MicroRNA-455-3p functions as a tumor suppressor by targeting eIF4E in prostate cancer

Zhao, Yongxiang; Yan, Min; Ye, Yun; Zhang, Jianguo; Zhang, Ruimin; Li, Yan; Wu, Xiangming; Liu, Qiang; Miao, Wei; Jiang, Huimin

doi:10.3892/or.2017.5502

Cited by 49 publications

(38 citation statements)

References 33 publications

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“…Thus, our results demonstrate that EPA increased thermogenic markers, in part via regulation of miR-455, a novel EPA target, upstream of PPAR-γ and PPAR-α , which inhibit Ncor to induce key thermogenic biomarkers. However, other studies have also reported potential roles of miR-455 in cancer, specifically as a tumor suppressor [61–63]. Taken together these studies suggest potential dual benefits for miR-455 in both cancer and energy balance.…”

Section: Discussionmentioning

confidence: 65%

Transcriptomic and microRNA analyses of gene networks regulated by eicosapentaenoic acid in brown adipose tissue of diet-induced obese mice

Pahlavani

Wijayatunga

Kalupahana

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Brown adipose tissue (BAT) dissipates chemical energy as heat via thermogenesis and protects against obesity by increasing energy expenditure. However, regulation of BAT by dietary factors remains largely unexplored at the mechanistic level. We investigated the effect of eicosapentaenoic acid (EPA) on BAT metabolism. Male C57BL/6J (B6) mice fed either a high-fat diet (HF, 45% kcal fat) or HF diet supplemented with EPA (HF-EPA, 6.75% kcal EPA) were used for 11 weeks. RNA sequencing (RNA-Seq) and microRNA (miRNA) profiling were performed on RNA from BAT using Illumina HiSeq and miSeq respectively. We conducted pathway analyses using ingenuity pathway analysis software (IPA®) and validated some genes and miRNAs using qPCR. We identified 479 genes that were differentially expressed (2-fold change, n=3, p ≤ 0.05) in BAT from HF compared to HF-EPA. Genes negatively correlated with thermogenesis such as hypoxia Inducible factor 1 alpha subunit inhibitor (Hif1αn), was downregulated by EPA. Pathways related to thermogenesis such as peroxisome proliferator-activated receptor (PPAR) were upregulated by EPA while pathways associated with obesity and inflammation such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were downregulated by EPA. MiRNA profiling identified nine and six miRNAs that were upregulated and downregulated by EPA, respectively (log2 fold change > 1.25, n=3, P ≤ 0.05). Key regulatory miRNAs were involved in thermogenesis, such as miR-455–3p and miR-129–5p were validated using qPCR. In conclusion, the depth of transcriptomic and miRNA profiling revealed novel mRNA-miRNA interaction networks in BAT which are involved in thermogenesis which regulated by EPA.

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Section: Discussionmentioning

confidence: 65%

Transcriptomic and microRNA analyses of gene networks regulated by eicosapentaenoic acid in brown adipose tissue of diet-induced obese mice

Pahlavani

Wijayatunga

Kalupahana

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…MiRNA-455 (miR-455) is recognized as a broadly conserved noncoding RNA that has been implicated in various cancers. The function of miR-455 has been confirmed in prostate cancer [51], gastric cancer [52], and oral squamous cancer cells [53]. However, the potential effect of miR-455-3p has rarely been explored in PDAC.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel genes associated with a poor prognosis in pancreatic ductal adenocarcinoma via a bioinformatics analysis

et al. 2019

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Pancreatic ductal adenocarcinoma (PDAC) is a class of the commonest malignant carcinomas. The present study aimed to elucidate the potential biomarker and prognostic targets in PDAC. The array data of GSE41368, GSE43795, GSE55643, and GSE41369 were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) and differentially expressed microRNAs (DEmiRNAs) in PDAC were obtained by using GEO2R, and overlapped DEGs were acquired with Venn Diagrams. Functional enrichment analysis of overlapped DEGs and DEmiRNAs was conducted with Metascape and FunRich, respectively. The protein–protein interaction (PPI) network of overlapped DEGs was constructed by STRING and visualized with Cytoscape. Overall survival (OS) of DEmiRNAs and hub genes were investigated by Kaplan–Meier (KM) plotter (KM plotter). Transcriptional data and correlation analyses among hub genes were verified through GEPIA and Human Protein Atlas (HPA). Additionally, miRNA targets were searched using miRTarBase, then miRNA–DEG regulatory network was visualized with Cytoscape. A total of 32 DEmiRNAs and 150 overlapped DEGs were identified, and Metascape showed that DEGs were significantly enriched in cellular chemical homeostasis and pathways in cancer, while DEmiRNAs were mainly enriched in signal transduction and Glypican pathway. Moreover, seven hub genes with a high degree, namely, V-myc avian myelocytomatosis viral oncogene homolog (MYC), solute carrier family 2 member 1 (SLC2A1), PKM, plasminogen activator, urokinase (PLAU), peroxisome proliferator activated receptor γ (PPARG), MET proto-oncogene, receptor tyrosine kinase (MET), and integrin subunit α 3 (ITGA3), were identified and found to be up-regulated between PDAC and normal tissues. miR-135b, miR-221, miR-21, miR-27a, miR-199b-5p, miR-143, miR-196a, miR-655, miR-455-3p, miR-744 and hub genes predicted poor OS of PDAC. An integrative bioinformatics analysis identified several hub genes that may serve as potential biomarkers or targets for early diagnosis and precision target treatment of PDAC.

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“…However, miR-455-3p is reportedly downregulated in prostate and colon cancer, and upregulation of miR-455-3p can inhibit the cancer proliferation [43, 44]. These studies imply that miR-455-3p can act as either an oncomiR or a tumor-suppressive miRNA depending on the tumor type.…”

Section: Discussionmentioning

confidence: 99%

Antagonizing miR-455-3p inhibits chemoresistance and aggressiveness in esophageal squamous cell carcinoma

Liu¹,

Zhu²,

Wu³

et al. 2017

Mol Cancer

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BackgroundThe plasticity of cancer stem cells (CSCs)/tumor-initiating cells (T-ICs) suggests that multiple CSC/T-IC subpopulations exist within a tumor and that multiple oncogenic pathways collaborate to maintain the CSC/T-IC state. Here, we aimed to identify potential therapeutic targets that concomitantly regulate multiple T-IC subpopulations and CSC/T-IC-associated pathways.MethodsA chemoresistant patient-derived xenograft (PDX) model of human esophageal squamous cell carcinoma (ESCC) was employed to identify microRNAs that contribute to ESCC aggressiveness. The oncogenic effects of microRNA-455-3p (miR-455-3p) on ESCC chemoresistance and tumorigenesis were examined by in vivo and in vitro chemoresistance, tumorsphere formation, side-population, and in vivo limiting dilution assays. The roles of miR-455-3p in activation of the Wnt/β-catenin and transforming growth factor-β (TGF-β)/Smad pathways were determined by luciferase and RNA immunoprecipitation assays.ResultsWe found that miR-455-3p played essential roles in ESCC chemoresistance and tumorigenesis. Treatment with a miR-455-3p antagomir dramatically chemosensitized ESCC cells and reduced the subpopulations of CD90+ and CD271+ T-ICs via deactivation of multiple stemness-associated pathways, including Wnt/β-catenin and TGF-β signaling. Importantly, miR-455-3p exhibited aberrant upregulation in various human cancer types, and was significantly associated with decreased overall survival of cancer patients.ConclusionsOur results demonstrate that miR-455-3p functions as an oncomiR in ESCC progression and may provide a potential therapeutic target to achieve better clinical outcomes in cancer patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0669-9) contains supplementary material, which is available to authorized users.

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MicroRNA-455-3p functions as a tumor suppressor by targeting eIF4E in prostate cancer

Cited by 49 publications

References 33 publications

Transcriptomic and microRNA analyses of gene networks regulated by eicosapentaenoic acid in brown adipose tissue of diet-induced obese mice

Transcriptomic and microRNA analyses of gene networks regulated by eicosapentaenoic acid in brown adipose tissue of diet-induced obese mice

Identification of novel genes associated with a poor prognosis in pancreatic ductal adenocarcinoma via a bioinformatics analysis

Antagonizing miR-455-3p inhibits chemoresistance and aggressiveness in esophageal squamous cell carcinoma

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