Sun Huali, Chen Qi, Liu Weiping, Liu Yanmei, Ruan Sihan, Zhu Chumeng, Ruan Yanyun, Ying Shenpeng, Lin Peipei
Department of Radiotherapy, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, P. R. China.
Precision Medicine Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, P. R. China.
J Cancer. 2021 Sep 27;12(22):6883-6893. doi: 10.7150/jca.62461. eCollection 2021.
Tumor-associated calcium signal transducer 2 (TROP2) is over expressed in various kinds of human cancers and plays important roles in the proliferation, invasion and metastasis of tumor cells. However, the expression and molecular mechanism of TROP2 in thyroid papillary carcinoma (PTC) are unclear. The expressions of TROP2 in PTC and control tissue were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. The proliferation and invasion of PTC cell lines were examined by cell cloning and transwell assays. RNA sequencing analysis and public data analysis were assessed to investigate the potential mechanisms of TROP2 in PTC. Gene correlation analysis was conducted to explore the association between TROP2 and the related gene ISG15 in patients with PTC. The expression of TROP2 was significantly higher in PTC than control. The high expression of TROP2 protein was associated with lymph node metastasis, tumor size and capsular infiltration (P<0.05). SiRNA-mediated TROP2 gene expression silencing can significantly inhibit proliferation and migration of PTC cells. ISG15 decreased in TROP2 siRNA PTC cells and increased in PTC patients significantly. There was a significant correlation between the expression of TROP2 and ISG15 in PTC patients. TROP2 interacted directly with ATP6V1A, CEBPA and SOX5 and then further interacted with the immune genes. TROP2 expression and tumor-infiltrating immune cells were also correlated in thyroid cancer microenvironment. TROP2 promotes the development of PTC. TROP2 expression was correlated with ISG15 and tumor-infiltrating immune cells in thyroid cancer.
肿瘤相关钙信号转导蛋白2(TROP2)在多种人类癌症中高表达,并在肿瘤细胞的增殖、侵袭和转移中发挥重要作用。然而,TROP2在甲状腺乳头状癌(PTC)中的表达及分子机制尚不清楚。通过实时逆转录聚合酶链反应(RT-PCR)和免疫组织化学检测PTC和对照组织中TROP2的表达。通过细胞克隆和Transwell实验检测PTC细胞系的增殖和侵袭能力。通过RNA测序分析和公共数据分析来研究TROP2在PTC中的潜在机制。进行基因相关性分析以探讨PTC患者中TROP2与相关基因ISG15之间的关联。PTC中TROP2的表达明显高于对照组。TROP2蛋白的高表达与淋巴结转移、肿瘤大小和包膜浸润相关(P<0.05)。小干扰RNA(SiRNA)介导的TROP2基因表达沉默可显著抑制PTC细胞的增殖和迁移。在TROP2小干扰RNA处理的PTC细胞中ISG15表达降低,而在PTC患者中ISG15表达显著增加。PTC患者中TROP2与ISG15的表达之间存在显著相关性。TROP2直接与ATP6V1A、CEBPA和SOX5相互作用,然后进一步与免疫基因相互作用。在甲状腺癌微环境中,TROP2表达与肿瘤浸润免疫细胞也相关。TROP2促进PTC的发展。在甲状腺癌中,TROP2表达与ISG15及肿瘤浸润免疫细胞相关。