RBM4-SRSF3-MAP4K4 splicing cascade modulates the metastatic signature of colorectal cancer cell

Jung Chun Lin, Yuan Chii Lee, Tse Hua Tan, Yu Chih Liang, Huai Chia Chuang, Yang C. Fann, Kory R. Johnson, Ying Ju Lin

研究成果: 雜誌貢獻文章

14 引文 斯高帕斯(Scopus)

摘要

Alternative splicing (AS) of pre-messenger (m)RNA is a pivotal mechanism in expanding proteomic diversity, which determines the functions of mammalian cells. By conducting transcriptome analyses to profile splicing events in human colorectal cancer (CRC) tissues compared to adjacent normal counterparts, we noted differential splicing profiles of serine/arginine-rich splicing factor 3 (SRSF3) and mitogen-activated protein 4 kinase 4 (MAP4K4) in cancerous tissues of CRC compared to adjacent normal tissues. In addition to SRSF3-mediated autoregulation, RNA-binding motif protein 4 (RBM4) constituted another mechanism in reprogramming the splicing profile of SRSF3. Upregulated expressions of SRSF3 in CRC cells modulated utilization of MAP4K4 exon 16 in a sequence-dependent manner. Alternatively spliced MAP4K4 variants exhibited differential effects on the phosphorylation of c-Jun N-terminal protein kinase 1 (JNK1) which subsequently modulated expression profiles of E-cadherin, N-cadherin, and vimentin, all of which are involved in the migration and invasion of CRC cells. Collectively, RBM4-SRSF3-MAP4K4 constitutes a novel mechanism for manipulating the metastasis of CRC cells through the JNK1 signaling pathway.
原文英語
頁(從 - 到)259-272
頁數14
期刊Biochimica et Biophysica Acta - Molecular Cell Research
1865
發行號2
DOIs
出版狀態已發佈 - 二月 1 2018

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

指紋 深入研究「RBM4-SRSF3-MAP4K4 splicing cascade modulates the metastatic signature of colorectal cancer cell」主題。共同形成了獨特的指紋。

  • 引用此