Negative feedback regulation of AXL by miR-34a modulates apoptosis in lung cancer cells

Chun Yu Cho, Jhy Shrian Huang, Shine Gwo Shiah, Shih Ying Chung, Jong Ding Lay, Ya Yu Yang, Gi Ming Lai, Ann Lii Cheng, Li Tzong Chen, Shuang En Chuang

研究成果: 雜誌貢獻文章

18 引文 斯高帕斯(Scopus)

摘要

The AXL receptor tyrosine kinase is frequently overexpressed in cancers and is important in cancer invasion/metastasis and chemoresistance. Here, we demonstrate a regulatory feedback loop between AXL and microRNA (miRNA) at the posttranscriptional level. Both the GAS6-binding domain and the kinase domain of AXL, particularly the Y779 tyrosine phosphorylation site, are shown to be crucial for this autoregulation. To clarify the role of miRNAs in this regulation loop, approaches using bioinformatics and molecular techniques were applied, revealing that miR-34a may target the 3' UTR of AXL mRNA to inhibit AXL expression. Interestingly and importantly, AXL overexpression may induce miR-34a expression by activating the transcription factor ELK1 via the JNK signaling pathway. In addition, ectopic overexpression of ELK1 promotes apoptosis through, in part, down-regulation of AXL. Therefore, we propose that AXL is autoregulated by miR-34a in a feedback loop; this may provide a novel opportunity for developing AXL-targeted anticancer therapies.
原文英語
頁(從 - 到)303-315
頁數13
期刊RNA
22
發行號2
DOIs
出版狀態已發佈 - 二月 1 2016

ASJC Scopus subject areas

  • Molecular Biology

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    Cho, C. Y., Huang, J. S., Shiah, S. G., Chung, S. Y., Lay, J. D., Yang, Y. Y., Lai, G. M., Cheng, A. L., Chen, L. T., & Chuang, S. E. (2016). Negative feedback regulation of AXL by miR-34a modulates apoptosis in lung cancer cells. RNA, 22(2), 303-315. https://doi.org/10.1261/rna.052571.115