癌症研究
表皮生长因子受体
蛋白激酶B
乳腺癌
吉非替尼
细胞生长
PI3K/AKT/mTOR通路
癌症
化学
信号转导
生物
内科学
医学
细胞生物学
生物化学
作者
Xintao Jing,Cong Han,Qian Li,Zhenguang Li,Qian Zhang,Qiuyu Jiang,Fei Zhao,Guo Chen,Jinfeng Chen,Ting Jiang,Xiaofei Wang,Yanke Chen,Chen Huang
标识
DOI:10.1016/j.bbamcr.2023.119542
摘要
Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) is an emerging prognostic indicator, and its elevated expression correlates with malignancy in a broad spectrum of cancers. However, its regulatory networks have not yet been reported. In this study, we identified the regulatory targets of IGF2BP3 in breast cancer MDA-MB-231 cells using RNA immunoprecipitation sequencing (RIP-seq) and high-throughput RNA-sequencing (RNA-seq). We discovered that these targets were enriched in the inflammatory response, endoplasmic reticulum stress, cell cycle, and cancer-related pathways, providing a new perspective for better understanding the functional mechanisms of IGF2BP3. Moreover, we identified that the epidermal growth factor receptor (EGFR), a downstream target, is regulated by IGF2BP3. IGF2BP3 binds to and protects EGFR mRNA from degradation and facilitates cell proliferation via the EGFR/AKT pathway in MDA-MB-231 cells. In addition, IGF2BP3 expression was robust and could not be altered by stimulation with EGF and anti-EGFR siRNA or EGFR signaling pathway inhibitors (gefitinib, LY294002 and SL-327). These results demonstrate that IGF2BP3, as a stubborn oncogene, promotes triple-negative breast cancer MDA-MB-231 cell proliferation by strengthening the role of the EGFR-AKT axis.
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