AUF1 Promotes Proliferation and Invasion of Thyroid Cancer via Downregulation of ZBTB2 and Subsequent TRIM58.

AUF1 Promotes Proliferation and Invasion of Thyroid Cancer via Downregulation of ZBTB2 and Subsequent TRIM58.
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AUF1通过下调ZBTB2和随后的TRIM58促进甲状腺癌的增殖和侵袭

DOI:
10.3389/fonc.2021.681736
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发表时间:
2021
影响因子:
4.7
通讯作者:
Du ZX
Du ZX
中科院分区:
医学3区
文献类型:
--
作者:
Du X;Wang JM;Zhang DL;Wu T;Zeng XY;Jiang JY;Du ZX

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甲状腺乳头状癌(PTC)是最常见的甲状腺癌类型,其发病机制尚未完全了解。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AUF 1在甲状腺癌进展中的关键作用,但其分子机制仍不清楚。我们的研究使用CRISPR/Cas 9系统敲低IHH 4和TPC 1细胞中的AUF 1。我们注意到,在AUF 1敲低的IHH 4和TPC 1细胞中,TRIM 58和ZBTB 2的表达增加。当TRIM 58和ZBTB 2分别被针对TRIM 58(shTRIM 58)和ZBTB 2(shZBTB 2)的小发夹RNA(shRNAs)抑制时,AUF 1敲低的IHH 4和TPC 1细胞的增殖、迁移和侵袭能力增加。另外,在TRIM 58启动子上发现了两个ZBTB 2结合位点(-719~-709和-677~-668),在ZBTB 2 3 '-UTR上发现了两个AUF 1结合位点(1250-1256和1258-1265)。提示AUF 1可能通过调控ZBTB 2和TRIM 58的表达而影响甲状腺癌细胞。
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 via regulating the expression of ZBTB2 and TRIM58.
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