TBK1 通过激活 PI3K/Akt/mTOR 信号通路促进甲状腺癌进展。

TBK1 promotes thyroid cancer progress by activating the PI3K/Akt/mTOR signaling pathway.

机构信息

Department of Pathology, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, Fujian, P. R. China.

出版信息

Immun Inflamm Dis. 2023 Mar;11(3):e796. doi: 10.1002/iid3.796.

INTRODUCTION

Thyroid cancer has received increasing attention; however, its detailed pathogenesis and pathological processes remain unclear. We investigated the role of TANK-binding kinase 1 (TBK1) in the progression of thyroid cancer.

METHODS

The expression of TBK1 in thyroid cancer and normal control tissues was analyzed using real-time quantitative polymerase chain reaction. The function of TBK1 on thyroid cancer cells was detected using MTT, colony formation, wound healing, and Transwell assays. The xenograft assay was carried out to check on the role of TBK1 in thyroid cancer.

RESULTS

TBK1 was highly expressed in thyroid tumors. High expression of TBK1 raised viability, proliferation, migration, and invasion of thyroid cancer cells. Gene set enrichment analysis revealed that TBK1 activated the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway. In addition, Myc-associated zinc finger protein (MAZ) was overexpressed in thyroid cancer and transcriptionally activated BK1. MAZ silence reversed the effects of TBK1 overexpression on thyroid cancer progression. Cotransfection with MAZ small-interfering RNA(siRNA) and TBK1 siRNA did not strengthen the inhibitory effect of TBK1 silencing on the thyroid cancer cells. The xenograft tumor assay showed that TBK1 short hairpinRNA inhibited tumor growth.

CONCLUSION

MAZ silencing inhibited tumor progress of thyroid cancer cells, whereas this inhibitory effect was reversed by TBK1 overexpression.

简介

甲状腺癌受到越来越多的关注；然而，其详细的发病机制和病理过程仍不清楚。我们研究了 TANK 结合激酶 1（TBK1）在甲状腺癌进展中的作用。

方法

使用实时定量聚合酶链反应分析甲状腺癌和正常对照组织中 TBK1 的表达。使用 MTT、集落形成、划痕愈合和 Transwell 测定检测 TBK1 对甲状腺癌细胞的功能。进行异种移植实验以检查 TBK1 在甲状腺癌中的作用。

结果

TBK1 在甲状腺肿瘤中高表达。TBK1 高表达可提高甲状腺癌细胞的活力、增殖、迁移和侵袭能力。基因集富集分析显示 TBK1 激活了磷脂酰肌醇-3-激酶/蛋白激酶 B/雷帕霉素靶蛋白途径。此外，在甲状腺癌中 MAZ（Myc-associated zinc finger protein）过表达并转录激活 TBK1。沉默 MAZ 逆转了 TBK1 过表达对甲状腺癌进展的影响。MAZ 小干扰 RNA（siRNA）和 TBK1 siRNA 的共转染并没有增强 TBK1 沉默对甲状腺癌细胞的抑制作用。异种移植肿瘤实验表明，TBK1 短发夹 RNA 抑制了肿瘤的生长。