MicroRNA-30d Induces Insulin Transcription Factor MafA and Insulin Production by Targeting Mitogen-activated Protein 4 Kinase 4 (MAP4K4) in Pancreatic β-Cells

Zhao, Xiaomin; Mohan, Ramkumar; Özcan, Sabire; Tang, Xiaoqing

doi:10.1074/jbc.m112.362632

Cited by 120 publications

(101 citation statements)

References 39 publications

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“…miRNAs are small (approximately 22 nucleotides in length), noncoding singlestranded RNA molecules that can regulate numerous biological processes, including cellular differentiation (Nolte-'t Hoen et al, 2015), proliferation (Zhao et al, 2012), apoptosis (Yeh et al, 2012), angiogenesis (Caporali and Emanueli, 2011), the development of cancer , and the inhibition of tumor angiogenesis and growth (Luo et al, 2013;Tu et al, 2015). Endometriosis is a common, although mysterious and fascinating, gynecological condition with diverse clinical manifestations and high variability.…”

Section: Discussionmentioning

confidence: 99%

Microarray analysis of microRNA deregulation and angiogenesis-related proteins in endometriosis

Teng

et al. 2016

Genet. Mol. Res.

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ABSTRACT. We examined the aberrant microRNA (miRNA) expression profile responsible for the changes in angiogenesis observed in endometriotic lesions. This study revealed characteristic miRNA expression profiles associated with endometriosis in endometrial tissue and endometriotic lesions from the same patient, and their correlation with the most important angiogenic and fibrinolytic factors. miRNA expression was quantified using a microRNA array and reversetranscription microRNA polymerase chain reaction. Levels of vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor 2 (EGFR2), phosphatase and tensin homolog (PTEN), and C-X-C chemokine receptor type 4 (CXCR4) were quantified using enzyme-linked immunosorbent assay. The endometrial tissue showed significantly lower levels of miR-200b, miR-15a-5p, miR-19b-1-5p, miR-146a-5p, and miR-200c, and higher levels of miR-16-5p, miR106b-5p, and miR-145-5p. VEGFA was significantly upregulated, whereas EGFR2, PTEN, and CXCR4 were markedly downregulated, in the endometriotic tissues compared to that in the normal endometrial tissues. In conclusion, differences in the miRNA levels could modulate the expression of VEGFA, EGFR2, PTEN, and CXCR4, and may play an important role in the pathogenesis of endometriosis. The higher angiogenic and proteolytic activities observed in the eutopic endometrium might facilitate the implantation of endometrial cells at ectopic sites.

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Section: Discussionmentioning

confidence: 99%

Microarray analysis of microRNA deregulation and angiogenesis-related proteins in endometriosis

Teng

et al. 2016

Genet. Mol. Res.

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“…It has been reported that a class of endogenous, small non-coding miRNAs may act upon the mRNA of MAP4K4 and inhibit its translation (26). To further evaluate the regulating mechanisms of MAP4K4 in CRC, bioinformatics analysis was performed.…”

Section: Discussionmentioning

confidence: 99%

Role of microRNA-141 in colorectal cancer with lymph node metastasis

Chang

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The present study aimed to investigate the role of microRNA (miR)-141 in the pathogenesis of colorectal cancer (CRC). In total, 58 CRC patients were included in the present study. The mRNA and protein expression levels of mitogen-activated protein kinase 4 (MAP4K4) were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. The miRNA-141 expression was measured by RT-qPCR, while serum MAP4K4 content was detected by enzyme-linked immunosorbent assay. Natural killer (NK) cells and T cells in peripheral blood were detected by flow cytometry. The results indicated that the mRNA and protein expression levels of MAP4K4 were significantly elevated in the tumor tissues, lymph nodes (P<0.01) and serum (P<0.05) in CRC. Furthermore, the expression levels of MAP4K4 in CRC patients with lymph node metastasis were higher compared with those in patients without metastasis. Bioinformatics analysis revealed that MAP4K4 may be the target gene of miRNA-141. The expression levels of miRNA-141 in the tumor tissues, lymph nodes and serum were significantly decreased in CRC patients, with a more evident decline in cases with lymph node metastasis. In addition, the percentage of NK, CD3 + T and CD4 + T cells was significantly decreased, whilst the number of CD8 + T cells was significantly increased, in the peripheral blood in CRC. The present results showed that miRNA-141 was downregulated in CRC, which increased the expression levels of MAP4K4 and altered the anti-tumor response, further increasing the proliferation, invasion and metastasis of the tumors. These findings may contribute to improving the current understanding of the pathogenesis of CRC, and lead to the development of therapies involving miRNA-141.

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“…50 Additional clinical relevance is attributed to miR-30d as novel potential epigenetic drug for diabetes because it preserves mouse b-cells against TNFa-induced suppression of insulin expression and signaling. 51 Alternatively, the main target organs of insulin, namely liver, skeletal muscle, and adipose tissue might be also the targets of inflammatory pathways that could promote insulin resistance by means of epigenetic modifications (Fig. 1).…”

Section: B-cell Development and Functionmentioning

confidence: 99%

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

et al. 2017

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Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling b-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects. We discuss the effect of epigenetics on b-cell regeneration for cell replacement therapy, the emerging bioinformatics approaches for analyzing the epigenetic contribution to type 2 diabetes mellitus (T2DM), the epigenetic core of the transgenerational inheritance hypothesis in T2DM, and the epigenetic clinical trials on T2DM. Therefore, prevention or reversion of the epigenetic changes occurring during T2DM development may reduce the individual and societal burden of the disease.

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MicroRNA-30d Induces Insulin Transcription Factor MafA and Insulin Production by Targeting Mitogen-activated Protein 4 Kinase 4 (MAP4K4) in Pancreatic β-Cells

Cited by 120 publications

References 39 publications

Microarray analysis of microRNA deregulation and angiogenesis-related proteins in endometriosis

Microarray analysis of microRNA deregulation and angiogenesis-related proteins in endometriosis

Role of microRNA-141 in colorectal cancer with lymph node metastasis

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

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