Micro<scp>RNA</scp>‐20a‐5p contributes to hepatic glycogen synthesis through targeting p63 to regulate p53 and <scp>PTEN</scp> expression

Fang, Weiwei; Guo, Jun; Cao, Yuan; Wang, Shuyue; Pang, Cheng; Li, Meng; Dou, Lin; Man, Yong; Huang, Xiuqing; Shen, Tao; Li, Jian

doi:10.1111/jcmm.12835

Cited by 39 publications

(34 citation statements)

References 50 publications

(62 reference statements)

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“…Several targets have previously been reported and experimentally validated including CDKN1A, Smad4, p63, EGR2, E2F1, Rab27B, KIF26B and SDC2. 22,[26][27][28][29][30][31] However, none of these targets were found to be associated with the role of miR-20a-5p in the regulation of pulmonary surfactant metabolism in AT-II. Instead, we found that PTEN was a potential target of miR-20a in AT-II.…”

Section: Discussionmentioning

confidence: 98%

miR‐20a‐5p regulates pulmonary surfactant gene expression in alveolar type II cells

Gong

Chen

et al. 2019

J Cellular Molecular Medi

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MicroRNA (miRNA) critically controls gene expression in many biological processes, including lung growth and pulmonary surfactant biosynthesis. The present study was conducted to investigate whether miR‐20a‐5p had such regulatory functions on alveolar type II (AT‐II) cells. To accomplish this, miR‐20a‐5p–overexpressed and miR‐20a‐5p–inhibited adenoviral vectors were constructed and transfected into cultured AT‐II cells that were isolated from rat foetal lungs of 19 days' gestation. Transfection efficiency was confirmed by observing the fluorescence of green fluorescent protein (GFP) carried by the viral vector, whereas miR‐20a‐5p levels were verified by real‐time PCR. The CCK‐8 assay was used to compare the proliferation ability of AT‐II cells that had over‐ or underexpressed miR‐20a‐5p. The expression of surfactant‐associated proteins (SPs) and phosphatase and tensin homolog (PTEN) was measured by real‐time PCR and Western blotting. In AT‐II cells, transfection resulted in over‐ or under‐regulation of miR‐20a‐5p. While overexpression of miR‐20a‐5p promoted pulmonary surfactant gene expression, its underexpression inhibited it. Consistent with its role in negatively regulating the pulmonary surfactant gene, an opposite pattern was observed for miR‐20a‐5p regulation of PTEN. As a result, when miR‐20a‐5p was rendered overexpressed, PTEN was down‐regulated. By contrast, when miR‐20a‐5p was underexpressed, PTEN was up‐regulated. Neither overexpression nor underexpression of miR‐20a‐5p altered the cell proliferation. miR‐20a‐5p plays no role in proliferation of foetal AT‐II cells but is a critical regulator of surfactant gene expression. The latter appears to be achieved through a regulatory process that implicates expression of PTEN.

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Section: Discussionmentioning

confidence: 98%

miR‐20a‐5p regulates pulmonary surfactant gene expression in alveolar type II cells

Gong

Chen

et al. 2019

J Cellular Molecular Medi

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“…MiR-291b-3p levels were reversely transcribed using Taq-Man MicroRNA Reverse Transcription Kit (Applied Biosystems, Foster City, California, USA). The expression of miR-291b-3p was normalized to that of the U6 snRNA as previously described38. For gene expression analysis, real-time PCR was performed using a BioRad IQ5 instrument and SYBR mix (TransGen Biotech, Beijing, China).…”

Section: Methodsmentioning

confidence: 99%

Hepatic MiR-291b-3p Mediated Glucose Metabolism by Directly Targeting p65 to Upregulate PTEN Expression

Guo

Dou

Meng

et al. 2017

Sci Rep

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Several studies have suggested an important role of miR-291b-3p in the development of embryonic stem cells. In previous study, we found that the expression of miR-291b-3p was significantly upregulated in the liver of db/db mice. However, the role of miR-291b-3p in glucose metabolism and its underlying mechanisms remain unknown. In the present study, we demonstrated that miR-291b-3p was abundantly expressed in the liver. Of note, hepatic miR-291b-3p expression was upregulated in HFD-fed mice and induced by fasting in C57BL/6 J normal mice. Importantly, hepatic inhibition miR-291b-3p expression ameliorated hyperglycemia and insulin resistance in HFD-fed mice, whereas hepatic overexpression of miR-291b-3p led to hyperglycemia and insulin resistance in C57BL/6 J normal mice. Further study revealed that miR-291b-3p suppressed insulin-stimulated AKT/GSK signaling and increased the expression of gluconeogenic genes in hepatocytes. Moreover, we identified that p65, a subunit of nuclear factor-κB (NF-κB), is a target of miR-291b-3p by bioinformatics analysis and luciferase reporter assay. Silencing of p65 significantly augmented the expression of PTEN and impaired AKT activation. In conclusion, we found novel evidence suggesting that hepatic miR-291b-3p mediated glycogen synthesis and gluconeogenesis through targeting p65 to regulate PTEN expression. Our findings indicate the therapeutic potential of miR-291b-3p inhibitor in hyperglycemia and insulin resistance.

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“…Further analysis of the RNA-seq and miRNA-seq data validated that several tumor-related genes, including TP63 (target of miR-20a and let-7i), BCL2 (target of miR-195 and miR-34), and PDGFRb (target of miR-195), were transcriptional targets of p53 and that these miRNAs were also directly regulated by p53 (3,4,(24)(25)(26). These results revealed a global mechanism that increased understanding of the influences of the NOP14/mutp53 regulatory axis on its downstream molecules, that is, the expression of the p53 transcriptional effectors was also found to be regulated by p53-induced miRNAs at the posttranscriptional level (Fig.…”

Section: Discussionmentioning

confidence: 89%

Pancreatic Cancer Progression Relies upon Mutant p53-Induced Oncogenic Signaling Mediated by NOP14

Liu

You

et al. 2017

Cancer Research

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Mutant p53 (mutp53) proteins promote tumor invasion and metastasis in pancreatic ductal adenocarcinoma (PDAC). However, the mechanism underlying sustained activation of mutp53 oncogenic signaling is currently unclear. In this study, we report that NOP14 nucleolar protein (NOP14) expression is upregulated in PDAC tumors and metastatic tissue specimens. NOP14 overexpression promoted cell motility, whereas NOP14 inhibition decreased invasive capacity of PDAC cells. In vivo invasion assays conducted on established subcutaneously, orthotopically, and intravenously injected tumor mouse models also indicated NOP14 as a promoter of PDAC metastasis. Mechanistically, mutp53 was validated as a functional target of NOP14; NOP14 primed tumor invasion and metastasis by increasing the stability of mutp53 mRNA. The NOP14/mutp53 axis suppressed p21 expression at both the transcriptional and posttranscriptional levels via induction of miR-17-5p in PDAC cells. In vivo, high NOP14 expression in PDAC patient tumors correlated with local metastasis and lymph invasion. Overall, our findings define a novel mechanism for understanding the function of NOP14 in the metastatic cascade of PDAC. Targeting NOP14 allows for effective suppression of tumor invasion in a mutp53-dependent manner, implicating NOP14 inhibition as a potential approach for attenuating metastasis in p53-mutant tumors.

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MicroRNA‐20a‐5p contributes to hepatic glycogen synthesis through targeting p63 to regulate p53 and PTEN expression

Cited by 39 publications

References 50 publications

miR‐20a‐5p regulates pulmonary surfactant gene expression in alveolar type II cells

miR‐20a‐5p regulates pulmonary surfactant gene expression in alveolar type II cells

Hepatic MiR-291b-3p Mediated Glucose Metabolism by Directly Targeting p65 to Upregulate PTEN Expression

Pancreatic Cancer Progression Relies upon Mutant p53-Induced Oncogenic Signaling Mediated by NOP14

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