SEMA3C promotes thyroid cancer via the Wnt/β-catenin pathway.

IF 3.3 3区 生物学 Q3 CELL BIOLOGY Experimental cell research Pub Date : 2024-12-10 DOI:10.1016/j.yexcr.2024.114378
Shiwei Li, Yanmei Cheng, Changhui Gao, Qingling Yuan, Xiubo Lu
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引用次数: 0

Abstract

Semaphorin 3C (SEMA3C) regulates the progression of several tumors. However, the role of SEMA3C in thyroid cancer remains unknow. In the present study, SEMA3C was overexpressed or knocked down in thyroid cancer cell lines BCPAP and IHH-4. It was found that SEMA3C promoted the cell migration, invasion, and mesenchymal-epithelial transition (EMT) process. SEMA3C overexpression enhanced tumor cell stemness, while SEMA3C knockdown showed the opposite effects. In vivo experiments suggested that SEMA3C accelerated the tumor growth and metastasis. Moreover, SEMA3C enhanced β-catenin nuclear translocation. When cells were treated with Dickkopf-1 (DKK1), an inhibitor of Wnt/β-catenin pathway, the promoting effects of SEMA3C on cell migration and stemness were offset. Wnt/β-catenin pathway mediated the roles of SEMA3C in thyroid cancer. Additionally, an upstream regulator of SEMA3C was identified. E1A binding protein P300 (P300) was found to increase the histone three lysine 27 acetylation (H3K27ac) level of SEMA3C, promoting its transcriptional activation. Therefore, we clarify that SEMA3C exerts a tumor-promoting effect on thyroid cancer, and Wnt/β-catenin pathway is the critical downstream pathway.

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半隐性蛋白3C(SEMA3C)调节多种肿瘤的进展。然而,SEMA3C在甲状腺癌中的作用仍然未知。在本研究中,SEMA3C在甲状腺癌细胞系BCPAP和IHH-4中被过表达或敲除。研究发现,SEMA3C能促进细胞迁移、侵袭和间质-上皮转化(EMT)过程。过表达SEMA3C会增强肿瘤细胞的干性,而敲除SEMA3C则会产生相反的效果。体内实验表明,SEMA3C会加速肿瘤的生长和转移。此外,SEMA3C还能增强β-catenin的核转位。当用Wnt/β-catenin通路抑制剂Dickkopf-1(DKK1)处理细胞时,SEMA3C对细胞迁移和干性的促进作用被抵消。Wnt/β-catenin通路介导了SEMA3C在甲状腺癌中的作用。此外,还发现了SEMA3C的上游调节因子。研究发现,E1A结合蛋白P300(P300)能提高SEMA3C的组蛋白三赖氨酸27乙酰化(H3K27ac)水平,促进其转录激活。因此,我们明确了SEMA3C对甲状腺癌具有促瘤作用,而Wnt/β-catenin通路是其关键的下游通路。
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来源期刊
Experimental cell research
Experimental cell research 医学-细胞生物学
CiteScore
7.20
自引率
0.00%
发文量
295
审稿时长
30 days
期刊介绍: Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.
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