| Autor: |
Yi-Su Chen, Chao-Wei Liu, Ying-Chin Lin, Chia-Ying Tsai, Ching-Hui Yang, Jung-Chun Lin |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Neoplasia: An International Journal for Oncology Research, Vol 22, Iss 12, Pp 702-713 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
1476-5586 |
| DOI: |
10.1016/j.neo.2020.10.002 |
| Popis: |
ABSTRACT: 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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