Unsaturated fatty acids inhibit the expression of tumor suppressor phosphatase and tensin homolog (PTEN) via microRNA-21 up-regulation in hepatocytes

Vinciguerra, Manlio; Sgroi, Antonino; Veyrat-Durebex, Christelle; Rubbia‐Brandt, Laura; Bühler, Léo H.; Foti, Michelangelo

doi:10.1002/hep.22737

Cited by 184 publications

(149 citation statements)

References 40 publications

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“…40 The increased expression of levels of miR-200a, miR-200b, miR-429, belonging to the same genomic cluster, were found in our model of NAFLD, and it is in agreement with other studies. 26,27 Contrarily from that observed by Vinciguerra et al, 41 but equally to Li et al, 26 we observed a significant downregulation of miR-21 that seems to be unrelated to PTEN expression, but to other potential targets such as LITAF. Recently, an interesting role in liver fibrogenesis was attributed to the upregulation of miR-27a and miR-27b 42 ; in our model, the downregulation of miR-27a appears mainly associated to the inflammatory molecules and fatty acid metabolism.…”

Section: Discussionsupporting

confidence: 82%

Mirnome analysis reveals novel molecular determinants in the pathogenesis of diet-induced nonalcoholic fatty liver disease

Alisi

Sacco

Bruscalupi

et al. 2011

Laboratory Investigation

178

116

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Nonalcoholic fatty liver disease (NAFLD) is an emerging disease with a broad spectrum of liver conditions. The complex molecular pathogenesis of NAFLD is still unclear. In this study, we conducted an analysis of microRNA (miRNA) expression profiles in liver of rats made NAFLD by different diets. To this aim, Sprague-Dawley rats were fed ad libitum for 3 months with different diets: standard diet (SD), diet enriched in fats and low in carbohydrates (HFD), SD with high fructose (SD-HF) and diet with high levels of fats and fructose (HFD-HF). Our results demonstrated that the treatment with different dietetic regimens caused a significant increase of the body weight and the alteration of some metabolic parameters compared with control animals, as well as various liver injuries. The miRNAs analysis showed the significant downregulation of three miRNAs (miR-122, miR-451 and miR-27) and the upregulation of miR-200a, miR-200b and miR-429 in HFD, SD-HF and HFD-HF rats. Besides, miR-21 expression was significantly decreased only in fructose-enriched diets. These miRNAs target molecules involved in the control of lipid and carbohydrate metabolism, signal transduction, cytokine and chemokine-mediated signaling pathway and apoptosis. Western blot analysis of PKCd, LITAF, ALDOLASE-A, p38MAPK, PTEN, LIPIN1, EPHRIN-A1, EPHA2 and FLT1 showed a diet-induced deregulation of all these proteins. Interestingly, the expression pattern of LITAF, PTEN, LIPIN1, EPHRIN-A1, EPHA2 and FLT1 might be well explained by the trend of their specific mRNAs, by potentially regulatory miRNAs, or both. In conclusion, we highlight for the first time the potential involvement of novel determinants (miRNAs and proteins) in the molecular pathogenesis of diet-induced NAFLD.

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Section: Discussionsupporting

confidence: 82%

Mirnome analysis reveals novel molecular determinants in the pathogenesis of diet-induced nonalcoholic fatty liver disease

Alisi

Sacco

Bruscalupi

et al. 2011

Laboratory Investigation

178

116

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“…Some studies have also shown that macrophages actively intake exosomes containing miR molecules, which could be another way of delivering the regulatory message of the miRs from one cell to another (Lasser, et al 2011). According to Vinciguerra et al (2009) the up-regulation of miR-21…”

Section: Discussionmentioning

confidence: 99%

Circulating miR-21, miR-146a and Fas ligand respond to postmenopausal estrogen-based hormone replacement therapy – A study with monozygotic twin pairs

Kangas

Pöllänen

Rippo

et al. 2014

Mechanisms of Ageing and Development

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“…However, the molecular mechanisms underlying the NF-κB effect are not clear. PDCD4 is negatively regulated by miR-21 (23), and at least in myeloma cells, miR-21 expression is regulated by NF-κB (36,37). We therefore hypothesized that NF-κB might regulate β cell death through miR-21 and PDCD4.…”

Section: Pdcd4 Deficiency Prevents Islet β Cell Death Whereas Pdcd4mentioning

confidence: 99%

The microRNA-21−PDCD4 axis prevents type 1 diabetes by blocking pancreatic β cell death

Ruan

Wang

Kameswaran

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

187

148

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Death of pancreatic β cells is a pathological hallmark of type 1 diabetes (T1D). However, the molecular mechanisms of β cell death and its regulation are poorly understood. Here we describe a unique regulatory pathway of β cell death that comprises microRNA-21, its target tumor suppressor PDCD4, and its upstream transcriptional activator nuclear factor-κB (NF-κB). In pancreatic β cells, c-Rel and p65 of the NF-κB family activated the mir21 gene promoter and increased miR-21 RNA levels; miR-21 in turn decreased the level of PDCD4, which is able to induce cell death through the Bax family of apoptotic proteins. Consequently, PDCD4 deficiency in pancreatic β cells renders them resistant to death, and PDCD4 deficiency in NOD or C57BL/6 mice conferred resistance to spontaneous diabetes and diabetes induced by autoimmune T cells or the β cell toxin streptozotocin (STZ). Thus, the NF-κB−microRNA-21−PDCD4 axis plays a crucial role in T1D and represents a unique therapeutic target for treating the disease.

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Unsaturated fatty acids inhibit the expression of tumor suppressor phosphatase and tensin homolog (PTEN) via microRNA-21 up-regulation in hepatocytes

Cited by 184 publications

References 40 publications

Mirnome analysis reveals novel molecular determinants in the pathogenesis of diet-induced nonalcoholic fatty liver disease

Mirnome analysis reveals novel molecular determinants in the pathogenesis of diet-induced nonalcoholic fatty liver disease

Circulating miR-21, miR-146a and Fas ligand respond to postmenopausal estrogen-based hormone replacement therapy – A study with monozygotic twin pairs

The microRNA-21−PDCD4 axis prevents type 1 diabetes by blocking pancreatic β cell death

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