN Yating;WANG Meng;PAN Lei;PANG Yan;LI Yan;LIU Jie(Department of Head and Neck Thyroid Surgery,Cangzhou Hospital of Integrated TCM-WM,Cangzhou 061000,China;Department of Traditional Chinese Medicine,Cangzhou Hospital of Integrated TCM-WM,Cangzhou 061000,China;Department of Infectious Diseases,Cangzhou Hospital of Integrated TCM-WM,Cangzhou 061000,China;Department of Radiotherapy,East Area of Cangzhou Hospital of Integrated TCM-WM,Cangzhou 061000,China;Department of 2th Surgery,East Area of Cangzhou Hospital of Integrated TCM-WM,Cangzhou 061000,China)
出处 《生物技术》 2025年第1期68-73,共6页 Biotechnology
基金 河北省中医药管理局科研计划项目(2020474)。
关键词 CCCH型锌指蛋白13 甲状腺癌 Ras-ERK 增殖 侵袭 转移 SNAIL 金属基质蛋白酶2 胞质紧密粘连蛋白1 zinc finger CCCH domain-containing protein 13 thyroid cancer Ras-ERK proliferation invasion metasta-sis Snail matrix metalloproteinase 2 tight junction protein 1
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