Luo Guirong, Zhang Liting, Wu Wenyi, Zhang Lihong, Lin Jianqing, Shi Haihong, Wu Xinquan, Yu Yihuang, Qiu Weigang, Chen Jinyan, Ding Hansen, Chen Xinyao
Department of Thyroid and Breast Surgery, The Second Affiliated Clinical School of Medicine, Fujian Medical University, Quanzhou, Fujian 362000, P.R. China.
Department of Endocrinology, The Number 910 Hospital, The Joint Logistics Support Force, Quanzhou, Fujian 362000, P.R. China.
Oncol Lett. 2023 Jul 17;26(3):370. doi: 10.3892/ol.2023.13956. eCollection 2023 Sep.
Aberrant ubiquitination contributes to cancer development, including thyroid carcinoma. The present study assessed the expression of ubiquitin carboxy-terminal hydrolase 47 (USP47) and underlying molecular events in the development of papillary thyroid carcinoma (PTC). The effects of USP47 on PTC cell invasion and migration were analyzed by Transwell assays, while. the effects of USP47 and SATB1on PTC cell gene expression and changes in tumor cell metabolism were assayed by reverse transcription-quantitative PCR, western bolt, or ELISA, respectively. The expression of USP47 mRNA and protein was upregulated in PTC tissue and associated with the PTC tumor size. Knockdown of USP47 expression in PTC cell lines (TPC-1 and K1), decreased the cell proliferation mobility and invasion capacities, whereas USP47 overexpression in these cell lines showed an inverse effect and promoted cell glycolysis and glutamine metabolism. Moreover, expression of special AT-rich sequence-binding protein-1 (SATB1) was high in PTC tissue and was associated with USP47 expression. SATB1 expression promoted tumor cell glycolysis and glutamine metabolism, while USP47 protein bound to and deubiquitinated SATB1 to increase its intracellular levels, thus promoting glycolysis and glutamine metabolism. USP47 promotion of PTC development may be due to its stabilization of SATB1 protein, suggesting that targeting the USP47/SATB1 signaling axis may serve as a therapeutic intervention for PTC.
异常的泛素化作用有助于癌症的发展，包括甲状腺癌。本研究评估了泛素羧基末端水解酶47（USP47）的表达以及甲状腺乳头状癌（PTC）发展过程中的潜在分子事件。通过Transwell实验分析了USP47对PTC细胞侵袭和迁移的影响，同时分别通过逆转录定量PCR、蛋白质免疫印迹法或酶联免疫吸附测定法检测了USP47和SATB1对PTC细胞基因表达及肿瘤细胞代谢变化的影响。USP47 mRNA和蛋白在PTC组织中表达上调，且与PTC肿瘤大小相关。在PTC细胞系（TPC-1和K1）中敲低USP47表达，可降低细胞增殖、迁移和侵袭能力，而在这些细胞系中过表达USP47则呈现相反的效果，并促进细胞糖酵解和谷氨酰胺代谢。此外，富含AT序列结合蛋白1（SATB1）在PTC组织中高表达，且与USP47表达相关。SATB1表达促进肿瘤细胞糖酵解和谷氨酰胺代谢，而USP47蛋白与SATB1结合并使其去泛素化，以增加其细胞内水平，从而促进糖酵解和谷氨酰胺代谢。USP47促进PTC发展可能是由于其对SATB1蛋白的稳定作用，这表明靶向USP47/SATB1信号轴可能作为PTC的一种治疗干预手段。
