生物
MAPK/ERK通路
癌症研究
细胞生物学
基因敲除
磷酸化
基因沉默
细胞生长
癌变
p38丝裂原活化蛋白激酶
信号转导
细胞凋亡
癌症
生物化学
遗传学
基因
作者
Chunji Chen,Dongfang Tang,Shaohua Xu,Lujie Xiang,Yun Song,Yuanshan Yao,Zheng Li,Siyun Lin,S Li,Xin Shi,Chang Gu,Wen Gao
摘要
Abstract Reactive oxygen species (ROS) are metabolic by‐products of cells, and abnormal changes in their levels are often associated with tumor development. Our aim was to determine the role of collagen and calcium binding EGF domain 1 (CCBE1) in oxidative stress and tumorigenesis in non‐small cell lung cancer cells (NSCLC). We investigated the tumorigenic potential of CCBE1 in NSCLC using in vitro and in vivo models of CCBE1 overexpression and knockdown. Immunohistochemical staining results showed that the expression of CCBE1 in cancer tissues was significantly higher than that in adjacent tissues. Cell counting Kit 8, clonal formation, wound healing, and transwell experiments showed that CCBE1 gene knockdown significantly inhibited the migration, invasion, and proliferation of NSCLC cell lines. In terms of mechanism, the silencing of CCBE1 can significantly promote the morphological abnormalities of mitochondria, significantly increase the intracellular ROS level, and promote cell apoptosis. This change of oxidative stress can affect cell proliferation, migration, and invasion by regulating the phosphorylation level of ERK/JNK/P38 MAPK. Specifically, the downregulation of CCBE1 inhibits the phosphorylation of ERK/P38 and promotes the phosphorylation of JNK in NSCLC, and this regulation can be reversed by the antioxidant NAC. In vivo experiments confirmed that downregulating CCBE1 gene could inhibit the growth of NSCLC in BALB/c nude mice. Taken together, our results confirm the tumorigenic role of CCBE1 in promoting tumor invasion and migration in NSCLC, and reveal the molecular mechanism by which CCBE1 regulates oxidative stress and the ERK/JNK/P38 MAPK pathway.
科研通智能强力驱动
Strongly Powered by AbleSci AI