MicroRNA Biogenesis and Cancer Pathways

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression post-transcriptionally by pairing with messenger RNAs and promoting their repression or degradation. Biogenesis begins with transcription of primary miRNA (pri-miRNA) transcripts, which are cleaved in the nucleus by the Drosha enzyme into precursor miRNA (pre-miRNA) hairpins. These are exported to the cytoplasm by Exportin-5 and further processed by the RNase III enzyme Dicer into mature miRNA duplexes. One strand of this duplex is loaded into the RNA-induced silencing complex (RISC), where Argonaute proteins guide it to complementary target sequences. Alterations in any of these steps can shift the balance between oncogenic and tumour-suppressive miRNAs, driving malignant transformation, progression and metastasis. Dysregulation may arise through genetic mutations or epigenetic changes in biogenesis factors and altered post-translational modification or localisation of key proteins. In many cancers, global miRNA expression is suppressed while specific oncomiRs are elevated, contributing to aberrant signalling through pathways such as TGF-β, PI3K and Wnt–β-catenin. Understanding these interconnected processes has revealed novel biomarkers and therapeutic targets with global relevance for precision oncology.

Research from Nature Portfolio

A study has identified a non-coding RNA, termed nc886, as a direct effector of TGF-β signalling in ovarian cancer. Elevated TGF-β induces nc886 expression, which binds to Dicer and inhibits its ability to process precursor miRNAs into mature forms. This blockade reproduces gene expression patterns characteristic of mesenchymal and fibrotic subtypes, enhancing cell adhesion, migratory and invasive behaviours, and conferring resistance to chemotherapeutic agents. The findings establish a molecular bridge between TGF-β signalling and miRNA biogenesis, highlighting nc886 as a potential prognostic marker and therapeutic target to restore miRNA-mediated repression in aggressive tumours.

MicroRNA Biogenesis and Cancer Pathways publication trend

The graph below shows the total number of articles in microrna biogenesis and cancer pathways across all publications each year (not limited to Nature Index journals).

Technical terms

Primary microRNA (pri-miRNA): The initial long transcript containing one or more miRNA hairpins cleaved by Drosha.

Precursor microRNA (pre-miRNA): A ∼70-nucleotide hairpin structure exported from the nucleus by Exportin-5.

Drosha: A nuclear RNase III enzyme that processes pri-miRNA into pre-miRNA.

Dicer: A cytoplasmic RNase III enzyme that cleaves pre-miRNA into a mature miRNA duplex.

Argonaute proteins (Ago): Core components of RISC that guide mature miRNAs to target mRNAs.

RNA-induced silencing complex (RISC): A multiprotein assembly that mediates miRNA-guided gene silencing.

References

1. The Role of Exportin-5 in MicroRNA Biogenesis and Cancer. Genomics Proteomics & Bioinformatics (2018).
2. nc886 is induced by TGF-β and suppresses the microRNA pathway in ovarian cancer. Nature Communications (2018).
3. Ago2/CAV1 interaction potentiates metastasis via controlling Ago2 localization and miRNA action. EMBO Reports (2024).
4. Understanding the Dosage-Dependent Role of Dicer1 in Thyroid Tumorigenesis. International Journal of Molecular Sciences (2024).
5. Pan-Cancer Study on Variants of Canonical miRNA Biogenesis Pathway Components: A Pooled Analysis. Cancers (2023).