A map of RBP-miRNA regulatory connections for deciphering the mechanisms of transcriptome remodeling in cancer

Abstract

Micro-RNAs (miRNAs) are key post-transcriptional regulators of gene expression that influence cancer progression and outcome. Whereas transcriptional dysregulation of miRNA abundance underlies abnormal functionality of some miRNAs in cancer, emerging data points to RNA-binding proteins (RBPs) as prominent post-transcriptional regulators of miRNA activity. Here, by modelling the regulon activities of well-characterized miRNA families in RNA-seq data of a comprehensive collection of RBP inhibition experiments, human cell lines and tissues, we report a map of regulatory connections between 34 RBPs and 28 miRNAs. Furthermore, through a global analysis of the abundance as well as the activity of miRNAs in thousands of tumor and control samples from 17 human cancers, we show that RBP-driven regulation of miRNA activity is common in tumors and contributes to the heterogeneity in miRNA activity profiles. We uncover a set of RBPs that regulate the activity of tumor-suppressor and oncogenic miRNAs, including miR-29-3p, miR-17-5p and miR-19-3p. Of particular interest, we describe a pan-cancer negative regulatory role for DDX55 on the activity of the miR-29-3p family, a critical miRNA family with tumor suppressor functions that is involved in most human cancers. Our functional studies confirm that DDX55 inhibition restores the gene-silencing activity of miR-29-3p and reduces cancer cell viability. Overall, our study provides the first pan-cancer investigation of functional regulatory connections between RBPs and miRNAs, and highlights RBPs whose interventional modulation may serve as a new approach to reprogram abnormal miRNA activities in cancer.

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BibTeX RIS

BibTeX

@misc{perron2026rbpmirna,
  title = {{A map of RBP-miRNA regulatory connections for deciphering the mechanisms of transcriptome remodeling in cancer}},
  author = {G. Perron and M. Amaravadi and H.-W. Tseng and P. Jandaghi and E. Moslemi and T. Nishimura and M. Rajaee and R. Alkallas and B. Culbertson and K. Garcia and I. R. Watson and H. Goodarzi and T. Duchaine and Y. Riazalhosseini and H. S. Najafabadi},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.29.755492},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.29.755492v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - A map of RBP-miRNA regulatory connections for deciphering the mechanisms of transcriptome remodeling in cancer
AU  - G. Perron
AU  - M. Amaravadi
AU  - H.-W. Tseng
AU  - P. Jandaghi
AU  - E. Moslemi
AU  - T. Nishimura
AU  - M. Rajaee
AU  - R. Alkallas
AU  - B. Culbertson
AU  - K. Garcia
AU  - I. R. Watson
AU  - H. Goodarzi
AU  - T. Duchaine
AU  - Y. Riazalhosseini
AU  - H. S. Najafabadi
PY  - 2026
DA  - 2026/09/29
PB  - bioRxiv
DO  - 10.64898/2026.09.29.755492
UR  - https://www.biorxiv.org/content/10.64898/2026.09.29.755492v1
AB  - Micro-RNAs (miRNAs) are key post-transcriptional regulators of gene expression that influence cancer progression and outcome. Whereas transcriptional dysregulation of miRNA abundance underlies abnormal functionality of some miRNAs in cancer, emerging data points to RNA-binding proteins (RBPs) as prominent post-transcriptional regulators of miRNA activity. Here, by modelling the regulon activities of well-characterized miRNA families in RNA-seq data of a comprehensive collection of RBP inhibition experiments, human cell lines and tissues, we report a map of regulatory connections between 34 RBPs and 28 miRNAs. Furthermore, through a global analysis of the abundance as well as the activity of miRNAs in thousands of tumor and control samples from 17 human cancers, we show that RBP-driven regulation of miRNA activity is common in tumors and contributes to the heterogeneity in miRNA activity profiles. We uncover a set of RBPs that regulate the activity of tumor-suppressor and oncogenic miRNAs, including miR-29-3p, miR-17-5p and miR-19-3p. Of particular interest, we describe a pan-cancer negative regulatory role for DDX55 on the activity of the miR-29-3p family, a critical miRNA family with tumor suppressor functions that is involved in most human cancers. Our functional studies confirm that DDX55 inhibition restores the gene-silencing activity of miR-29-3p and reduces cancer cell viability. Overall, our study provides the first pan-cancer investigation of functional regulatory connections between RBPs and miRNAs, and highlights RBPs whose interventional modulation may serve as a new approach to reprogram abnormal miRNA activities in cancer.
ER  -

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