A novel MIR100HG transcript enhances tumorigenesis by inducing BCLAF1-mediated alternative splicing in colorectal cancer

Sep 23, 2026

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Background: Long non-coding RNAs (lncRNAs) influence colorectal cancer (CRC) development, yet the roles of individual MIR100HG transcripts remain unclear. Methods: TGFβ1-treated CRC cells were analyzed by RNA-Seq to define upregulated MIR100HG transcripts, followed by qRT-PCR validation and upstream regulation mapping with chromatin immunoprecipitation, luciferase assays, and mechanistic studies using multiple RNA–protein approaches. Results: A novel MIR100HG-L transcript increased under TGFβ/SMAD signaling, promoted proliferation, suppressed apoptosis, and raised drug resistance by interacting with BCLAF1 to drive oncogene splicing. Antisense therapy reduced tumor growth and increased cetuximab sensitivity. Conclusions: MIR100HG-L reveals a distinct TGFβ/SMAD-driven oncogenic mechanism and supports MIR100HG transcripts as CRC biomarkers and therapeutic targets.

LanguageEnglish

CategoryHealthcare

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Pages20

Reading Time50 min

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Abstract

Background

Methods

Results

Conclusions

Background

Dai etal. Cell Communication and Signaling (2025) 23:328 [https://doi.org/10.1186/s12964-025-02280-2](https://doi.org/10.1186/s12964-025-02280-2) Cell Communication and Signaling RESEARCH Open Access A novel MIR100HG transcript enhances tumorigenesis by inducing BCLAF1-mediated alternative splicing in colorectal cancer Mingrui Dai 1, Yuhua Shi 1,2, Hailin Zhao 1, Yue Hu3, Xianling Cong3, Bin Yu 1,2, Haihong Zhang 1,2, Xianghui Yu 1,2 and Hui Wu 1,2* 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 l ncRNA 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. Keywords Colorectal cancer, LncRNA, MIR100HG, Transcript, Tumorigenesis, BCLAF1 *Correspondence: Hui Wu [topwuhui@jlu.edu.cn](topwuhui@jlu.edu.cn) 1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin 130012, China 2Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Changchun, Jilin 130012, China 3Department of Biobank, The China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If m

FAQs

What is the main discovery about MIR100HG transcripts in colorectal cancer?

The study identifies a novel MIR100HG transcript, MIR100HG-L, which retains more of exon 1 than a previously reported shorter variant and is upregulated in CRC.

How does MIR100HG-L promote tumorigenesis at the molecular level?

MIR100HG-L specifically interacts with BCLAF1, acting as a protein scaffold to connect BCLAF1 with splicing factors and induce BCLAF1-mediated splicing of oncogenes involved in apoptosis and DNA damage response.

What therapeutic strategy did the study test, and what was the outcome?

The authors used antisense oligonucleotides targeting the transcript in mouse models, which reduced tumor growth and increased cetuximab sensitivity.

Sep 23, 2026

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