The knowledge and understanding of the biology and immunology of Merkel cell carcinoma (MCC), a highly aggressive skin cancer with neuroendocrine features, expanded dramatically over the past decade, allowing new therapeutic interventions for this previously untreatable cancer. Merkel cell polyomavirus (MCPyV) seems to be the major causal factor for MCC since, approximately 80% of all MCC cases, are positive for viral DNAs (MCPyV+). UV exposure, together with immune deficiencies, fair skin, age (immune senescence), association with other cancer, and chronic inflammation, is considered the predominant etiological factor for MCPyV-negative (MCPyV-) MCCs.
In line with this distinction, it has been reported that MCPyV+ and MCPyV¿ MCCs are characterized by different clinical and molecular features including the ability to express microRNAs (miRNAs). In this manner, MCPyV+ and MCPyV- MCCs can create their own miRNAs molecular profile. miRNAs are small single-stranded non-coding RNAs of 18-25 nucleotides implicated in various human diseases such as skin cancers, including melanoma, squamous cell carcinoma, and basal cell carcinoma influencing post-transcriptionally regulate gene expression, tumor initiation, development progression, and aggressiveness.
Although the involvement of miRNAs in pathological processes has made them to be recognized as future biomarkers with diagnostic and/or prognostic potential, the expression of miRNAs and their biological relevance in MCC remains to be explored in depth. In order to set out to close this knowledge gap and define the microRNAs involved in MCC biology, the present project aims to study the expression of miRNAs in MCC tumors. Further purposes will be to compare the miRNA profiles with respect to MCPyV status (MCPyV - or MCPyV + MCCs), to find distinctions in miRNA expression and validate their role as potential biomarkers for the diagnosis, progression, prognosis, and therapeutic targets of MCCs.
MCC, with their steadily increasing incidence and mortality rate, need constant attention regarding the discovery of molecular mechanisms that govern tumorigenesis, metastasis, therapy resistance, and, last but not least, the development of new therapeutic strategies.
In the molecular events that characterize these complex processes, miRNAs, are recently gaining increased importance. However, as outlined above, the involvement of miRNAs in MCC is less characterized and, to date, obtained results are conflicting.
Since MCC-specific miRNAs as biomarkers still have a long way to go, this research could contribute to set out to close this knowledge gap and define:
- The intracellular microRNAome profile that allow to discriminate between MCPyV- and MCPyV+ MCCs.
- The functions of miRNAs as therapeutic targets. Since most of the currently reported miRNAs in MCC have dual functions, tumor-promoting and tumor-inhibiting properties in other cell systems, target their expression in course of biological therapies, may be a double-edged sword. Determine the contributing role of miRNAs in MCC oncogenesis is mandatory to design efficient and specific therapies.
To date, miRNAs have gained a role in the armamentarium of biomolecules regarded as disease markers. Achieve the results of this study would mean ascribe to MCC-specific miRNAs the role of biomarkers for the diagnosis, prognosis, progression and therapeutic targets of this cancer.