The impact of extracellular vesicle-encapsulated circulating microRNAs in lung cancer research - PubMed (original) (raw)

Review

The impact of extracellular vesicle-encapsulated circulating microRNAs in lung cancer research

Yu Fujita et al. Biomed Res Int. 2014.

Abstract

Lung cancer is the leading cause of cancer-related deaths. Biomarkers for lung cancer have raised great expectations in their clinical applications for early diagnosis, survival, and therapeutic responses. MicroRNAs (miRNAs), a family of short endogenous noncoding RNAs, play critical roles in cell growth, differentiation, and the development of various types of cancers. Current studies have shown that miRNAs are present in the extracellular spaces, packaged into various membrane-bound vesicles. Tumor-specific circulating miRNAs have been developed as early diagnostic biomarkers for lung cancer. Remarkably, some studies have succeeded in discovering circulating miRNAs with prognostic or predictive significance. Extracellular vesicles (EVs), such as exosomes and microvesicles, are recognized as novel tools for cell-cell communication and as biomarkers for various diseases. Their vesicle composition and miRNA content have the ability to transfer biological information to recipient cells and play an important role in cancer metastasis and prognosis. This review provides an in-depth summary of current findings on circulating miRNAs in lung cancer patients used as diagnostic biomarkers. We also discuss the role of EV miRNAs in cell-cell communication and explore the effectiveness of these contents as predictive biomarkers for cancer malignancy.

PubMed Disclaimer

Figures

Figure 1

Figure 1

MiRNA release mechanisms into extracellular space. Precursor miRNAs are processed by ribonuclease Dicer to mature double-stranded miRNAs (miRNA duplex). One strand of the miRNA duplex is selectively loaded into the RNA-induced silencing complex (RISC), which contains the Argonaute (AGO) family protein as a core component. A fraction of miRNAs are released from living cells into the extracellular environment via the following mechanisms: (1) sorting into multivesicular bodies (MVB) and secretion via exosomes, (2) incorporating into microvesicles that are formed by the outward shedding of the plasma membrane, (3) associating with RNA-binding proteins, such as AGO2 and release of the miRNA-AGO complexes, and (4) exporting and incorporating into high-density lipoprotein (HDL) particles. Extracellular vesicle miRNAs are possibly involved in cell-cell communication.

Figure 2

Figure 2

Circulating microRNAs as a promising biomarker platform in lung cancer. Circulating miRNAs have been found to be packaged into various membrane-bound vesicles, such as exosomes and microvesicles and to exist in a vesicle-free form associated with protein or high-density lipoprotein complexes. Extracellular vesicles (EVs), such as exosomes and microvesicles, are recognized as novel tools for cell-cell communication and might be predictive biomarkers for cancer malignancy. EVs that circulate in body fluids can be readily recovered using several existing isolation methods and analyzed by various detection methods.

Similar articles

Cited by

References

    1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA: Cancer Journal for Clinicians. 2013;63(1):11–30. - PubMed
    1. Kosaka N, Iguchi H, Ochiya T. Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Science. 2010;101(10):2087–2092. - PMC - PubMed
    1. Baek D, Villén J, Shin C, Camargo FD, Gygi SP, Bartel DP. The impact of microRNAs on protein output. Nature. 2008;455(7209):64–71. - PMC - PubMed
    1. Cullen BR. Transcription and processing of human microRNA precursors. Molecular Cell. 2004;16(6):861–865. - PubMed
    1. Lee Y, Ahn C, Han J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003;425(6956):415–419. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources