Influence of a high-altitude hypoxic environment on human plasma microRNA profiles

Yan, Yan; Shi, Yonghui; Wang, Cheng; Guo, Peng-Tao; Wang, Junjun; Zhang, Chenyu

doi:10.1038/srep15156

Cited by 36 publications

(45 citation statements)

References 36 publications

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“…To systematically characterize the serum miRNA expression profile for mTBI patients and sTBI patients, we extracted total RNA from 100 µL serum with a 1‐step phenol/chloroform purification according to a previously described protocol (Yan et al ). The resulting RNA pellet was dissolved in 20 µL diethyl pyrocarbonate water and stored at −80°C until further analysis.…”

Section: Methodsmentioning

confidence: 99%

Screening the expression of several miRNAs from TaqMan Low Density Array in traumatic brain injury: miR‐219a‐5p regulates neuronal apoptosis by modulating CCNA2 and CACUL1

Yan

et al. 2019

Journal of Neurochemistry

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Circulating microRNAs (miRNAs) have emerged as diagnostic and prognostic biomarkers for traumatic brain injury (TBI). However, a comprehensive characterization of the serum miRNA profile in patients with TBI and the roles of these potential markers in neuronal regulation have rarely been reported. In this study, the levels of 754 serum miRNAs were initially determined in two pooled samples of 15 severe traumatic brain injury (sTBI) patients and 15 healthy controls using a TaqMan Low Density Array. The markedly upregulated miRNAs in sTBI patients were subsequently validated individually by quantitative reverse-transcription PCR (RT-qPCR) in another larger cohort consisting of 81 sTBI patients, 81 mild traumatic brain injury (mTBI) patients and 82 age/sex-matched healthy controls. Seven miRNAs, including miR-103a-3p, miR-219a-5p, miR-302d-3p, miR-422a, miR-518f-3p, miR-520d-3p and miR-627, were significantly upregulated in both sTBI and mTBI patients compared with their expression in controls. Among these miRNAs, miR-219a-5p not only discriminated sTBI and mTBI patients from controls but also discriminated between sTBI and mTBI patients. We further show here that in the neuronal cell injury model, upregulated miR-219a-5p inhibits the expression of CCNA2 and CACUL1 and further regulates akt/Foxo3a and p53/Bcl-2 signaling pathways, causing a notable change in the expression of cleaved caspase-3, thereby inducing neuronal apoptosis. These results indicate that these seven selected miRNAs could serve as novel biomarkers for TBI. In particular, miR-219a-5p is a potentially valuable indicator of the diagnosis, prognosis of TBI and appears to regulate neuronal apoptosis and death. Keywords: biomarker, CACUL1, CCNA2, microRNA, miR-219a-5p, traumatic brain injury.

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Section: Methodsmentioning

confidence: 99%

Screening the expression of several miRNAs from TaqMan Low Density Array in traumatic brain injury: miR‐219a‐5p regulates neuronal apoptosis by modulating CCNA2 and CACUL1

Yan

et al. 2019

Journal of Neurochemistry

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“…To control the variability in RNA extraction and puri cation procedures, an exogenous plant small molecular RNA named MIR2911 (5'-GGCCGGGGGACGGGCUGGGA-3'), was spiked into each sample with a nal concentration of 10 6 fmol/L during RNA isolation as a synthetic external reference for the normalization of serum miRNAs [18]. Hydrolysis probe-based quantitative reverse transcription polymerase chain reaction (RT-qPCR) was carried out using a TaqMan miRNA PCR kit (Applied Biosystems, Foster City, CA, USA) according to the manufacturer's instructions with a minor modi cation as previously described [18]. Brie y, 2 µL of total RNA was reverse transcribed to cDNA using AMV reverse transcriptase (TaKaRa, Dalian, China) and the stem-loop RT primer (Applied Biosystems, Foster City, CA, USA).…”

Section: Serum Rna Isolation and Rt-qpcr Assaymentioning

confidence: 99%

Different Expression Pattern of Human Cytomegalovirus-Encoded microRNAs in Circulation from Virus Latency to Reactivation

Zhou

Wang

Ding

et al. 2020

Preprint

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Background: Human cytomegalovirus (HCMV) is a beta-hersvirinae that has a high latent infection rate worldwide and can cause serious consequences in immunocompromised patients when reactivation; however, the mechanism of how HCMV convert from latent to reactivation has rarely been investigated. In the present study, we aimed to perform a comprehensive analysis of the HCMV-encoded microRNA (miRNA) profile in serum of patients upon HCMV reactivation from latency and to further evaluate its clinical significance for the disease monitoring and preventing usefulness.Methods: Serum samples from 60 viremia patients and 60 age-gender matched controls were enrolled in this study for screening and validation of different expression of HCMV miRNAs. Serum concentrations of 22 known HCMV miRNAs were determined by a hydrolysis probe-based stem-loop quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay. HCMV DNA was measured by quantitative real-time PCR (qPCR) with the whole blood sample. Serum HCMV IgG and IgM were assessed using enzyme linked immunosorbent assay (ELISA). Another 47 samples from 5 patients at different time points were collected to evaluate the monitoring effectiveness and disease prediction ability of differential expression HCMV-miRNAs during the antiviral treatment. Results: The RT-qPCR analysis revealed that the serum levels of 16 of the 22 examined HCMV miRNAs were elevated in HCMV viremia patients compared with controls, and a profile of 8 HCMV miRNAs including hcmv-miR-US25-2-3p, hcmv-miR-US4-5p, hcmv-miR-US25-2-5p, hcmv-miR-US25-1-3p, hcmv-miR-US25-1, hcmv-miR-UL36, hcmv-miR-UL148D, hcmv-miR-US29-3p were markedly elevated (fold change > 2, P < 0.01). Receiver operating characteristic curve (ROC) analysis were performed on the selected HCMV-miRNAs in all of the patients and controls that enrolled in this study, and which ranged from 0.74 to 0.79 in the autoimmune patients. In addition, hcmv-miR-US25-1-3p levels were significantly correlated with HCMV DNA copies (r = 0.297，P = 0.022), and were obviously higher in the reactivation set than the latency set in the autoimmune patients, which could be a predictor for the monitoring of the antiviral treatment.Conclusions: HCMV miRNAs profile showed markedly shift-switch from latency to reactivation in circulation from HCMV infected patients and hcmv-miR-US25-1-3p may be served as a predictor for the switch upon reactivation from latency in patients suffered with autoimmune diseases.

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“…Hsa-miR-210-3p (also known as the master regulator hypoxiamiR) expression is positively correlated with the change in red blood cell counts, haemoglobin and haematocrit values at HA and is proposed to be associated with human acclimatization to life at HA (9). Human plasma miRNA expression profiles are thus reported to be associated with human adaptation to hypobaric hypoxic environments (10). hsa-miR-369-3p, hsa-miR-449b-3p, and hsa-miR-136-3p, miR-495 and miR-323a-3p, miR-500a-5p and miR-501-5p have been reported to be differentially expressed at different altitude and duration of exposure and have been proposed to have immense potential as markers or therapeutic targets (11).…”

Section: Introductionmentioning

confidence: 99%

HAHmiR.DB: A Server Platform For High Altitude Human miRNA-Gene Coregulatory Networks And Associated Regulatory-Circuits

Khurana

Gupta

Sugadev

et al. 2020

Preprint

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Rapid ascent to High Altitude (HA) can cause severe damage to body organs and may lead to many fatal disorders. During induction to HA, human body undergoes various physiological, biochemical, hematological and molecular changes to adapt to the extreme environmental conditions. Many literature references hint that gene-expression-regulation and regulatory molecules like microRNAs (miRNAs) and Transcription Factors (TFs) control adaptive responses during HA-stress. These biomolecules are known to interact in a complex combinatorial manner to fine-tune the gene expression and help in controlling the molecular responses during this stress and ultimately help in acclimatization. HAHmiR.DB (High-Altitude Human miRNA Database) is a unique, comprehensive, curated collection of miRNAs that have been experimentally validated to be associated with HA-stress; their level of expression in different altitudes, fold change, experiment duration, biomarker association, disease and drug association, tissue-specific expression level, Gene Ontology (GO) and Kyoto Encyclopaedia of Gene and Genomes (KEGG) pathway associations. As a server platform it also uniquely constructs and analyses interactive miRNA-TF-Gene coregulatory networks and extracts regulatory-circuits/Feed Forward Loops (FFLs) using in-house scripts. These regulatory circuits help to offer mechanistic insights in complex regulatory mechanisms during HA stress. The server can also build these regulatory networks between two and more miRNAs of the database and also identify the regulatory-circuits from this network. Hence HAHmiR.DB is the first-of its-kind database in HA research which a reliable platform to explore, compare, analyse and retrieve miRNAs associated with HA stress, their coregulatory networks and FFL regulatory circuits. HAHmiR.DB is freely accessible at http://www.hahmirdb.in

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Influence of a high-altitude hypoxic environment on human plasma microRNA profiles

Cited by 36 publications

References 36 publications

Screening the expression of several miRNAs from TaqMan Low Density Array in traumatic brain injury: miR‐219a‐5p regulates neuronal apoptosis by modulating CCNA2 and CACUL1

Screening the expression of several miRNAs from TaqMan Low Density Array in traumatic brain injury: miR‐219a‐5p regulates neuronal apoptosis by modulating CCNA2 and CACUL1

Different Expression Pattern of Human Cytomegalovirus-Encoded microRNAs in Circulation from Virus Latency to Reactivation

HAHmiR.DB: A Server Platform For High Altitude Human miRNA-Gene Coregulatory Networks And Associated Regulatory-Circuits

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