Non-Coding RNA Role in Cancer Biology

Non-coding RNAs (ncRNAs) have emerged as critical regulators in tumour initiation, progression and metastasis. Far from being transcriptional noise, distinct classes of ncRNAs—including microRNAs, long non-coding RNAs and circular RNAs—modulate gene expression at transcriptional, post-transcriptional and epigenetic levels. MicroRNAs fine-tune oncogene and tumour suppressor networks by directing mRNA degradation or translational repression. Long non-coding RNAs serve as scaffolds for chromatin-modifying complexes, decoys for transcription factors or guides for RNA-binding proteins, thereby influencing chromatin state and transcriptional programmes. Circular RNAs—formed by back-splicing of exons—exhibit exceptional stability and function as sponges for microRNAs or as platforms for protein interactions. Dysregulation of these molecules can alter cell cycle control, apoptosis, angiogenesis and immune surveillance. Moreover, ncRNA profiles have shown prognostic value and potential for therapeutic intervention, with synthetic mimics or inhibitors poised to reshape personalised oncology. The interplay among ncRNAs and coding transcripts underpins a complex regulatory layer that offers biomarker potential and novel drug targets.

Research from Nature Portfolio

Recent studies have uncovered the functional significance of circular RNAs in cancer cell proliferation and survival. An analysis of ribosomal-depleted transcriptomes across normal and malignant tissues revealed thousands of circular RNA species differentially expressed in tumours. One abundant molecule, derived from exon 2 of a kinase-interacting gene, was shown to promote growth by sequestering multiple microRNAs, including miR-124, thereby relieving repression of downstream oncogenic targets. Silencing of this circular RNA markedly inhibited tumour cell proliferation without affecting the linear host transcript, highlighting its independent regulatory role. These findings establish circular RNAs as key modulators of gene expression programmes in cancer and suggest avenues for therapeutic targeting of specific back-spliced isoforms.

Non-Coding RNA Role in Cancer Biology publication trend

The graph below shows the total number of articles in non-coding rna role in cancer biology across all publications each year (not limited to Nature Index journals).

Technical terms

MicroRNA (miRNA): Small (~22 nucleotides) non-coding RNAs that bind target messenger RNAs to inhibit translation or induce degradation.

Long non-coding RNA (lncRNA): Transcripts longer than 200 nucleotides that lack protein-coding potential and regulate gene expression via diverse mechanisms.

Circular RNA (circRNA): Covalently closed loop RNAs formed by back-splicing, resistant to exonuclease activity, often acting as microRNA sponges.

Competing endogenous RNA (ceRNA): RNAs that modulate each other’s levels by competing for shared miRNAs, influencing gene-regulatory networks.

Exosome: Small extracellular vesicles that transport proteins and RNAs between cells, mediating intercellular communication in the tumour microenvironment.

References

1. Exosome-derived circCCAR1 promotes CD8 + T-cell dysfunction and anti-PD1 resistance in hepatocellular carcinoma. Molecular Cancer (2023).
2. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nature Communications (2016).
3. The functional role of long non-coding RNA in human carcinomas. Molecular Cancer (2011).
4. CircRNA: functions and properties of a novel potential biomarker for cancer. Molecular Cancer (2017).