Non-coding RNAs (ncRNAs) are RNA molecules without protein translation potential, but capable of modulating gene expression through different mechanisms. NcRNA-mediated gene silencing constitutes an important type of epigenetic alterations and has been implicated in several human carcinogenesis. An increasing number of studies have uncovered associations between ncRNAs and cancer predisposition or status during the last decade, opening a new avenue of work for the control of this disease. Among the different types of RNA molecules that fall under the term ncRNA, long-chain non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have attracted the most attention from the scientific community.
The lncRNA include all ncRNAs longer than 200 nucleotides in length and are therefore a very heterogeneous group of molecules that exhibit different biological functions capable of interacting with other RNAs and proteins. Depending on their subcellular localization, in the nucleus or cytoplasm, lncRNAs can interfere with transcriptional and post-transcriptional gene regulation, as well as with the translation of messenger RNA, respectively.
It has been shown that lncRNAs can be detected in some extracellular body fluids such as plasma or urine and show dynamic alteration in disease. lncRNAs can enter the bloodstream encapsulated in exosomes and extracellular vesicles or within apoptotic bodies released by dying cells. Their association with RNA-binding proteins explains their greater stability and resistance to degradation by RNAases. Therefore, their stability in the main body fluids used in laboratory diagnostic techniques (plasma and urine), together with the disease-specific abundance patterns, mean that lncRNAs are attracting enormous interest as a new class of non-invasive diagnostic and prognostic biomarkers.
In the specific case of cancer, advances in the understanding of lncRNA expression profiles have highlighted their potential value as tumor biomarkers in patient diagnosis and prognosis. Several studies have shown that lncRNAs play an important role in the regulation of gene expression at various levels, including chromatin modification, transcription and post-transcriptional processing. In addition, lncRNAs have been found to have oncogenic and tumor suppressor functions. In particular, the levels of several lncRNAs correlate with stage according to the TNM system, which takes into account tumor size, lymph node involvement and the existence of distant metastases. These data indicate that lncRNAs could offer clinical applications of great interest offering improvements not only at the diagnostic and prognostic level, but also emerging as new specific therapeutic targets.
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