MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins

Vickers, Kasey C.; Palmisano, Brian T.; Shoucri, Bassem M.; Shamburek, Robert D.; Remaley, Alan T.

doi:10.1038/ncb2210

Cited by 2,417 publications

(2,362 citation statements)

References 62 publications

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“…Likewise, Scarb1 mutations in mice also resulted in increased HDL-C levels [38]. We have previously reported that HDL-delivery of miRNAs to hepatocytes in vitro requires SR-BI [13]. Based on these observations, we hypothesized that SR-BI may regulate sRNA levels on lipoproteins as well as miRNAs in liver and bile.…”

Section: Resultsmentioning

confidence: 99%

“…Currently, it is unknown if lipoproteins transport other sRNAs in addition to miRNAs. In a previous study, we reported that HDL transfer miRNAs to recipient cells and this process is regulated by HDL’s receptor, scavenger receptor BI (SR-BI), in hepatocytes [13]. SR-BI is a bidirectional transporter of cholesterol and a critical factor in reverse cholesterol transport pathway in which HDL returns excess cholesterol to the liver for excretion to bile.…”

Section: Introductionmentioning

confidence: 99%

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Bioinformatic analysis of endogenous and exogenous small RNAs on lipoproteins

Allen

Zhao

Solano

et al. 2018

J of Extracellular Vesicle

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To comprehensively study extracellular small RNAs (sRNA) by sequencing (sRNA-seq), we developed a novel pipeline to overcome current limitations in analysis entitled, “Tools for Integrative Genome analysis of Extracellular sRNAs (TIGER)”. To demonstrate the power of this tool, sRNA-seq was performed on mouse lipoproteins, bile, urine and livers. A key advance for the TIGER pipeline is the ability to analyse both host and non-host sRNAs at genomic, parent RNA and individual fragment levels. TIGER was able to identify approximately 60% of sRNAs on lipoproteins and >85% of sRNAs in liver, bile and urine, a significant advance compared to existing software. Moreover, TIGER facilitated the comparison of lipoprotein sRNA signatures to disparate sample types at each level using hierarchical clustering, correlations, beta-dispersions, principal coordinate analysis and permutational multivariate analysis of variance. TIGER analysis was also used to quantify distinct features of exRNAs, including 5ʹ miRNA variants, 3ʹ miRNA non-templated additions and parent RNA positional coverage. Results suggest that the majority of sRNAs on lipoproteins are non-host sRNAs derived from bacterial sources in the microbiome and environment, specifically rRNA-derived sRNAs from Proteobacteria. Collectively, TIGER facilitated novel discoveries of lipoprotein and biofluid sRNAs and has tremendous applicability for the field of extracellular RNA.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bioinformatic analysis of endogenous and exogenous small RNAs on lipoproteins

Allen

Zhao

Solano

et al. 2018

J of Extracellular Vesicle

Self Cite

View full text Add to dashboard Cite

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“…New studies have revealed that high‐density lipoproteins (HDL) and low‐density lipoproteins (LDL) can transport miRNAs into cells as well (Vickers et al ., 2011). In 2011, Vickers et al . demonstrated that several types of RNAs, such as miRNAs and tRNAs, could be detected in HDL and LDL particles.…”

Section: How Cells Communicatementioning

confidence: 99%

Cell‐to‐cell communication: microRNAs as hormones

2017

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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.

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“…Beside cellular miRNAs, it is well known that miRNAs can be released into the bloodstream and circulate within extracellular spaces [reviewed in Dhahbi (2014a)]. Some circulatory miRNAs may be packaged in lipid vesicles or complexed with high density lipoproteins particles or RNA‐binding proteins (Vickers et al ., 2011). …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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SummaryRecent evidence demonstrates that serum levels of specific miRNAs significantly change with age. The ability of circulating sncRNAs to act as signaling molecules and regulate a broad spectrum of cellular functions implicates them as key players in the aging process. To discover circulating sncRNAs that impact aging in the long‐lived Ames dwarf mice, we conducted deep sequencing of small RNAs extracted from serum of young and old mice. Our analysis showed genotype‐specific changes in the circulating levels of 21 miRNAs during aging [genotype‐by‐age interaction (GbA)]. Genotype‐by‐age miRNAs showed four distinct expression patterns and significant overtargeting of transcripts involved in age‐related processes. Functional enrichment analysis of putative and validated miRNA targets highlighted cellular processes such as tumor suppression, anti‐inflammatory response, and modulation of Wnt, insulin, mTOR, and MAPK signaling pathways, among others. The comparative analysis of circulating GbA miRNAs in Ames mice with circulating miRNAs modulated by calorie restriction (CR) in another long‐lived mouse suggests CR‐like and CR‐independent mechanisms contributing to longevity in the Ames mouse. In conclusion, we showed for the first time a signature of circulating miRNAs modulated by age in the long‐lived Ames mouse.

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MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins

Cited by 2,417 publications

References 62 publications

Bioinformatic analysis of endogenous and exogenous small RNAs on lipoproteins

Bioinformatic analysis of endogenous and exogenous small RNAs on lipoproteins

Cell‐to‐cell communication: microRNAs as hormones

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

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