MicroRNA signatures landscape in renal cell carcinoma – related epithelial to mesenchymal transition

Grigorios Theodoropoulos^1,*, Evangelos Tsiambas^2,6*, Paraskevi Tziakou³*, Despoina Spyropoulou⁴*, Athanasios Niotis⁵, Harikleia Gakiopoulou⁶, Odysseas Dimas⁷, Loukas Manaios⁸, Andreas C Lazaris⁶, Georgia Thomopoulou⁹

¹Department of Urology, “Elpis” General Hospital, Athens, Greece.

²Department of Cytology, 417 VA (NIMTS), Athens, Greece.

³Department of Pathology, “Thriasio” General Hospital, Elefsina, Greece.

⁴Department of Radiation Oncology, Medical School, University of Patras, Greece.

⁵Department of Surgery, 417 VA (NIMTS), Athens, Greece.

⁶Department of Pathology, Medical School, University of Athens, Greece.

⁷2nd Department of Internal Medicine, ‘’Gennimatas’’ General Hospital, Athens, Greece.

⁸Department of Surgery, Bioclinic Medical Center, Athens, Greece.

⁹Department of Cytopathology, University General Hospital “Attikon’’, Athens, Greece.

*These authors contributed equally to this work

Summary

Epithelial malignancies demonstrate aggressive phenotypes (increased metastatic potential) due to mechanisms including the epithelial-to-mesenchymal transition (EMT). Novel micro-epigenetic markers –the micro-RNAs (miRs) – are under investigation in solid malignancies for diagnostic, prognostic or specific targeted therapy purposes. miRs are considered very promising and significant genetic markers for categorizing patients by their molecular characteristics, extending also their complicated genetic signatures. miRs are short, non-coding RNAs consisting of 20-25 nucleotides located at intra- or inter-gene regions. Functional miRs mediate a positive regulation of posttranscriptional gene silencing. Their deregulation in cancer cells due to genetic (mutations, translocations), epigenetic (DNA hypermethylation of tumour suppressor genes, extensive genomic DNA hypomethylation, aberrant histone modification patterns) and transcriptional alterations leads to a loss of miRs-mediated repression of target mRNA. Interestingly, a biphasic role of miRs in cancers of different histogenetic origin has been confirmed. In some of them, their upregulation correlates with an increased ongogenic activity, whereas in others the same miR type acts as a suppressor agent. In the current special molecular review we describe specific miRs in EMT development and progression in renal cell carcinoma (RCC).

Key words: gene, renal cell carcinoma, microRNAs, epithelial-to-mesenchymal transition.

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