MicroRNA Regulation in Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (cSCC) arises from epidermal keratinocytes and ranks as the second most common skin cancer worldwide. MicroRNAs (miRNAs), a class of small non-coding RNAs, exert fine-tuned control over gene expression by binding target messenger RNAs and promoting their degradation or translational repression. In cSCC, dysregulation of specific miRNAs contributes to every stage of carcinogenesis, from early actinic keratosis to invasive disease. Some miRNAs act as onco-miRs, promoting proliferation, migration and angiogenesis by targeting tumour suppressor genes, while others function as tumour-suppressive miRNAs, restraining oncogenic pathways. Epigenetic changes such as promoter methylation can silence key miRNAs, shifting the balance towards malignant transformation. Functional studies in vitro and in vivo have revealed that perturbation of individual miRNAs can alter colony formation, tumour sphere growth and metastatic potential. Understanding the interplay between miRNA networks and core signalling cascades—such as MAPK, STAT3 and p53 pathways—offers opportunities for novel diagnostic biomarkers and miRNA-based therapeutics. Globally, elucidating miRNA regulation in cSCC promises to improve early detection, predict prognosis and guide targeted interventions in populations exposed to ultraviolet radiation and other risk factors.

Research from Nature Portfolio

Recent studies have identified the keratinocyte-specific miR-203 as a key regulator of epidermal homeostasis and a potential modulator of cSCC hyperproliferation. Transcriptome analyses in primary human keratinocytes overexpressing miR-203 revealed suppressed proliferation, mitosis and cell-cycle progression alongside activation of differentiation and apoptosis programmes. Among downregulated genes, SRC and RAPGEF1 emerged as direct targets, with their silencing recapitulating the antiproliferative effects of miR-203 in three-dimensional skin models. These findings highlight a mechanistic pathway by which miR-203 enforces differentiation, curbs oncogenic signalling and may be exploited to counteract keratinocyte transformation in the early stages of cSCC development.

MicroRNA Regulation in Cutaneous Squamous Cell Carcinoma publication trend

The graph below shows the total number of articles in microrna regulation in cutaneous squamous cell carcinoma across all publications each year (not limited to Nature Index journals).

Technical terms

MicroRNA (miRNA): Small non-coding RNA molecules (19–25 nucleotides) that regulate gene expression post-transcriptionally.

Keratinocyte: The predominant cell type in the epidermis responsible for barrier formation and renewal.

Onco-miR: A microRNA that promotes tumour development by downregulating tumour suppressor genes.

Tumour-suppressive miRNA: A microRNA that inhibits cancer progression by targeting oncogenes.

Antagomir: A synthetic oligonucleotide designed to bind and inhibit a specific microRNA.

Angiogenesis: Formation of new blood vessels, a process often co-opted by tumours to secure nutrient supply.

References

1. Knockdown of Simulated-Solar-Radiation-Sensitive miR-205-5p Does Not Induce Progression of Cutaneous Squamous Cell Carcinoma In Vitro. International Journal of Molecular Sciences (2023).
2. Identification and functional validation of SRC and RAPGEF1 as new direct targets of miR-203, involved in regulation of epidermal homeostasis. Scientific Reports (2023).
3. MicroRNA-23b Plays a Tumor-Suppressive Role in Cutaneous Squamous Cell Carcinoma and Targets Ras-Related Protein RRAS2. Journal of Investigative Dermatology (2023).
4. MiR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progression. Molecular Cancer (2016).
5. MicroRNA Dysregulation in Cutaneous Squamous Cell Carcinoma. International Journal of Molecular Sciences (2019).