Systematical Analysis of Cutaneous Squamous Cell Carcinoma Network of microRNAs, Transcription Factors, and Target and Host Genes

Background: MicroRNAs (miRNAs) are small non-coding RNA molecules found in multicellular eukaryoteswhich are implicated in development of cancer, including cutaneous squamous cell carcinoma (cSCC). Expressionis controlled by transcription factors (TFs) that bind to specific DNA sequences, thereby controlling the flow(or transcription) of genetic information from DNA to messenger RNA. Interactions result in biological signalcontrol networks. Materials and
Methods: Molecular components involved in cSCC were here assembledat abnormally expressed, related and global levels. Networks at these three levels were constructed withcorresponding biological factors in term of interactions between miRNAs and target genes, TFs and miRNAs,and host genes and miRNAs. Up/down regulation or mutation of the factors were considered in the context ofthe regulation and significant patterns were extracted.
Results: Participants of the networks were evaluatedbased on their expression and regulation of other factors. Sub-networks with two core TFs, TP53 and EIF2C2,as the centers are identified. These share self-adapt feedback regulation in which a mutual restraint exists. Upor down regulation of certain genes and miRNAs are discussed. Some, for example the expression of MMP13,were in line with expectation while others, including FGFR3, need further investigation of their unexpectedbehavior.
Conclusions: The present research suggests that dozens of components, miRNAs, TFs, target genesand host genes included, unite as networks through their regulation to function systematically in human cSCC.Networks built under the currently available sources provide critical signal controlling pathways and frequentpatterns. Inappropriate controlling signal flow from abnormal expression of key TFs may push the system intoan incontrollable situation and therefore contributes to cSCC development.