当前位置: X-MOL 学术Biochem. Biophys. Res. Commun. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Effect of TNIK upregulation on JQ1-resistant human colorectal cancer HCT116 cells.
Biochemical and Biophysical Research Communications ( IF 2.5 ) Pub Date : 2020-08-03 , DOI: 10.1016/j.bbrc.2020.06.136
Chihiro Takahashi 1 , Shingo Kondo 1 , Kensuke Sadaoka 1 , Shuhei Ishizuka 1 , Kohji Noguchi 1 , Yu Kato 1 , Yoshikazu Sugimoto 1
Affiliation  

JQ1 disrupts the binding of bromodomain and extra-terminal (BET) family of proteins to acetylated histones, modulates the expression of various genes, and inhibits the proliferation of cancer cells. We established two JQ1-resistant sublines from human colorectal cancer HCT116 cells. These resistant cells showed an 8- to 9-fold higher resistance to JQ1, and a 2- to 4-fold higher resistance to various anti-cancer agents, such as doxorubicin, etoposide, mitoxantrone, SN-38, cisplatin, and methotrexate than the parental HCT116 cells. The JQ1-resistant cells expressed higher levels of TRAF2 and NCK-interacting protein kinase (TNIK), cyclin D1 (CCND1), cyclin E1 (CCNE1), and their corresponding mRNAs than the parental cells. TNIK is a regulator of Wnt/β-catenin signaling and is known to transactivate CCND1. Transient transfection of HCT116 cells with a TNIK expression plasmid resulted in the upregulation of cyclin D1, cyclin E1, and their corresponding mRNAs, as well as an increase in CCNE1 promoter activity. Furthermore, luciferase assay revealed that the JQ1-resistant cells showed high CCNE1 promoter activity. These results suggest that TNIK also transactivates CCNE1. Three stable TNIK transfectant clones of HEK293 cells expressed 1.5- to 2-fold higher levels of TNIK, cyclin D1, and cyclin E1 than the parental cells. The 293/TNIK-6 cells, which expressed the highest level of TNIK among the transfectants, showed a 2.3-fold higher resistance to JQ1 than the parental cells. These results suggest the possible involvement of TNIK in cellular resistance to JQ1.



中文翻译:

TNIK上调对JQ1抗性大肠癌HCT116细胞的影响。

JQ1破坏了溴结构域和蛋白质的末端外(BET)家族与乙酰化组蛋白的结合,调节了各种基因的表达,并抑制了癌细胞的增殖。我们从人结肠直肠癌HCT116细胞建立了两个抗JQ1的亚系。这些抗性细胞对JQ1的抗性比对阿霉素,依托泊苷,米托蒽醌,SN-38,顺铂和甲氨蝶呤的抗JQ1的抗性高8至9倍,对抗QQ2的抗性高2至4倍。亲本HCT116细胞。与亲代细胞相比,JQ1抗性细胞表达更高水平的TRAF2和与NCK相互作用的蛋白激酶(TNIK),细胞周期蛋白D1(CCND1),细胞周期蛋白E1(CCNE1)及其相应的mRNA。TNIK是Wnt /β-catenin信号的调节剂,已知会激活CCND1。用TNIK表达质粒瞬时转染HCT116细胞会导致细胞周期蛋白D1,细胞周期蛋白E1及其相应的mRNA上调,以及CCNE1启动子活性的增加。此外,荧光素酶测定法显示JQ1抗性细胞显示高CCNE1启动子活性。这些结果表明TNIK也可以激活CCNE1。三个稳定的TNIK与亲代细胞相比,HEK293细胞的转染克隆表达的TNIK,细胞周期蛋白D1和细胞周期蛋白E1的水平高1.5至2倍。293 / TNIK-6细胞在转染子中表达最高水平的TNIK,对JQ1的抗性比亲代细胞高2.3倍。这些结果表明,TNIK可能参与了细胞对JQ1的抗性。

更新日期:2020-08-04
down
wechat
bug