Trash or Treasure: extracellular microRNAs and cell-to-cell communication

Abstract

Circulating RNAs in human body fluids are promising candidates for diagnostic purposes. However, the biological significance of circulating RNAs remains elusive. Recently, small non-coding RNAs, microRNAs (miRNAs), were isolated from multiple human body fluids, and these “circulating miRNAs” have been implicated as novel disease biomarkers. Concurrently, miRNAs were also identified in the extracellular space associated with extracellular vesicles (EVs), which are small membrane vesicles secreted from various types of cells. The function of these secreted miRNAs has been revealed in several papers. Circulating miRNAs have been experimentally found to be associated with EVs; however, other types of extracellular miRNAs were also described. This review discusses studies related to extracellular miRNAs, including circulating miRNAs and secreted miRNAs, to highlight the importance of studying not only secreted miRNAs, but also circulating miRNAs to determine the contribution of extracellular miRNAs especially in cancer development.

Identification of Double-stranded Genomic DNA Spanning All Chromosomes with Mutated KRAS and p53 DNA in the Serum Exosomes of Patients with Pancreatic Cancer

“…Because tumor-derived exosomes contain a wide range of RNA molecules and proteins, they have been considered to be promising candidates for discovery of diagnostic biomarkers in cancer and other diseases (1,20). However, the presence of DNA in exosomes is largely undetermined (21).…”

Circulating microRNA signature of genotype‐by‐age interactions in the long‐lived Ames dwarf mouse

“…There is evidence implicating these derivatives of sncRNAs in cell‐to‐cell communication both in normal biology and in disease states (Cortez et al ., 2011; Hoy & Buck, 2012; Shah & Calin, 2012; Turchinovich et al ., 2012; Kosaka et al ., 2013). Our deep sequencing studies of serum/plasma have consistently detected tRNA‐derived RNAs of size 30–33 nt (Dhahbi et al ., 2013a,b).…”

Small but mighty: microRNAs as novel signalling molecules in cancer

“…miRNAs secreted in EVs have been shown to travel stably over long distances in the body [4,21] . Recent evidence suggests that precursor miRNAs are packaged in exosomes with components of the RISC-loading complex (i.e., Dicer, AGO2, and TRBP) and are processed into mature miRNAs en route to their recipient target cells [82] .…”

“…As the physiological contributions of miRNAs have been elucidated, it has become increasingly evident that dysregulation of miRNA expression and secretion may promote pathological outcomes [4,20,21] . Aberrations in levels of specific, circulating miRNAs have been noted in association with acute myocardial infarction [22][23][24] , diabetes [25] , sepsis [26,27] , bipolar disorder [28] , and a wide range of cancers [29] .…”