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SHCBP1 通过促进整合素和胶原的形成并维持细胞干性来促进甲状腺乳头状癌的发生和进展。

SHCBP1 Promotes Papillary Thyroid Carcinoma Carcinogenesis and Progression Through Promoting Formation of Integrin and Collagen and Maintaining Cell Stemness.

机构信息

Department of Endocrinology, Affiliated Hospital of Medical College of Southeast University and Xuzhou Central Hospital, Xuzhou, China.

Xuzhou Clinical School, Xuzhou Medical University, Xuzhou, China.

出版信息

Front Endocrinol (Lausanne). 2021 Feb 26;11:613879. doi: 10.3389/fendo.2020.613879. eCollection 2020.

Abstract

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer with a rapidly increasing incidence globally. Bioinformatics analyses suggested that SHCBP1 (SHC SH2 Domain-Binding Protein 1) was significantly up-regulated in PTC tumor tissues, which was further confirmed by immunohistochemical staining and qPCR analyses in Xuzhou cohort. Moreover, the results indicated that the mRNA level of was negatively associated with patients' disease-free survival rate, and further analysis reveals that patients with high SHCBP1 expression tend to have more lymph node metastasis. Afterward, MTT, colony formation, cell-cycle assay, FACS apoptosis assay, invasion, migration, as well as scratch assay were performed to study the phenotypes change of PTC cells after knocking down SHCBP1. The subcutaneous tumor model was developed to study the proliferation ability of PTC cells after SHCBP1 knockdown. We show that knock down of SHCBP1 significantly inhibits PTC cell proliferation, cell cycle, invasion and migration and . Western blot and qRT-PCR showed that knockdown of SHCBP1 could significantly reduce MYC, KLF4, CD44, ITGA6, ITGB1, ITGB5, and COL4A2 expression at both RNA and protein levels, which indicated that SHCBP1 might be involved in PTC carcinogenesis and progression through targeting formation of integrin and collagen and cell stemness pathways, and can be a potential diagnosis biomarker and therapeutic target for PTC.

摘要

甲状腺乳头状癌(PTC)是最常见的甲状腺癌,全球发病率呈快速上升趋势。生物信息学分析表明,SHCBP1(SHC SH2 结构域结合蛋白 1)在 PTC 肿瘤组织中显著上调,这在徐州队列的免疫组织化学染色和 qPCR 分析中得到了进一步证实。此外,研究结果表明,的 mRNA 水平与患者无病生存率呈负相关,进一步分析表明,高 SHCBP1 表达的患者往往有更多的淋巴结转移。随后,进行了 MTT、集落形成、细胞周期分析、FACS 凋亡分析、侵袭、迁移以及划痕实验,以研究敲低 SHCBP1 后 PTC 细胞表型的变化。建立了皮下肿瘤模型,以研究敲低 SHCBP1 后 PTC 细胞的增殖能力。我们发现,敲低 SHCBP1 可显著抑制 PTC 细胞的增殖、细胞周期、侵袭和迁移。Western blot 和 qRT-PCR 显示,敲低 SHCBP1 可显著降低 MYC、KLF4、CD44、ITGA6、ITGB1、ITGB5 和 COL4A2 的 RNA 和蛋白水平表达,表明 SHCBP1 可能通过靶向整合素和胶原形成以及细胞干性途径参与 PTC 的发生和发展,并且可以作为 PTC 的潜在诊断标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4296/7953042/443e32deca53/fendo-11-613879-g001.jpg

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