敲低S100A1通过降低WNT/β-catenin信号活性抑制甲状腺癌SW579细胞增殖

doi:10.3969/j.issn.1671-2587.2021.02.003

临床输血与检验 ›› 2021, Vol. 23 ›› Issue (2): 146-152.DOI: 10.3969/j.issn.1671-2587.2021.02.003

敲低S100A1通过降低WNT/β-catenin信号活性抑制甲状腺癌SW579细胞增殖

郑艳, 张茜, 孙菲

100050 首都医科大学附属北京友谊医院临床检验中心

收稿日期:2020-09-23 出版日期:2021-04-20 发布日期:2021-04-19
通讯作者: 孙菲,女,研究生,检验师,主要从事临床检验诊断学方面研究, （E-mail）hbzjk2019@126.com。
作者简介:郑艳（1986-）,女,本科,检验师,主要从事临床检验诊断学方面研究,（E-mail）xiaofudi3626@163.com。

Down-Regulation of S100A1 Negatively Regulates Wnt/β- catenin Signaling Activity and Inhibits Proliferation of Thyroid Cancer SW579 Cells

ZHENG Yan, ZHANG Qian, SUN Fei

Clinical Laboratory Center of Beijing Friendship Hospital, Capital Medical University, Beijing 100050

Received:2020-09-23 Online:2021-04-20 Published:2021-04-19

摘要/Abstract

摘要： 目的探究钙结合蛋白S100A1对人甲状腺癌SW579细胞增殖的影响及其作用机制。方法选取人甲状腺癌数据集GSE50901和GSE138198,使用R软件筛选甲状腺癌组织与正常甲状腺组织中的差异表达基因,联合TCGA数据库对差异表达基因进行验证;采用CCK-8实验检测S100A1敲低或过表达对人甲状腺癌SW579细胞增殖的影响;Western Blot检测S100A1敲低或者过表达对WNT/β-catenin信号通路的影响。结果对数据集GSE50901和GSE138198进行联合分析发现,有97个基因在两个数据集中均发生上调,46个基因均发生下调。S100A1基因在甲状腺癌中高表达,敲低S100A1能抑制SW579细胞的增殖,过表达S100A1则能促进SW579细胞的增殖。GSEA分析发现,敲低SW579细胞的S100A1后,WNT信号显著富集,且表现为信号通路活性降低。Western Blot结果表明,敲低S100A1的SW579细胞中β-catenin,c-myc和cyclinD1的蛋白表达水平明显低于对照组,而过表达S100A1的SW579细胞中β-catenin,c-myc和cyclinD1的蛋白表达水平则显著高于对照组。结论 S100A1在甲状腺癌中高表达,敲低S100A1可能是通过抑制WNT/β-catenin信号通路活性从而抑制甲状腺癌SW579细胞增殖。

关键词: S100A1, 生物信息学, 甲状腺癌, WNT/β-catenin信号通路

Abstract: Objective To explore the effect of S100A1 on the proliferation of human thyroid cancer SW579 cells and its mechanism. Methods The human thyroid cancer data sets GSE50901 and GSE138198 were selected, and R software was used to screen the differentially expressed genes in thyroid cancer tissues and normal thyroid tissues. The differentially expressed genes were verified with TGCA database. CCK-8 experiment was used to detect the effect of S100A1 knockdown or overexpression on the proliferation of human thyroid cancer SW579 cell. Western Blot was used to detect the effect of S100A1 on the WNT/β-catenin signaling pathway. Results A joint analysis of the data sets GSE50901 and GSE138198 showed that 97 genes were up-regulated in both data sets, and 46 genes were down-regulated. S100A1 gene is highly expressed in thyroid cancer. Knockdown of S100A1 could inhibit the proliferation of SW579 cells, and overexpression of S100A1 could promote the proliferation of SW579 cells. GSEA analysis found that WNT signal pathway was significantly enriched after knocking down S100A1 in SW579 cells, and the signal pathway activity was reduced. Western Blot results showed that the protein expression levels of β-catenin, c-myc and cyclin D1 in the siS100A1 group were significantly lower than those in the siNeg group, while the protein expression levels of β-catenin, c-myc and cyclin D1 in the S100A1 group were significant higher than those in the EGFP group. Conclusion S100A1 is highly expressed in thyroid cancer. Knockdown of S100A1 might inhibit the proliferation of thyroid cancer SW579 cells by inhibiting the activity of WNT/β-catenin signaling pathway.

Key words: S100A1, Bioinformatics, Thyroid cancer, WNT/β-catenin signaling pathway

中图分类号:

R736.1

郑艳, 张茜, 孙菲. 敲低S100A1通过降低WNT/β-catenin信号活性抑制甲状腺癌SW579细胞增殖[J]. 临床输血与检验, 2021, 23(2): 146-152.

ZHENG Yan, ZHANG Qian, SUN Fei. Down-Regulation of S100A1 Negatively Regulates Wnt/β- catenin Signaling Activity and Inhibits Proliferation of Thyroid Cancer SW579 Cells[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2021, 23(2): 146-152.

参考文献

[1] 翟健,胡万宁,李军,等.P21基因过表达对甲状腺癌细胞增殖和凋亡的影响及其作用机制[J].癌症进展,2019,17(3):280-283.
[2] PITOIA F,SMULEVER A.Active surveillance in low risk papillary thyroid carcinoma[J].World J Clin Oncol,2020,11(6):320-336.
[3] HAROON AL RASHEED M R,XU B.Molecular alterations in thyroid carcinoma[J].Surg Pathol Clin,2019,12(4):921-930.
[4] CABANILLAS M E,RYDER M,JIMENEZ C.Targeted therapy for advanced thyroid cancer: kinase inhibitors and beyond[J].Endocr Rev,2019,40(6):1573-1604.
[5] HUANG J,HARRIS E J,LORCH J H.Treatment of aggressive thyroid cancer[J].Surg Pathol Clin,2019,12(4):943-950.
[6] BERDELOU A,LAMARTINA L,KLAIN M,et al.Treatment of refractory thyroid cancer[J].Endocr - Relat Cancer,2018,25(4):R209-R223.
[7] DIAZ-ROMERO J,NESIC D.S100A1 and S100B: calcium sensors at the cross-roads of multiple chondrogenic pathways[J].J Cell Physiol,2017,232(8):1979-1987.
[8] MELVILLE Z,ALIGHOLIZADEH E,MCKNIGHT L E,et al.X-ray crystal structure of human calcium-bound S100A1[J].Acta Crystallogr F Struct Biol Commun,2017,73(Pt 4):215-221.
[7] GUO Y C,CUI L Q,JIANG S L,et al.S100A1 transgenic treatment of acute heart failure causes proteomic changes in rats[J].Mol Med Rep,2016,14(2):1538-1552.
[10] SCOTT C E,KEKENES-HUSKEY P M.Molecular basis of S100A1 activation at saturating and subsaturating calcium concentrations[J].Biophys J,2016,110(8): 1907.
[11] NUCCI N V.New insight on the S100A1-STIP1 complex highlights the important relationship between allostery and entropy in protein function[J].Biochem J,2017,474(17):2977-2980.
[12] XIONG T F,PAN F Q,LI D.Expression and clinical significance of S100 family genes in patients with melanoma[J].Melanoma Res,2019,29(1):23-29.
[13] NUSAIR S D,JOUKHAN A N,RASHAID A B,et al.Methomyl induced effect on fortilin and S100A1 in serum and cardiac tissue: Potential biomarkers of toxicity[J].Hum Exp Toxicol,2019,38(3):371-377.
[14] GUO Q P,WANG J L,CAO Z Y,et al.Interaction of S100A1 with LATS1 promotes cell growth through regulation of the Hippo pathway in hepatocellular carcinoma[J].Int J Oncol,2018,53(2):592-602.
[15] TIAN T,LI X K,HUA Z,et al.S100A1 promotes cell proliferation and migration and is associated with lymph node metastasis in ovarian cancer[J].Discov Med,2017,23(127):235-245.
[16] NUSSE R,CLEVERS H.Wnt/β-catenin signaling,disease,and emerging therapeutic modalities[J].Cell,2017,169(6):985-999.
[17] ZHAN T,RINDTORFF N,BOUTROS M.Wnt signaling in cancer[J].Oncogene,2017,36(11):1461-1473.
[18] 邵宇鑫,陶雅军,汪轩羽,等.分化型甲状腺癌中β-catenin和VDR的表达及意义[J].临床与实验病理学杂志,2019,35(9):1105-1107.
[19] 张贵军. Cyclin D1和β-catenin在甲状腺癌组织中的蛋白表达[J].中国地方病防治杂志,2014,29(3): 174-176.

敲低S100A1通过降低WNT/β-catenin信号活性抑制甲状腺癌SW579细胞增殖

Down-Regulation of S100A1 Negatively Regulates Wnt/β- catenin Signaling Activity and Inhibits Proliferation of Thyroid Cancer SW579 Cells

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