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

Micro-RNAs, or miRNAs, are crucial post-transcriptional regulators of gene expression that significantly impact cancer progression and outcomes. Recent research suggests that RNA-binding proteins (RBPs) also play a significant role in post-transcriptional regulation of miRNA activity. By analyzing RNA-seq data from a wide range of RBP inhibition experiments, human cell lines, and tissues, researchers have compiled a map of regulatory connections between 34 RBPs and 28 miRNAs.

Additionally, a global analysis of miRNA abundance and activity in thousands of tumor and control samples from 17 human cancers reveals that RBP-driven regulation of miRNA activity is prevalent in tumors and contributes to the diversity in miRNA activity profiles. Specific RBPs that regulate the activity of both tumor-suppressor and oncogenic miRNAs, such as miR-29-3p, miR-17-5p, and miR-19-3p, have been identified.

DDX55, a pan-cancer negative regulator of the tumor-suppressor miR-29-3p family, has been particularly noteworthy.

Functional studies demonstrate that inhibiting DDX55 restores the gene-silencing activity of miR-29-3p and decreases cancer cell viability. This study marks the first pan-cancer investigation into the functional regulatory connections between RBPs and miRNAs, emphasizing the potential for targeting RBPs as a novel strategy to reprogram abnormal miRNA activities in cancer.