Abstract
Simple SummaryCutaneous Squamous Cell Carcinoma is poorly understood at a molecular level, however emerging evidence have highlighted that non-coding RNAs play a key role in the oncogenesis and tumor progression. Herein we focused on the translational potential of non-coding RNAs, such as miRNAs, circular RNAs and lncRNAs, by reporting cutting edge findings showing that they can be considered as potential predictors of response to diverse class of drugs, including chemotherapeutics and immune checkpoints inhibitors and as reliable prognosticators. Additionally, by reporting the molecular mechanisms of drug sensitivity and resistance in which non-coding RNAs are involved, we highlighted their potential role as druggable targets and suggested new therapeutic options for CSCC patients.Cutaneous squamous cell carcinoma (CSCC) is the most common keratinocyte-derived skin cancer in the Caucasian population. Exposure to UV radiations (UVRs) represents the main risk carcinogenesis, causing a considerable accumulation of DNA damage in epidermal keratinocytes with an uncontrolled hyperproliferation and tumor development. The limited and rarely durable response of CSCC to the current therapeutic options has led researchers to look for new therapeutic strategies. Recently, the multi-omics approaches have contributed to the identification and prediction of the key role of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), circularRNAs (circRNAs) and long non-coding RNAs (lncRNAs) in the regulation of several cellular processes in different tumor types, including CSCC. ncRNAs can modulate transcriptional and post-transcriptional events by interacting either with each other or with DNA and proteins, such as transcription factors and RNA-binding proteins. In this review, the implication of ncRNAs in tumorigenesis and their potential role as diagnostic biomarkers and therapeutic targets in human CSCC are reported.
Highlights
Cutaneous squamous cell carcinoma (CSCC) is the most common non-melanoma skin cancer, accounting for about 20% of all cutaneous malignancies [1]
It has been found that PICSAR is involved in the regulation of different cell processes. It is well-known that UVA radiations play a key role in cutaneous carcinogenesis by promoting an over-activation of ERK1/2 signaling in keratinocytes [159], but UVA radiations are not the only factor implicated in MAPK/ERK pathway dysregulation in CSCC
Since this long non-coding RNAs (lncRNAs) has been shown to be down-regulated by cisplatin in the laryngeal squamous cell carcinoma model [160], it could be a promising predictor of response to platin-based chemotherapy in CSCC if the evidence reported by Chen is confirmed in this pathology, too [160]
Summary
Cutaneous squamous cell carcinoma (CSCC) is the most common non-melanoma skin cancer, accounting for about 20% of all cutaneous malignancies [1]. NcRNAs are involved in the initiation, progression, migration, invasion, and chemoresistance in different cancer types, including CSCC, and modulate the cellular responses by acting as pro- or anti-tumor factors [3,15,16,17,18,19]. Given their implication in tumor pathogenesis, the ncRNAs have been elected as potential biomarkers and therapeutic targets in human CSCC. We focus on the mutational landscape which drives the tumor transformation of healthy keratinocytes into CSCC cells, and we propose to explore the oncogenic and tumor suppressor role of ncRNAs in CSCC cancerogenesis
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