Cell‐to‐cell communication: microRNAs as hormones

Abstract

Mammalian cells can release different types of extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies. Accumulating evidence suggests that EVs play a role in cell‐to‐cell communication within the tumor microenvironment. EVs’ components, such as proteins, noncoding RNAs [microRNAs (miRNAs), and long noncoding RNAs (lncRNAs)], messenger RNAs (mRNAs), DNA, and lipids, can mediate paracrine signaling in the tumor microenvironment. Recently, miRNAs encapsulated in secreted EVs have been identified in the extracellular space. Mature miRNAs that participate in intercellular communication are released from most cells, often within EVs, and disseminate through the extracellular fluid to reach remote target cells, including tumor cells, whose phenotypes they can influence by regulating mRNA and protein expression either as tumor suppressors or as oncogenes, depending on their targets. In this review, we discuss the roles of miRNAs in intercellular communication, the biological function of extracellular miRNAs, and their potential applications for diagnosis and therapeutics. We will give examples of miRNAs that behave as hormones.

Endothelial microRNAs regulating the NF‐κB pathway and cell adhesion molecules during inflammation

“…Interestingly, elevating blood miR-122 level in rats reduced the expression of these genes and thus improved stroke outcomes (76). miRNAs can be secreted from cells in various forms: associated with RNA-binding proteins such as Ago2 and nucleophosmin, within HDL or LDL particles, and within microvesicles (MVs) including microparticles (MPs), exosomes, and apoptotic bodies (77). Circulating miRNAs can be used as biomarkers for inflammatory and cardiovascular diseases.…”

miR‐155 overexpression is followed by downregulation of its target gene, NFE2L2, and altered pattern of VEGFA expression in the liver of melanoma B16‐bearing mice at the premetastatic stage

“…TDEs contain various components, including microRNAs, and can regulate intercellular communication in premetastatic sites . MicroRNAs can be delivered into cells within microvesicles, apoptotic bodies, lipoproteins and ribonucleoproteins . Thus, microRNAs may play a pivotal role in the regulation of metastasis formation; however, the exact mechanism underlying the role of microRNAs in melanoma progression remains unclear.…”

The 14q32.31DLK1-DIO3 MIR300 tumor suppressorpromotes leukemogenesis by inducing cancer stem cell quiescence and inhibiting NK cell anti-cancer immunity

“…Gain or loss of miRNA expression/function is a feature of cancer cells including CSCs 4,5 in which they may function as oncogenes or tumor suppressors influencing CSC's function, tumor growth and innate anti-cancer immunity 6,7 . Several miRNAs have been associated with CSC expansion and maintenance 4 and PP2A inactivation 8 ; however, a clear causal link between expression of specific miRNAs, persistence of the drug-resistant quiescent CSCs and PP2A loss-of-function is still missing.…”

“…oxygen tension), cell-to-cell direct and, soluble and/or exosome-encapsulated factor (e.g. miRNAs, TGFb1)-mediated interactions between tumor, mesenchymal stromal (MSCs), endothelial (EC) and immune cells 6,[13][14][15] .…”

“…By using Philadelphia-positive (Ph + ) chronic myelogenous leukemia (CML) in chronic (CP) and blastic (BC) phase, and complex karyotype (CK) acute myeloid leukemia (AML), as paradigmatic examples of stem cell-derived neoplasms characterized by constitutive expression of oncogenic kinases (e.g. BCR-ABL1, JAK2), PP2A loss-of-function, altered miRNA expression and, impaired NK cell proliferation and cytotoxicity 2,6,[23][24][25][26][27] , we show that MIR300 is a BMM (hypoxia, MSC)induced PP2A activator with cell context-independent tumor suppressor anti-proliferative and proapoptotic activities which are essential for induction and maintenance of LSC quiescence and impaired NK cell immunity but can also be exploited to selectively and efficiently induce cell death in qLSC and leukemic progenitor while sparing normal hematopoiesis.…”