期刊
CANCER SCIENCE
卷 111, 期 2, 页码 637-646出版社
WILEY
DOI: 10.1111/cas.14226
关键词
glycolysis; lung adenocarcinoma; NF-kappa B; resistance; TRIM23
类别
资金
- National Natural Science Foundation of China [81472615, 81600044]
The tripartite motif containing 23 (TRIM23) gene is a member of the tripartite motif (TRIM) family that participates in many pathophysiological processes. However, the role of TRIM23 in lung adenocarcinoma (LUAD) remains unclear. In the present study, TRIM23 was first screened by next-generation sequencing between the cisplatin (DDP)-resistant A549/DDP cell line and the parental A549 cell line, combined with integrated analysis of the Gene Expression Omnibus (GEO) data (E-GEOD-43493 and E-GEOD-43494). The expression of TRIM23 was then verified to be upregulated in the DDP-resistant LUAD cells and tissues. The knockdown of TRIM23 expression in A549/DDP cells caused increased apoptosis, decreased IC50 values of DDP, NF-kappa B nuclear translocation, inhibition of cell proliferation in vitro and in vivo, inhibition of GLUT1/3 expression, glucose uptake, and lactate and ATP production. TRIM23 overexpression resulted in the opposite effects in A549 cells. In addition, the inhibition of proliferation in A549 cells caused by NF-kappa B signaling inhibitor PTDC or glycolysis inhibitor 3-BrPA could be weakened by TRIM23 overexpression. Furthermore, immunohistochemical analysis revealed that TRIM23 was upregulated in 46.1% (70/152) of LUAD cases, and elevated TRIM23 expression was correlated with high expression of NF-kappa B, poor cellular differentiation, and adverse overall survival (OS) and disease-free survival (DFS). In conclusion, our study demonstrates that TRIM23 acts as an oncogene in LUAD and promotes DDP resistance by regulating glucose metabolism via the TRIM23/NF-kappa B/ GLUT1/3 axis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据