Klin Onkol 2021; 34(1): 20-25. DOI: 10.48095/ccko202120.
Background: MicroRNA (miRNA) are a class of short non-coding RNAs that regulate gene expression at the posttranscriptional level. They are involved in key cellular processes and development as well as progression of many diseases. Their levels reflect the physiological state of organisms; therefore, the expression profiles of these molecules are analyzed in biomarker studies. Due to their properties, miRNA appear to be promising diagnostic, prognostic and predictive biomarkers of cancer. Recent studies indicate the existence of sequence variants in miRNA, so-called isomiRs, which differ from the annotated miRNAs by altered sequences due to posttranscriptional modifications. These isomiRs may have a higher abundance than canonical miRNA. The characterization of isomiRs reveals their regulated distribution and different biological properties and thus suggest the possible biological significance of the modifications. The presence of isomiRs can also significantly affect the results of biomarker studies. Currently, the research is focused on their possible clinical significance. Purpose: The aim of this review is to provide an overview of current knowledge about sequence variants in miRNA. The review summarizes the mechanisms of isomiRs biogenesis and describes the effects of sequence heterogeneity on miRNA stability, function and analysis. Subsequently, the role of isomiRs in biomarker studies is discussed.