MiRNA–miRNA synergistic network: construction via co-regulating functional modules and disease miRNA topological features

Xu, Juan; Li, Chuan Xing; Li, Yong Sheng; Lv, Jun; Ma, Ye; Shao, Ting; Xu, Liang; Wang, Xiaocong; Du, Lei; Zhang, Yun Peng; Jiang, Wei; Li, Chun Quan; Xiao, Yun; Li, Xia

doi:10.1093/nar/gkq832

Cited by 250 publications

(193 citation statements)

References 55 publications

(68 reference statements)

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“…Complex diseases are affected by several miRNAs rather than a single miRNA. So, it is to be of great significance to identify miRNA synergism and thereby further determine miRNA functions at a system-wide level and investigate disease miRNA features in the miRNA-miRNA synergistic network from a new view [84]. Here, we suggested that these miRNAs share some target genes, although limitations exist in the current data, the results uncovered here are important for understanding the key roles of miRNAs in diseases, the results present here provide a new insight into the global topological properties of disease miRNAs in the comprehensive miRNA synergistic network.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive identification and profiling of Nile tilapia (Oreochromis niloticus) microRNAs response to Streptococcus agalactiae infection through high-throughput sequencing

Wang

Gan

Cai

et al. 2016

Fish & Shellfish Immunology

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Section: Discussionmentioning

confidence: 99%

Comprehensive identification and profiling of Nile tilapia (Oreochromis niloticus) microRNAs response to Streptococcus agalactiae infection through high-throughput sequencing

Wang

Gan

Cai

et al. 2016

Fish & Shellfish Immunology

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“…Furthermore, the putative seed sequences for miRNAs in the 3′ UTRs of mRNAs are often clustered (39). Each of the Runx2-targeting miRNAs is predicted to have hundreds of other targets.…”

Section: Discussionmentioning

confidence: 99%

A program of microRNAs controls osteogenic lineage progression by targeting transcription factor Runx2

Zhang

Xie

Stein

et al. 2011

Bone

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Lineage progression in osteoblasts and chondrocytes is stringently controlled by the cell-fate-determining transcription factor Runx2. In this study, we directly addressed whether microRNAs (miRNAs) can control the osteogenic activity of Runx2 and affect osteoblast maturation. A panel of 11 Runx2-targeting miRNAs (miR-23a, miR-30c, miR-34c, miR-133a, miR-135a, miR-137, miR-204, miR-205, miR-217, miR-218, and miR-338) is expressed in a lineage-related pattern in mesenchymal cell types. During both osteogenic and chondrogenic differentiation, these miRNAs, in general, are inversely expressed relative to Runx2. Based on 3′UTR luciferase reporter, immunoblot, and mRNA stability assays, each miRNA directly attenuates Runx2 protein accumulation. Runx2-targeting miRNAs differentially inhibit Runx2 protein expression in osteoblasts and chondrocytes and display different efficacies. Thus, cellular context contributes to miRNA-mediated regulation of Runx2. All Runx2-targeting miRNAs (except miR-218) significantly impede osteoblast differentiation, and their effects can be reversed by the corresponding anti-miRNAs. These findings demonstrate that osteoblastogenesis is limited by an elaborate network of functionally tested miRNAs that directly target the osteogenic master regulator Runx2.osteogenesis | chondrogenesis | post-transcriptional regulation C ell-fate determination and subsequent lineage progression of phenotype-committed cells are mediated by master regulatory transcription factors that integrate multiple cell-signaling inputs and generate epigenetic changes in chromatin to modulate gene expression. Transcription factors are components of positive and negative feedback loops that initiate or maintain the acquisition of distinct biological states. Epigenomic mechanisms, including attenuation of mRNA and protein expression by small noncoding microRNAs (miRNAs) (1), permit effective control of gene expression beyond genomic interactions between transcription factors and their cognate elements in gene promoters. The biological potency of miRNAs, which are generated by the RNA processing enzyme Dicer, is based on their ability to control mRNA accumulation and/or protein synthesis through specific interactions with the 3′UTRs of target genes (1). Gene regulatory networks involving transcription factors and miRNAs may mutually reinforce cell fates and support phenotypic maturation of lineage-committed cells.Osteogenic differentiation provides an effective cell model in which to define both epigenetic and epigenomic mechanisms required for cell-fate determination and phenotypic differentiation. Differentiation of multipotent mesenchymal stem cells into the osteoblast lineage and maturation of osteoprogenitors are controlled by multiple extracellular ligands [e.g., BMPs, WNTs, and FGFs] (2-4) that direct the activities of key transcription factors, including Runx2, Osterix, and different classes of homeodomain proteins (5-8). Runx2 is a critical regulator of the osteogenic lineage, and its epigenetic functions modulate ...

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“…Furthermore, synergistic regulations among multiple miRNAs are important to understand the mechanisms of complex post-transcriptional regulations in humans. [26][27] Complex diseases are affected by several miRNAs rather than a single miRNA. Azra Krek et al have shown that MIR375, MIR124, and MIR-LET7B jointly regulate MTPN (myotrophin), a 12-kDa soluble protein that can initiate cardiac hypertrophy, providing evidence for coordinate miRNA control in mammals.…”

Section: Discussionmentioning

confidence: 99%

Burkholderia pseudomallei survival in lung epithelial cells benefits from miRNA-mediated suppression of ATG10

Yao

Zhu

et al. 2015

Autophagy

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(2015) Burkholderiapseudomallei survival in lung epithelial cells benefits from miRNA-mediated suppression of ATG10, Autophagy, 11:8, 1293-1307, DOI: 10.1080/15548627.2015 Keywords: ATG10, autophagy, Burkholderia pseudomallei, DNA methylation, MIR4458, MIR4667-5p, MIR4668-5pAbbreviations: 3-MA, 3-methyladenine; 3 0 UTR, 3 0 -untranslated region; 5-Aza-CdR, 5-aza-2 0 -deoxycytidine; ACTB, actin, b; ATG4C, autophagy-related 4C, cysteine peptidase; ATG5, autophagy-related 5; ATG10, autophagy-related 10; ATG12, autophagyrelated 12; B. pseudomallei, Burkholderia pseudomallei; CFU, colony forming unit; CQ, chloroquine; DNMT1, DNA (cytosine-5-)-methyltransferase 1; DRAM2, DNA-damage regulated autophagy modulator 2; MAP1LC3B, microtubule-associated protein 1 light chain 3 b; miRNAs, microRNAs; MOI, multiplicity of infection; MSP, methylation-specific PCR; PBS, phosphate-buffered saline; p.i., postinfection; Rapa, rapamycin; siRNA, small interfering RNA; SQSTM1, sequestosome 1; TEM, transmission electron microscopy.Burkholderia pseudomallei is the causative agent of melioidosis, a disease with high mortality, which is prevalent in tropical regions of the world. A recent study shows that B. pseudomallei can survive inside mammalian cells because of its ability to actively evade cell autophagy. However, the underlying mechanisms remain unclear. In the present study, based on microarray screening, we found that ATG10 was downregulated following B. pseudomallei infection in A549 human lung epithelial cells. Forced expression of ATG10 accelerated the elimination of intracellular B. pseudomallei by enhancing the process of autophagy. Moreover, MIR4458, MIR4667-5p, and MIR4668-5p were found, by microarray screening, to be upregulated in response to B. pseudomallei infection. These 3 novel miRNAs, MIR4458, MIR4667-5p, and MIR4668-5p, targeted to the 3 0 -untranslated region of ATG10 in different time-course and spatial manners. Upregulation of these miRNAs reduced the level of ATG10 and inhibited autophagy, leading to increasing survival rate of intracellular B. pseudomallei. Furthermore, the increase of these miRNAs was correlated with the reduced promoter methylation status in A549 cells in response to B. pseudomallei infection. Our results reveal that 3 novel miRNAs regulate autophagymediated elimination of B. pseudomallei by targeting ATG10, and provide potential targets for clinical treatment.

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MiRNA–miRNA synergistic network: construction via co-regulating functional modules and disease miRNA topological features

Cited by 250 publications

References 55 publications

Comprehensive identification and profiling of Nile tilapia (Oreochromis niloticus) microRNAs response to Streptococcus agalactiae infection through high-throughput sequencing

Comprehensive identification and profiling of Nile tilapia (Oreochromis niloticus) microRNAs response to Streptococcus agalactiae infection through high-throughput sequencing

A program of microRNAs controls osteogenic lineage progression by targeting transcription factor Runx2

Burkholderia pseudomallei survival in lung epithelial cells benefits from miRNA-mediated suppression of ATG10

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