The impact of RNA binding motif protein 4-regulated splicing cascade on the progression and metabolism of colorectal cancer cells.
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.
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Yu-Chih
YC
Liang
Division of Thoracic Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Wei-Cheng
WC
Lin
School of Chinese Medicine, China Medical University, Taichung, Taiwan.
Ying-Ju
YJ
Lin
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Jung-Chun
JC
Lin
D017398:Alternative Splicing / Q000235:genetics*; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D019069:Cell Respiration; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D024202:Electrophoretic Mobility Shift Assay; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D059365:Nonsense Mediated mRNA Decay; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000378:metabolism; D011770:Pyruvate Kinase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D034441:Heterogeneous-Nuclear Ribonucleoproteins; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; C450006:PTBP1 protein, human; C473692:RBM4 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D038941:Polypyrimidine Tract-Binding Protein; D011770:Pyruvate Kinase; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2
RBM4; alternative splicing; colorectal cancer; miR-92a; nPTB