DZIP1通过影响Wnt/β-catenin信号通路促进口腔鳞状细胞癌增殖、迁移和侵袭

摘要/Abstract

摘要： 目的　探究DZIP1通过Wnt/β-catenin信号通路对口腔鳞状细胞癌增殖、迁移和侵袭的影响。方法　实时荧光定量PCR和Western blot检测DZIP1和Wnt/β-catenin信号通路相关基因mRNA表达和蛋白表达，CCK-8检测细胞活力，克隆形成实验检测口腔鳞状细胞癌（oral squamous cell carcinoma，OSCC）细胞增殖能力，Transwell实验检测细胞迁移和侵袭能力。结果　与人口腔角质形成细胞相比，人OSCC细胞系TSCCA，Tca8113和SCC25中DZIP1的mRNA表达和蛋白表达均显著升高；与阴性对照组（negative control，NC）相比，敲低DZIP1显著降低SCC25细胞Wnt/β-catenin信号通路相关基因的mRNA表达和蛋白表达（P<0.05），显著降低细胞活力（P<0.05），显著抑制细胞增殖（P<0.05），显著降低细胞迁移和侵袭能力（P<0.05），LiCl显著升高SCC25细胞Wnt/β-catenin信号通路相关基因的mRNA表达和蛋白表达（P<0.05），显著升高细胞活力（P<0.05），显著促进细胞增殖（P<0.05），显著升高细胞迁移和侵袭能力（P<0.05）；与si-DZIP1组相比，si-DZIP1+LiCl显著升高SCC25细胞Wnt/β-catenin信号通路相关基因的mRNA表达和蛋白表达（P<0.05），显著升高细胞活力（P<0.05），显著促进细胞增殖（P<0.05），显著升高细胞迁移和侵袭能力（P<0.05）。结论　DZIP1通过影响Wnt/β-catenin信号通路促进口腔鳞状细胞癌增殖、迁移和侵袭。

关键词: DZIP1, 口腔鳞状细胞癌, Wnt/β-catenin信号通路, 增殖, 迁移, 侵袭

Abstract: Abstract:　Objective　To investigate the effect of DZIP1 on the proliferation, migration and invasion of oral squamous cell carcinoma through the Wnt/β-catenin signaling pathway. Methods　Real-time quantitative PCR and Western blot were used to detect the mRNA and protein expression of genes related to DZIP1 and Wnt/β-catenin signaling pathway. Cell viability was detected by CCK-8. Oral squamous cell carcinoma(OSCC) was detected by clone formation to assay cell proliferation ability. Transwell assay was used to detect cell migration and invasion. Results　Compared with human oral keratinocytes(HOK), mRNA expression and protein expression of DZIP1 in human OSCC cell lines TSCCA, Tca8113 and SCC25 were significantly increased. Compared with the negative control(NC) group, knocking down DZIP1 significantly reduced the mRNA and protein expression of Wnt/β-catenin signaling pathway-related genes in SCC25 cells(P<0.05), and reduced cell viability(P<0.05), migration and invasion ability, inhibited cell proliferation(P<0.05). LiCl significantly increased the mRNA and protein expression of genes related to Wnt/β-catenin signaling pathway in SCC25 cells(P<0.05), increased cell viability(P<0.05), promoted cell proliferation(P<0.05), migration and invasion ability(P<0.05). Compared with the si-DZIP1 group, si-DZIP1 + LiCl significantly increased the mRNA and protein expression of genes related to the Wnt/β-catenin signaling pathway in SCC25 cells(P<0.05), and increased cell viability(P<0.05), promoted cell proliferation(P<0.05), migration and invasion capacity(P<0.05). Conclusion　DZIP1 promotes the proliferation, migration and invasion of oral squamous cell carcinoma by affecting the Wnt/β-catenin signaling pathway.

Key words: DZIP1, Oral squamous cell carcinoma, Wnt / β-catenin signaling pathway, Proliferation, Migration, Invasion

中图分类号:

R739.8

库都斯卡米力江徐前. DZIP1通过影响Wnt/β-catenin信号通路促进口腔鳞状细胞癌增殖、迁移和侵袭[J]. 口腔医学, 2021, 41(1): 12-17.

参考文献［1］

［1］

Seiwert T Y, Zuo Z, Keck M K, et al. Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas[J]. Clinical cancer research, 2015, 21(3): 632-641.［2］Cohen E E W, Davis D W, Karrison T G, et al. Erlotinib and bevacizumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck: a phase I/II study[J]. The lancet oncology, 2009, 10(3): 247-257.［3］Ding S, Qu W, Jiao Y, et al. LncRNA SNHG12 promotes the proliferation and metastasis of papillary thyroid carcinoma cells through regulating wnt/β-catenin signaling pathway[J]. Cancer Biomarkers, 2018, 22(2): 217-226.［4］MacDonald B T, Tamai K, He X. Wnt/β-catenin signaling: components, mechanisms, and diseases[J]. Developmental cell, 2009, 17(1): 9-26.［5］Zhao X, Xie T, Zhao W, et al. Downregulation of MMseT impairs breast cancer proliferation and metastasis through inhibiting Wnt/β-catenin signaling[J]. OncoTargets and therapy, 2019, 12: 1965.［6］Qina C J, Bua P L, Zhanga Q, et al. ZNF281 Regulates Cell Proliferation, Migration and Invasion in Colorectal Cancer through Wnt/β-Catenin Signaling[J]. Cell Physiol Biochem, 2019, 52: 1503-1516.［7］Hu X, Tan Z, Yang Y, et al. Long non‐coding RNA MIR22HG inhibits cell proliferation and migration in cholangiocarcinoma by negatively regulating the Wnt/β‐catenin signaling pathway[J]. The journal of gene medicine, 2019, 21(5): e3085.［8］Moore F L, Jaruzelska J, Dorfman D M, et al. Identification of a novel gene, DZIP (DAZ-interacting protein), that encodes a protein that interacts with DAZ (deleted in azoospermia) and is expressed in embryonic stem cells and germ cells[J]. Genomics, 2004, 83(5): 834-843.［9］Sekimizu K, Nishioka N, Sasaki H, et al. The zebrafish iguana locus encodes Dzip1, a novel zinc-finger protein required for proper regulation of Hedgehog signaling[J]. Development, 2004, 131(11): 2521-2532.［10］Ingham P W, McMahon A P. Hedgehog signaling in animal development: paradigms and principles[J]. Genes & development, 2001, 15(23): 3059-3087.［11］Katoh Y, Katoh M. WNT antagonist, SFRP1, is Hedgehog signaling target[J]. International journal of molecular medicine, 2006, 17(1): 171-175.［12］Shi J, Huang Y. Screen and classify genes on bladder cancer associated with metastasis[J]. Gene Reports, 2019: 100430.［13］Yan W, Deng Y, Zhang Y, et al. DZIP1 Promotes Proliferation, Migration, and Invasion of Oral Squamous Carcinoma Through the GLI1/3 Pathway[J]. Translational oncology, 2019, 12(11): 1504-1515.［14］邱峰, 王潇悦, 赵军方, et al. 亚砷酸钠调控Wnt信号通路抑制口腔鳞状细胞癌增殖及促进凋亡的机制研究[J]. 中国生化药物杂志(4).［15］Hunter K D, Parkinson E K, Harrison P R. Profiling early head and neck cancer[J]. Nature Reviews Cancer, 2005, 5(2): 127.［16］Eder-Czembirek C, Rechinger S, Kornek G, et al. Experience in Intra-arterial Chemotherapy using Two Protocols for the Treatment of OSCC over Two Decades at the University Hospital Vienna[J]. Clinics, 2018, 73.［17］Gotwals P, Cameron S, Cipolletta D, et al. Prospects for combining targeted and conventional cancer therapy with immunotherapy[J]. Nature Reviews Cancer, 2017, 17(5): 286.［18］Jiang W, Yuan H, Chan C K, et al. Lessons from immuno-oncology: a new era for cancer nanomedicine?[J]. Nature Reviews Drug Discovery, 2017, 16(6): 369.［19］Zhang K, Liu P, Tang H, et al. AFAP1-AS1 promotes epithelial-mesenchymal transition and tumorigenesis through Wnt/β-catenin signaling pathway in triple-negative breast cancer[J]. Frontiers in pharmacology, 2018, 9.［20］Xu S, Fan Y, Li D, et al. Glycoprotein nonmetastatic melanoma protein B accelerates tumorigenesis of cervical cancer in vitro by regulating the Wnt/β-catenin pathway[J]. Brazilian Journal of Medical and Biological Research, 2019, 52(1).［21］Yang J, Ye Z, Mei D, et al. long noncoding Rna DlX6-as1 promotes tumorigenesis by modulating miR-497-5p/FZD4/FZD6/Wnt/β-catenin pathway in pancreatic cancer[J]. Cancer management and research, 2019, 11: 4209.［22］Pai S G, Carneiro B A, Mota J M, et al. Wnt/beta-catenin pathway: modulating anticancer immune response[J]. Journal of hematology & oncology, 2017, 10(1): 101.［23］Jiang R, Niu X, Huang Y, et al. β-Catenin is important for cancer stem cell generation and tumorigenic activity in nasopharyngeal carcinoma[J]. Acta Biochim Biophys Sin, 2016, 48(3): 229-237.［24］Rong L, Zhao R, Lu J. Highly expressed long non-coding RNA FOXD2-AS1 promotes non-small cell lung cancer progression via Wnt/β-catenin signaling[J]. Biochemical and biophysical research communications, 2017, 484(3): 586-591.［25］Zhang L, Song Y, Ling Z, et al. R-spondin 2-LGR4 system regulates growth, migration and invasion, epithelial-mesenchymal transition and stem-like properties of tongue squamous cell carcinoma via Wnt/β-catenin signaling[J]. EBioMedicine, 2019.

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