Du Xin, Wang Jia-Mei, Zhang Da-Lin, Wu Tong, Zeng Xiao-Yan, Jiang Jing-Yi, Du Zhen-Xian
Department of Endocrinology and Metabolism, The First Affiliated Hospital of China Medical University, Shenyang, China.
Department of Laboratory Medicine, The First Affiliated hospital of China Medical University, Shenyang, China.
Front Oncol. 2021 Jun 16;11:681736. doi: 10.3389/fonc.2021.681736. eCollection 2021.
The pathogenesis of papillary thyroid cancer (PTC), the most common type of thyroid cancer, is not yet fully understood. This limits the therapeutic options for approximately 7% of invasive PTC patients. The critical role of AUF1 in the progression of thyroid cancer was first reported in 2009, however, its molecular mechanism remained unclear. Our study used CRISPR/Cas 9 system to knockdown AUF1 in IHH4 and TPC1 cells. We noticed that the expression of TRIM58 and ZBTB2 were increased in the AUF1 knockdown IHH4 and TPC1 cells. When TRIM58 and ZBTB2 were inhibited by small hairpin RNAs (shRNAs) against TRIM58 (shTRIM58) and ZBTB2 (shZBTB2), respectively, the proliferation, migration, and invasion ability of the AUF1-knockdown IHH4 and TPC1 cells were increased. In addition, two ZBTB2 binding sites (-719-709 and -677-668) on TRIM58 promoter and two AUF1 binding sites (1250-1256 and 1258-1265) on ZBTB2 3'-UTR were identified. These results suggested that AUF1 affecting thyroid cancer cells regulating the expression of ZBTB2 and TRIM58.
甲状腺癌最常见的类型是乳头状甲状腺癌（PTC），其发病机制尚未完全明确。这限制了约7%的侵袭性PTC患者的治疗选择。2009年首次报道了AUF1在甲状腺癌进展中的关键作用，然而，其分子机制仍不清楚。我们的研究使用CRISPR/Cas 9系统敲低IHH4和TPC1细胞中的AUF1。我们注意到，在敲低AUF1的IHH4和TPC1细胞中，TRIM58和ZBTB2的表达增加。当分别用针对TRIM58（shTRIM58）和ZBTB2（shZBTB2）的小发夹RNA（shRNA）抑制TRIM58和ZBTB2时，敲低AUF1的IHH4和TPC1细胞的增殖、迁移和侵袭能力增强。此外，在TRIM58启动子上鉴定出两个ZBTB2结合位点（-719-709和-677-668），在ZBTB2 3'-UTR上鉴定出两个AUF1结合位点（1250-1256和1258-1265）。这些结果表明，AUF1通过调节ZBTB2和TRIM58的表达影响甲状腺癌细胞。
