From “Junk DNA” to Clinically Relevant Tools for Cancer Diagnosis, Staging, and Tailored Therapies: The Incredible Case of Non-Coding RNAs

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Background

Today, it is widely demonstrated that protein-coding genes (~21,000) are significantly outnumbered by genomic sequences (the so-called “junk DNA”) that do not encode for proteins, but display critical role in several physiological and pathological processes such as differentiation, development, inflammation, immune response and cancer.

Initially considered as mere transcriptional noise, lacking a functional role in cell biology, non-coding RNAs (ncRNAs) include about 9,000 small (under 200bp) non-coding RNAs and more than 40,000 long (200bp-100kb) non-coding RNAs. Noteworthy, it has been demonstrated by comparative genome analysis that the evolution stage and degree of complexity of species correlate with the abundance of non-coding genes, more than protein-coding genes, clearly indicating the crucial importance of this part of the transcriptome. Although several studies in the last decade have already identified numerous molecular mechanisms through which ncRNAs exert their biological functions, new, unexpected discoveries in the field of the non-coding transcriptome are constantly reported.

Altered expression levels of non-coding RNAs have been identified in several human diseases, especially in different types of tumors. In cancer patients, specific “signatures” of ncRNAs can provide appropriate disease diagnosis, as well as prediction of clinical outcome and sensitivity or resistance to anti-neoplastic treatments. Notably, the technologies required for the proper identification and quantification of ncRNAs in cells, tissues and body fluid have become much easier and less expensive in the last years, paving the way for their potential routine use in the clinical practice.

On the other hand, a growing body of evidence demonstrates that ncRNAs are causally involved in cancer pathogenesis, and for this reason the modulation of non-coding transcriptome (i.e. recovering or abrogating the expression of tumor-suppressive or oncogenic ncRNAs, respectively) might represent a valuable approach for cancer treatment. However, the appropriate delivery of ncRNA-based therapeutics specifically to cancer cells represents one of the most critical challenges in this perspective.

This Research Topic aims to collect original research articles, reviews, mini-reviews, commentaries and opinions focused on the impact of non-coding RNAs, either as biomarkers predictive of clinical outcome and/or response to therapies, or as therapeutic agents. The main purpose is to provide the readers with state-of-the-art translational use of ncRNAs for the enhancement of current anti-neoplastic therapies and improvement of quality of life of cancer patients. Relevant topics include, but are not limited to:

• Novel techniques and assays for detection and quantification of ncRNAs
• Cancer-specific signatures of ncRNAs related to cancer cell sensitivity/resistance to therapies
• New approaches for the in vivo delivery of ncRNAs to cancer cells
• Mechanisms of modulation of ncRNA biogenesis

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Keywords: ncRNAs, cancer, resistance, sensitivity, biomarkers

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