Role of PTEN in TNFα induced insulin resistance

Bulger, David A; Conley, Jermaine; Conner, Spencer; Majumdar, Gipsy; Solomon, Solomon S.

doi:10.1016/j.bbrc.2015.04.063

Cited by 18 publications

(12 citation statements)

References 16 publications

(17 reference statements)

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“…In addition, overexpression of miR-106b-5p could abolish the pro-apoptotic effect of TNF-α as evidenced by DNA fragmentation assay and caspase-3 cleavage levels. In accordance with previous studies,[ 15 16 19 ] after TNF-α stimulation, apoptosis induction and caspase-3 activation were observed. Overexpression of miR-106b-5p partially reduced the pro-apoptotic effect of TNF-α in ECs.…”

Section: Discussionsupporting

confidence: 93%

MiR-106b-5p Inhibits Tumor Necrosis Factor-α-induced Apoptosis by Targeting Phosphatase and Tensin Homolog Deleted on Chromosome 10 in Vascular Endothelial Cells

Zhang

Chen

et al. 2016

Chinese Medical Journal

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Background:Apoptosis of endothelial cells (ECs) plays a key role in the development of atherosclerosis and there are also evidence indicated that phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a viable target in therapeutic approaches to prevent vascular ECs apoptosis. Aberrant miR-106b-5p expression has been reported in the plasma of patients with unstable atherosclerotic plaques. However, the role and underlying mechanism of miR-106-5p in the genesis of atherosclerosis have not been addressed. In this study, we explored the anti-apoptotic role of miR-106-5p by regulating PTEN expression in vascular ECs.Methods:Real-time reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the expression levels of miR-106b-5p in human atherosclerotic plaques and normal vascular tissues. Human umbilical vein endothelial cells (HUVEC) were transfected with miR-106b-5p mimic or negative control mimic, and apoptosis was induced by serum starvation and tumor necrosis factor-α (TNF-α) treat. Western blotting and real-time RT-PCR experiments were used to detect PTEN expression levels and TNF-α-induced apoptosis was evaluated by the activation of caspase-3 and cell DNA fragmentation levels in HUVEC.Results:The expression of miR-106b-5p was significantly downregulated in plaques than in normal vascular tissues. TNF-α significantly downregulated miR-106b-5p expression levels and upregulated activation of caspase-3 and cell DNA fragmentation levels in HUVEC. Overexpression of miR-106b-5p with miR-106b-5p mimic inhibited PTEN expression and TNF-α-induced apoptosis in HUVEC. Luciferase reporter assays confirmed that miR-106b-5p binds to PTEN mRNA 3’ untranslated region site.Conclusion:MiR-106b-5p could inhibit the expression of PTEN in vascular ECs, which could block TNF-α-induced activation of caspase-3, thus prevent ECs apoptosis in atherosclerosis diseases.

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Section: Discussionsupporting

confidence: 93%

MiR-106b-5p Inhibits Tumor Necrosis Factor-α-induced Apoptosis by Targeting Phosphatase and Tensin Homolog Deleted on Chromosome 10 in Vascular Endothelial Cells

Zhang

Chen

et al. 2016

Chinese Medical Journal

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“…Similarly, miR‐412 targets perilipin 2 ( PLIN2 ), which, when abrogated, protects against diet‐induced obesity, inflammation and hepatic steatosis , and has several predicted genes related to obesity, such as leptin receptor ( LEPR ) , interleukin 6 ( IL6 ) , Fas cell surface death receptor ( FAS ) and leptin ( LEP ). Finally, miR‐216A targets phosphatase and tensin homolog ( PTEN ) , a gene that has been implicated in type 2 diabetes and plays a central role in both insulin signalling/resistance and apoptosis . miR‐216A has several obesity‐related predicted genes, including CD44, LEPR, peroxisome proliferator‐activated receptor gamma ( PPARG ) , adiponectin receptor 1 ( ADIPOR1 ) , caveolin 1 ( CAV1 ) and caveolin 2 ( CAV2 ).…”

Section: Discussionmentioning

confidence: 99%

DNA methylation of miRNA coding sequences putatively associated with childhood obesity

et al. 2016

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“…PTEN-antisense treatment of C2C12 mouse myoblasts abolished TNFα-induced insulin resistance, which was associated with increased PTEN mRNA and protein levels [ 224 ]. Furthermore, PTEN increased expression in TNFα-treated H-411E rat liver cells was reverted by treatment with VO-OHpic [ 134 ]. Importantly, VO-OHpic treatment of mouse mesenteric arteries challenged with TNFα, or treatment of arteries from mice fed with high fat diet, prevented the induction of vascular insulin resistance [ 136 ].…”

Section: Pten Inhibition By Small Molecules In Human Disease Theramentioning

confidence: 99%

PTEN Inhibition in Human Disease Therapy

Pulido

2018

Molecules

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The tumor suppressor PTEN is a major homeostatic regulator, by virtue of its lipid phosphatase activity against phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3], which downregulates the PI3K/AKT/mTOR prosurvival signaling, as well as by its protein phosphatase activity towards specific protein targets. PTEN catalytic activity is crucial to control cell growth under physiologic and pathologic situations, and it impacts not only in preventing tumor cell survival and proliferation, but also in restraining several cellular regeneration processes, such as those associated with nerve injury recovery, cardiac ischemia, or wound healing. In these conditions, inhibition of PTEN catalysis is being explored as a potentially beneficial therapeutic intervention. Here, an overview of human diseases and conditions in which PTEN inhibition could be beneficial is presented, together with an update on the current status of specific small molecule inhibitors of PTEN enzymatic activity, their use in experimental models, and their limitations as research or therapeutic drugs.

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Role of PTEN in TNFα induced insulin resistance

Cited by 18 publications

References 16 publications

MiR-106b-5p Inhibits Tumor Necrosis Factor-α-induced Apoptosis by Targeting Phosphatase and Tensin Homolog Deleted on Chromosome 10 in Vascular Endothelial Cells

MiR-106b-5p Inhibits Tumor Necrosis Factor-α-induced Apoptosis by Targeting Phosphatase and Tensin Homolog Deleted on Chromosome 10 in Vascular Endothelial Cells

DNA methylation of miRNA coding sequences putatively associated with childhood obesity

PTEN Inhibition in Human Disease Therapy

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