A novel MIR100HG transcript enhances tumorigenesis by inducing BCLAF1-mediated alternative splicing in colorectal cancer
Abstract Background Long non-coding RNAs (lncRNAs) play crucial roles in cancer pathogenesis, including colorectal cancer (CRC). Distinct lncRNA transcripts from the same gene show diverse regulatory roles in cancer. The MIR100HG, a lncRNA gene characterized by multiple transcript variants, has been...
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| Format: | Article |
| Language: | English |
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BMC
2025-07-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02280-2 |
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| author | Mingrui Dai Yuhua Shi Hailin Zhao Yue Hu Xianling Cong Bin Yu Haihong Zhang Xianghui Yu Hui Wu |
| author_facet | Mingrui Dai Yuhua Shi Hailin Zhao Yue Hu Xianling Cong Bin Yu Haihong Zhang Xianghui Yu Hui Wu |
| author_sort | Mingrui Dai |
| collection | DOAJ |
| description | Abstract Background Long non-coding RNAs (lncRNAs) play crucial roles in cancer pathogenesis, including colorectal cancer (CRC). Distinct lncRNA transcripts from the same gene show diverse regulatory roles in cancer. The MIR100HG, a lncRNA gene characterized by multiple transcript variants, has been implicated in promoting CRC oncogenesis. However, the specific functions of individual MIR100HG transcripts in tumorigenesis remain unclear. Methods We explored the MIR100HG transcripts upregulated by TGFβ1 treated in CRC cells using RNA-Seq and characterized a novel transcript in CRC cells and tumor tissues via qRT-PCR. Chromatin immunoprecipitation and luciferase assays revealed this transcript’s upstream regulation. Functional experiments were performed in vitro and in mouse models. The molecular mechanism was elucidated through RNA-seq, RNA pull-down, mass spectrometry, RNA immunoprecipitation and co-immunoprecipitation. Finally, we evaluated the transcript’s therapeutic potential by treating mouse model tumors with antisense oligonucleotide. Results We identified a novel transcript, MIR100HG-L, which retains more portion of exon 1 compared to the previously reported shorter transcript. MIR100HG-L was transcriptionally upregulated by TGFβ/SMAD signaling and exhibited elevated expression in CRC tissues. Functionally, this transcript was demonstrated to promote CRC cell proliferation, suppress apoptosis and enhance drug resistance. Mechanistically, MIR100HG-L specifically interacted with BCLAF1, serving as a protein scaffold to connect BCLAF1 with splicing factors. This interaction significantly induced BCLAF1-mediated splicing events of oncogenes related to apoptosis and DNA damage response, enhancing their expression and contributing to CRC development. MIR100HG-L-targeted antisense therapy reduced tumor growth and increased cetuximab sensitivity. Conclusions Our study reveals a novel MIR100HG transcript induced by TGFβ/SMAD signaling and explores its distinct oncogenic mechanism through a structure-specific interaction with the BCLAF1. These findings suggest distinct MIR100HG transcripts may exert diverse functions and lead to the identification of novel molecular markers and therapeutic targets for CRC. |
| format | Article |
| id | doaj-art-87a6e91024ce4ef4a9d3ad246bd13fbd |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-87a6e91024ce4ef4a9d3ad246bd13fbd2025-08-20T04:03:07ZengBMCCell Communication and Signaling1478-811X2025-07-0123112010.1186/s12964-025-02280-2A novel MIR100HG transcript enhances tumorigenesis by inducing BCLAF1-mediated alternative splicing in colorectal cancerMingrui Dai0Yuhua Shi1Hailin Zhao2Yue Hu3Xianling Cong4Bin Yu5Haihong Zhang6Xianghui Yu7Hui Wu8National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin UniversityNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin UniversityNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin UniversityDepartment of Biobank, The China-Japan Union Hospital of Jilin UniversityDepartment of Biobank, The China-Japan Union Hospital of Jilin UniversityNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin UniversityNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin UniversityNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin UniversityNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin UniversityAbstract Background Long non-coding RNAs (lncRNAs) play crucial roles in cancer pathogenesis, including colorectal cancer (CRC). Distinct lncRNA transcripts from the same gene show diverse regulatory roles in cancer. The MIR100HG, a lncRNA gene characterized by multiple transcript variants, has been implicated in promoting CRC oncogenesis. However, the specific functions of individual MIR100HG transcripts in tumorigenesis remain unclear. Methods We explored the MIR100HG transcripts upregulated by TGFβ1 treated in CRC cells using RNA-Seq and characterized a novel transcript in CRC cells and tumor tissues via qRT-PCR. Chromatin immunoprecipitation and luciferase assays revealed this transcript’s upstream regulation. Functional experiments were performed in vitro and in mouse models. The molecular mechanism was elucidated through RNA-seq, RNA pull-down, mass spectrometry, RNA immunoprecipitation and co-immunoprecipitation. Finally, we evaluated the transcript’s therapeutic potential by treating mouse model tumors with antisense oligonucleotide. Results We identified a novel transcript, MIR100HG-L, which retains more portion of exon 1 compared to the previously reported shorter transcript. MIR100HG-L was transcriptionally upregulated by TGFβ/SMAD signaling and exhibited elevated expression in CRC tissues. Functionally, this transcript was demonstrated to promote CRC cell proliferation, suppress apoptosis and enhance drug resistance. Mechanistically, MIR100HG-L specifically interacted with BCLAF1, serving as a protein scaffold to connect BCLAF1 with splicing factors. This interaction significantly induced BCLAF1-mediated splicing events of oncogenes related to apoptosis and DNA damage response, enhancing their expression and contributing to CRC development. MIR100HG-L-targeted antisense therapy reduced tumor growth and increased cetuximab sensitivity. Conclusions Our study reveals a novel MIR100HG transcript induced by TGFβ/SMAD signaling and explores its distinct oncogenic mechanism through a structure-specific interaction with the BCLAF1. These findings suggest distinct MIR100HG transcripts may exert diverse functions and lead to the identification of novel molecular markers and therapeutic targets for CRC.https://doi.org/10.1186/s12964-025-02280-2Colorectal cancerLncRNAMIR100HGTranscriptTumorigenesisBCLAF1 |
| spellingShingle | Mingrui Dai Yuhua Shi Hailin Zhao Yue Hu Xianling Cong Bin Yu Haihong Zhang Xianghui Yu Hui Wu A novel MIR100HG transcript enhances tumorigenesis by inducing BCLAF1-mediated alternative splicing in colorectal cancer Cell Communication and Signaling Colorectal cancer LncRNA MIR100HG Transcript Tumorigenesis BCLAF1 |
| title | A novel MIR100HG transcript enhances tumorigenesis by inducing BCLAF1-mediated alternative splicing in colorectal cancer |
| title_full | A novel MIR100HG transcript enhances tumorigenesis by inducing BCLAF1-mediated alternative splicing in colorectal cancer |
| title_fullStr | A novel MIR100HG transcript enhances tumorigenesis by inducing BCLAF1-mediated alternative splicing in colorectal cancer |
| title_full_unstemmed | A novel MIR100HG transcript enhances tumorigenesis by inducing BCLAF1-mediated alternative splicing in colorectal cancer |
| title_short | A novel MIR100HG transcript enhances tumorigenesis by inducing BCLAF1-mediated alternative splicing in colorectal cancer |
| title_sort | novel mir100hg transcript enhances tumorigenesis by inducing bclaf1 mediated alternative splicing in colorectal cancer |
| topic | Colorectal cancer LncRNA MIR100HG Transcript Tumorigenesis BCLAF1 |
| url | https://doi.org/10.1186/s12964-025-02280-2 |
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