The impact of RNA binding motif protein 4-regulated splicing cascade on the progression and metabolism of colorectal cancer cells
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Yu-Chih Liang1,*, Wei-Cheng Lin2,*, Ying-Ju Lin3, Jung-Chun Lin1
1School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
2Division of Thoracic Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
3School of Chinese Medicine, China Medical University, Taichung, Taiwan
*These authors have contributed equally to this work
Jung-Chun Lin, e-mail: [email protected]
Keywords: alternative splicing, colorectal cancer, miR-92a, nPTB, RBM4
Received: July 14, 2015 Accepted: October 06, 2015 Published: October 19, 2015
Dysregulated splicing of pre-messenger (m)RNA is considered a molecular occasion of carcinogenesis. However, the underlying mechanism is complex and remains to be investigated. Herein, we report that the upregulated miR-92a reduced the RNA-binding motif 4 (RBM4) protein expression, leading to the imbalanced expression of the neuronal polypyrimidine tract-binding (nPTB) protein through alternative splicing-coupled nonsense mediated decay (NMD) mechanism. Increase in nPTB protein enhances the relative level of fibroblast growth factor receptor 2 IIIc (FGFR2) and pyruvate kinase M2 (PKM2) transcripts which contribute to the progression and metabolic signature of CRC cells. Expression profiles of RBM4 and downstream alternative splicing events are consistently observed in cancerous tissues compared to adjacent normal tissues. These results constitute a mechanistic understanding of RBM4 on repressing the carcinogenesis of colorectal cells.
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