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

Abstract

Background: MicroRNAs (miRNAs) are small non-coding RNA molecules found in multicellular eukaryotes which are implicated in development of cancer, including cutaneous squamous cell carcinoma (cSCC). Expression is 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 signal control networks. Materials and Methods: Molecular components involved in cSCC were here assembled at abnormally expressed, related and global levels. Networks at these three levels were constructed with corresponding 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 of the regulation and significant patterns were extracted. Results: Participants of the networks were evaluated based 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. Up or 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 unexpected behavior. Conclusions: The present research suggests that dozens of components, miRNAs, TFs, target genes and 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 frequent patterns. Inappropriate controlling signal flow from abnormal expression of key TFs may push the system into an incontrollable situation and therefore contributes to cSCC development.

microRNAs are differentially regulated between MDM2-positive and negative malignant pleural mesothelioma

“…controlling oncogenic miR-128b. Of note, activation of TP53 leads to an genome-wide change of miRNA pattern, indicating that TP53 has a complex role in regulating miRNAs (Figure 4 ) [ 51 , 52 ].…”

Long non‐coding RNA SCARNA2 induces cutaneous squamous cell carcinoma progression via modulating miR‐342‐3p expression

“…cSCC is the second most frequent types of skin tumor and is responsible for 20% of skin cancer‐correlated mortalities every year 1–4 . CSCCs frequently occur on sun‐exposed positions of the body, including the lips, backs of the hands, ears and face 5–7 . cSCCs are usually correlated with high risk of metastasis and patients with metastatic cSCC have a poor survival 8–10 .…”