An in silico analysis of microRNAs: Mining the miRNAome

Murray, B. Stuart; Choe, Sung; Woods, Matthew; Ryan, Terence E.; Liu, Wei

doi:10.1039/c003961f

Cited by 39 publications

(23 citation statements)

References 55 publications

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“…We also examined two microRNAs, miR-92b and miR-93 that are highly expressed in hESCs. The miRNA miR-92b has been shown to target P57 for degradation and augment PRMT5 translation [15, 19], whereas miR-93 targets is predicted to target P57 mRNA for degradation together with P21 , TP53INP1 [20–22]. Our microarray reveals that both P57 and TP53INP 1 were de-repressed in PRMT5 KD cells.…”

Section: Resultsmentioning

confidence: 89%

PRMT5 is Required for Human Embryonic Stem Cell Proliferation But Not Pluripotency

Gkountela

Chin

Lee

et al. 2014

Stem Cell Rev and Rep

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Summary Human pluripotent stem cells (PSCs) are critical in vitro tools for understanding mechanisms that regulate lineage differentiation in the human embryo as well as a potentially unlimited supply of stem cells for regenerative medicine. Pluripotent human and mouse embryonic stem cells (ESCs) derived from the inner cell mass of blastocysts share a similar transcription factor network to maintain pluripotency and self-renewal, yet there are considerable molecular differences reflecting the diverse environments in which mouse and human ESCs are derived. In the current study we evaluated the role of Protein arginine methyltransferase 5 (PRMT5) in human ESC (hESC) self-renewal and pluripotency given its critical role in safeguarding mouse ESC pluripotency. Unlike the mouse, we discovered that PRMT5 has no role in hESC pluripotency. Using microarray analysis we discovered that a significant depletion in PRMT5 RNA and protein from hESCs changed the expression of only 78 genes, with the majority being repressed. Functionally, we discovered that depletion of PRMT5 had no effect on expression of OCT4, NANOG or SOX2, and did not prevent teratoma formation. Instead, we show that PRMT5 functions in hESCs to regulate proliferation in the self-renewing state by regulating the fraction of cells in Gap 1 (G1) of the cell cycle and increasing expression of the G1 cell cycle inhibitor P57. Taken together our data unveils a distinct role for PRMT5 in hESCs and identifies P57 as new target.

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Section: Resultsmentioning

confidence: 89%

PRMT5 is Required for Human Embryonic Stem Cell Proliferation But Not Pluripotency

Gkountela

Chin

Lee

et al. 2014

Stem Cell Rev and Rep

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“…Text mining of the existing miRNA literature [22] combined with the wealth of existing information on gene function was used to predict biological outcomes due to our observed miRNA changes. By text mining PubMed we could identify publications citing 61 of the 63-set miRNAs (97%), only miRs-409-5p and -572 were unpublished.…”

Section: Resultsmentioning

confidence: 99%

Dynamic Changes in the MicroRNA Expression Profile Reveal Multiple Regulatory Mechanisms in the Spinal Nerve Ligation Model of Neuropathic Pain

et al. 2011

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Neuropathic pain resulting from nerve lesions or dysfunction represents one of the most challenging neurological diseases to treat. A better understanding of the molecular mechanisms responsible for causing these maladaptive responses can help develop novel therapeutic strategies and biomarkers for neuropathic pain. We performed a miRNA expression profiling study of dorsal root ganglion (DRG) tissue from rats four weeks post spinal nerve ligation (SNL), a model of neuropathic pain. TaqMan low density arrays identified 63 miRNAs whose level of expression was significantly altered following SNL surgery. Of these, 59 were downregulated and the ipsilateral L4 DRG, not the injured L5 DRG, showed the most significant downregulation suggesting that miRNA changes in the uninjured afferents may underlie the development and maintenance of neuropathic pain. TargetScan was used to predict mRNA targets for these miRNAs and it was found that the transcripts with multiple predicted target sites belong to neurologically important pathways. By employing different bioinformatic approaches we identified neurite remodeling as a significantly regulated biological pathway, and some of these predictions were confirmed by siRNA knockdown for genes that regulate neurite growth in differentiated Neuro2A cells. In vitro validation for predicted target sites in the 3′-UTR of voltage-gated sodium channel Scn11a, alpha 2/delta1 subunit of voltage-dependent Ca-channel, and purinergic receptor P2rx ligand-gated ion channel 4 using luciferase reporter assays showed that identified miRNAs modulated gene expression significantly. Our results suggest the potential for miRNAs to play a direct role in neuropathic pain.

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“…Molecular network analysis enables us to characterize the most relevant pathways involved in the miRNA targets in silico (Murray et al, 2010). Human miRNA targets regulated by an individual miRNA generally constitutes function-associated molecules.…”

Section: Discussionmentioning

confidence: 99%

“…Human miRNA targets regulated by an individual miRNA generally constitutes function-associated molecules. It is therefore plausible that even a small change in the expression of a single miRNA could affect a wide range of signaling pathways and networks involved in diverse biological functions (Murray et al, 2010). Through the enrichment and function analysis using DAVID database, we propose that the target genes of the DE miRNA in the jaw tumor and non-survivors, may lead to the enhancement of many important biological processes, including positive regulation of cell proliferation (Figures S5, S6).…”

Section: Discussionmentioning

confidence: 99%

Human and Epstein-Barr Virus miRNA Profiling as Predictive Biomarkers for Endemic Burkitt Lymphoma

et al. 2017

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Endemic Burkitt lymphoma (eBL) is an aggressive B cell lymphoma and is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum malaria co-infections. Central to BL oncogenesis is the over-expression of the MYC proto-oncogene which is caused by a translocation of an Ig enhancer in approximation to the myc gene. While whole genome/transcriptome sequencing methods have been used to define driver mutations and transcriptional dysregulation, microRNA (miRNA) dysregulation and differential expression has yet to be fully characterized. We hypothesized that both human and EBV miRNAs contribute to eBL clinical presentation, disease progression, and poor outcomes. Using sensitive and precise deep sequencing, we identified miRNAs from 17 Kenyan eBL patient tumor samples and delineated the complement of both host and EBV miRNAs. One human miRNA, hsa-miR-10a-5p was found to be differentially expressed (DE), being down-regulated in jaw tumors relative to abdominal and in non-survivors compared to survivors. We also examined EBV miRNAs, which made up 2.7% of the miRNA composition in the eBL samples. However, we did not find any significant associations regarding initial patient outcome or anatomical presentation. Gene ontology analysis and pathway enrichment of previously validated targets of miR-10a-5p suggest that it can promote tumor cell survival as well as aid in evasion of apoptosis. To examine miR-10a-5p regulatory effect on gene expression in eBL, we performed a pairwise correlation coefficient analysis on the expression levels of all its validated targets. We found a significant enrichment of correlated target genes consistent with miR-10a-5p impacting expression. The functions of genes and their correlation fit with multiple target genes impacting tumor resilience. The observed downregulation of miR-10a and associated genes suggests a role for miRNA in eBL patient outcomes and has potential as a predictive biomarker that warrants further investigation.

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An in silico analysis of microRNAs: Mining the miRNAome

Cited by 39 publications

References 55 publications

PRMT5 is Required for Human Embryonic Stem Cell Proliferation But Not Pluripotency

PRMT5 is Required for Human Embryonic Stem Cell Proliferation But Not Pluripotency

Dynamic Changes in the MicroRNA Expression Profile Reveal Multiple Regulatory Mechanisms in the Spinal Nerve Ligation Model of Neuropathic Pain

Human and Epstein-Barr Virus miRNA Profiling as Predictive Biomarkers for Endemic Burkitt Lymphoma

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