The SRSF3-MBNL1-Acin1 circuit constitutes an emerging axis to lessen DNA fragmentation in colorectal cancer via an alternative splicing mechanism

Yi Su Chen, Chao Wei Liu, Ying Chin Lin, Chia Ying Tsai, Ching Hui Yang, Jung Chun Lin

研究成果: 雜誌貢獻文章同行評審

1 引文 斯高帕斯(Scopus)

摘要

Altered alternative splicing (AS) events are considered pervasive causes that result in the development of carcinogenesis. Herein, we identified reprogrammed expression and splicing profiles of Muscle blind-like protein 1 (MBNL1) transcripts in tumorous tissues compared to those of adjacent normal tissues dissected from individual colorectal cancer (CRC) patients using whole-transcriptome analyses. MBNL1 transcript 8 (MBNL18) containing exons 5 and 7 was majorly generated by cancerous tissues and CRC-derived cell lines compared with those of the normal counterparts. Interplay between the exonic CA-rich element and upregulated SRSF3 facilitated the inclusion of MBNL1 exons 5 and 7, which encode a bipartite nuclear localization signal (NLS) and conformational NLS. Moreover, abundant SRSF3 interfered with the autoregulatory mechanism involved in utilization of MBNL1 exons 5 and 7, resulting in enrichment of the MBNL18 isoform in cultured CRC cell lines. Subsequently, an increase in the MBNL18 isoform drove a shift in the apoptotic chromatin condensation inducer in nucleus 1-S (Acin1-S) isoform to the Acin1-L isoform, leading to diminished DNA fragmentation in cultured CRC cells under oxidative stress. Taken together, SRSF3-MBNL1-Acin1 was demonstrated to constitute an emerging axis which is relevant to proapoptotic signatures and post-transcriptional events of CRC cells.

原文英語
頁(從 - 到)702-713
頁數12
期刊Neoplasia (United States)
22
發行號12
DOIs
出版狀態已發佈 - 十二月 2020

ASJC Scopus subject areas

  • 癌症研究

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