miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Abstract

MicroRNAs (miRNAs) represent a class of small, non-coding RNAs with the main roles of regulating mRNA through its degradation and adjusting protein levels. In recent years, extraordinary progress has been made in terms of identifying the origin and exact functions of miRNA, focusing on their potential use in both the research and the clinical field. This review aims at improving the current understanding of these molecules and their applicability in the medical field. A thorough analysis of the literature consulting resources available in online databases such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate was performed. There is promising evidence that in spite of the lack of standardized protocols regarding the use of miRNAs in current clinical practice, they constitute a reliable tool for future use. These molecules meet most of the required criteria for being an ideal biomarker, such as accessibility, high specificity, and sensitivity. Despite present limitations, miRNAs as biomarkers for various conditions remain an impressive research field. As current techniques evolve, we anticipate that miRNAs will become a routine approach in the development of personalized patient profiles, thus permitting more specific therapeutic interventions.Biogenesis of miRNA begins in the nucleus, where the transcription of its precursor, primary miRNA or pri-miRNA takes place under the influence of RNA polymerases II and III [11,12]. The resulting molecule is a hairpin-like structure, which contains a loop at one end [11]. This primordial mi-RNA precursor that is usually made up of hundreds of nucleotides is then processed consecutively by two RNase III enzymes [13][14][15]. The first enzyme to act upon the pri-miRNA, which still resides in the nucleus, is called Drosha or DCGR8, and turns it into a new hairpin-like structure of approximately 70 nucleotides, the Precursor-miRNA or pre-miRNA. The latter is then transported to the cytoplasm, with the help of Exportin-5, where it is cleaved again by the Ago2/Dicer complex leading to the short, mature miRNA double strands [16].Further on, one of the strands, usually known as the guide strand, will be integrated into the RNA-induced silencing complex (RISC), while the other one, known as the passenger strand, is going to be degraded, even though in some occasions it has been found to be also functional [17]. In most cases, the strand that contains the less stable 5 end or a uracil at the beginning is more likely to be selected as the guide strand [18][19][20]. In those situations, where the passenger strand is not degraded and both get incorporated into the miRISC complex, the mature miRNA in the guide strand will be the dominant one [21,22].The main role of miRNA in the human body is gene regulation [23] by mediating the degradation of mRNA and also by regulating transcription and translation through canonical and non-canonical mechanisms [4]. The canonical mechanism means that the miRISC complex containing the miRNA guide strand is exerting its action by binding to the targ...

sTAM: An Online Tool for the Discovery of miRNA-set Level Disease Biomarkers

“…Recently, miRNAs have shown their excellent ability as biomarkers for various cancer and other diseases. 7,8 Given that lots of miRNAs were identified in a number of body fluids and miRNAs normally show high stability, 9,10 which makes them suitable to be biomarkers for many diseases.…”

“…miRNA set of size and single sample , of the dataset of miRNAs, the miRNAs are sorted according to their absolute expression values from high to low: = { 1 , 2 , … , }.An enrichment score ( , ) is obtained by a sum of the difference between a weighted8 Empirical Cumulative Distribution Functions (ECDF) of the miRNAs in the miRNA set and the ECDF of the remaining miRNAs :sTAM repeated this calculation for each miRNA set and each sample in the expression dataset.…”

Potential Diagnostic Value of Circulating miRNA for Multiple Myeloma: A Meta-Analysis.

“…Therefore, we need a more accurate and advanced noninvasive biomarker for the early diagnosis of MM. According to the latest research, miRNA had strong speci city and sensitivity in diagnosing the occurrence and metastasis of malignant tumors [13,38] , and can be used as a new method for early diagnosis and monitoring of tumors. Several studies had analyzed the accuracy of circulating miRNAs in diagnosing MM.…”

“…We found that downregulation of microRNA clusters with larger samples size of plasma type could carry out a better diagnostic accuracy of MM patients. The expression of a single miRNA in serum or plasma lacks speci city in cancer detection, and it might uctuate in other diseases [38] . However, miRNA clusters with complex molecular mechanisms can re ect the occurrence and development of tumors in many ways, forming a more stable and reliable network diagnostic structure [40] .…”

Circulating microRNAs in Early Breast Cancer Patients and Its Association With Lymph Node Metastases

“…Accumulating evidence in the last years has highlighted the potential use of peripheral blood circulating nucleic acids in breast cancer diagnosis, prognosis and for monitoring response to anticancer therapy. Among these, circulating microRNAs (miRNAs) are increasingly recognized as a promising noninvasive biomarker, given the ease with which miRNAs can be isolated and their structural stability under different conditions of sample processing and isolation (11)(12)(13).…”