Xiong Juan, Jiang Panpan, Zhong Li, Wang Youling
School of Public Health, Health Science Center, Shenzhen University, Shenzhen, China.
School of Life and Marine Sciences, Shenzhen University, Shenzhen, China.
Front Oncol. 2021 May 31;11:646511. doi: 10.3389/fonc.2021.646511. eCollection 2021.
Clinically, the effective treatment options available to thyroid cancer (THCA) patients are very limited. Elucidating the features of tumor suppressor genes (TSGs) and the corresponding signal transduction cascade may provide clues for the development of new strategies for targeted therapy of THCA. Therefore, this paper aims to explore the mechanism of ZNF24 underlying promoting THCA cell senescence at molecular level.
We performed RT-PCR and Western Blotting for evaluating associated RNA and protein expression. CCK8, colony forming, wound healing and Transwell chamber assays were conducted to examine THCA cell proliferation, invasion and migration. β-galactosidase staining assay was performed to detect THCA cells senescence. The size and volume of xenotransplanted tumors in nude mice are calculated to asses ZNF24 effect .
Ectopic expression of ZNF24 significantly inhibited the cell viability, colony forming, migration and invasion abilities of THCA cell lines (K1/GLAG-66i and BCPAPi) ( < 0.05). ZNF24 induced BCPAPi cells senescence through regulating Wnt signaling pathway. ZNF24 inhibited Wnt signaling pathway activition by competitively binding β-catenin from LEF1/TCF1-β-catenin complex. In nude mice, both Ectopic expression of ZNF24 and 2,4-Da (the strong β-catenin/Tcf-4 inhibitor) treatment significantly decreased both the size and weight of xenotransplanted tumors when compared with control mice ( < 0.05).
Results obtained and reveal the role of ZNF24 in significantly suppressing THCA tumorigenesis and invasion by regulating Wnt signaling pathway.
临床上，甲状腺癌（THCA）患者可用的有效治疗选择非常有限。阐明肿瘤抑制基因（TSGs）的特征及其相应的信号转导级联反应可能为开发THCA靶向治疗新策略提供线索。因此，本文旨在从分子水平探索ZNF24促进THCA细胞衰老的机制。
我们进行了逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法以评估相关RNA和蛋白质表达。进行细胞计数试剂盒-8（CCK8）、集落形成、伤口愈合和Transwell小室试验以检测THCA细胞的增殖、侵袭和迁移。进行β-半乳糖苷酶染色试验以检测THCA细胞衰老。计算裸鼠体内异种移植肿瘤的大小和体积以评估ZNF24的作用。
ZNF24的异位表达显著抑制了THCA细胞系（K1/GLAG-66i和BCPAPi）的细胞活力、集落形成、迁移和侵袭能力（P<0.05）。ZNF24通过调节Wnt信号通路诱导BCPAPi细胞衰老。ZNF24通过竞争性结合LEF1/TCF1-β-连环蛋白复合物中的β-连环蛋白来抑制Wnt信号通路的激活。在裸鼠中，与对照小鼠相比，ZNF24的异位表达和2,4-二氨基嘧啶（强力β-连环蛋白/Tcf-4抑制剂）处理均显著降低了异种移植肿瘤的大小和重量（P<0.05）。
所得结果揭示了ZNF24通过调节Wnt信号通路在显著抑制THCA肿瘤发生和侵袭中的作用。
