miR-125b affects mitochondrial biogenesis and impairs brite adipocyte formation and function

Giroud, Maude; Pisani, Didier F.; Karbiener, Michael; Barquissau, Valentin; Ghandour, Rayane A.; Tews, Daniel; Fischer‐Posovszky, Pamela; Chambard, Jean-Claude; Knippschild, Uwe; Niemi, Tarja; Taittonen, Markku; Nuutila, Pirjo; Wabitsch, Martin; Herzig, Stephan; Virtanen, Kirsi A.; Langin, Dominique; Scheideler, Marcel; Amri, Ez-Zoubir

doi:10.1016/j.molmet.2016.06.005

Cited by 59 publications

(59 citation statements)

References 75 publications

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“…MicroRNA‐125b was targeted by Mcl‐1, Bcl‐w, and IL‐6R to promote cancer cell apoptosis . In addition, miR‐125b could modulate oxygen consumption and mitochondrial gene expression . Overexpression of miR‐125b enhanced the cytotoxicity of doxorubicin in doxorubicin‐resistant MCF‐7 cells.…”

Section: Introductionmentioning

confidence: 99%

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Long noncoding RNA LINC00152 promotes cell proliferation through competitively binding endogenous miR‐125b with MCL‐1 by regulating mitochondrial apoptosis pathways in ovarian cancer

et al. 2018

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Recently, an increasing number of studies have focused on the key function of long noncoding RNAs (lncRNAs) in biological activity. Abnormal lncRNA expression was found to relate to the development and pathogenesis of multiple cancers. LncRNA LINC00152 served as an oncogene in multiple cancers; however, its role in ovarian cancer remains unknown. In our research study, LINC00152 was upregulated in ovarian cancer tissues and cell lines. An increasing LINC00152 level was positively correlated with the histological grade, clinical stage, and poor prognosis of ovarian cancer patients. In addition, knockdown of LINC00152 reduced cell growth, induced cell apoptosis, and suppressed tumor growth. Moreover, we revealed that LINC00152 and Myeloid cell leukemia‐1 (MCL‐1) were targeted by miR‐125b and had the same miR‐125b combining site. The miR‐125b level was negatively correlated with the expression of LINC00152, while MCL‐1 was positively related to the LINC00152 level. MiR‐125b could affect LINC00152 levels as evaluated by qRT‐PCR. Finally, we affirmed that LINC00152 mediated cell proliferation by affecting MCL‐1 expression and MCL‐1‐mediated mitochondrial apoptosis pathways and by working as a competitive endogenous RNA (ceRNA) of miR‐125b. In summary, based on ceRNA theory, the combined research on miR‐125b and MCL‐1, and taking LINC00152 as a new study point, we provide new insight into the molecular mechanism of reversing cell proliferation in ovarian cancer.

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Section: Introductionmentioning

confidence: 99%

“…14 In addition, miR-125b could modulate oxygen consumption and mitochondrial gene expression. 15 Overexpression of miR-125b enhanced the cytotoxicity of doxorubicin in doxorubicin-resistant MCF-7 cells. This sensitization of miR-125b is caspase dependent and leads to a loss of mitochondrial membrane potential and mitochondrial outer membrane permeability.…”

mentioning

confidence: 99%

Long noncoding RNA LINC00152 promotes cell proliferation through competitively binding endogenous miR‐125b with MCL‐1 by regulating mitochondrial apoptosis pathways in ovarian cancer

et al. 2018

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“…Human multipotent adipose-derived stem cells characterization has been previously described [20,21]. Cells were grown and differentiated as previously described [36]. Stroma vascular fraction of mouse adipose depots from scWAT, gWAT and BAT was differentiated as previously described [37].…”

Section: Cell Culture and Stromal Vascular Fraction Preparationmentioning

confidence: 99%

“…ROI was defined by the surface of the well. RNA were extracted using TRIzol reagent as previously described [36]. All the experiments have been done at least 3 times.…”

Section: Gene Expression and Functional Analysis In Vitromentioning

confidence: 99%

HAND2 is a novel obesity-linked adipogenic transcription factor regulated by glucocorticoid signaling

Giroud

Tsokanos

Caratti

et al. 2020

Preprint

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Adipocytes are critical cornerstones of energy metabolism. While obesity-induced adipocyte dysfunction is associated with insulin resistance and systemic metabolic disturbances, adipogenesis, the formation of new adipocytes and healthy adipose tissue expansion are associated with metabolic benefits. Understanding the molecular mechanisms governing adipogenesis is of great clinical potential to efficiently restore metabolic health in obesity. Here we show that Heart-and neural crest derivatives-expressed protein 2 (HAND2) is an obesitylinked adipocyte transcription factor regulated by glucocorticoids and required for adipocyte differentiation in vitro. In a large cohort of humans with obesity, white adipose tissue (WAT)HAND2 expression was correlated to body-mass-index (BMI). The HAND2 gene was enriched in white adipocytes, induced early in differentiation and responded to dexamethasone, a typical glucocorticoid receptor (GR, encoded by NR3C1) agonist. Silencing of NR3C1 in human multipotent adipose-derived stem cells (hMADS) or deletion of GR in a transgenic conditional mouse model results in diminished HAND2 expression, establishing that adipocyte HAND2 is regulated by glucocorticoids via GR in vitro and in vivo. Using a combinatorial RNAseq approach we identified gene clusters regulated by the GR-HAND2 pathway. Interestingly, silencing of HAND2 impaired adipocyte differentiation in hMADS and primary mouse adipocytes. However, a conditional adipocyte Hand2 deletion mouse model using Cre under control of the Adipoq promoter did not mirror these effects on adipose tissue differentiation, indicating that Hand2 was required at stages prior to Adipoq expression. In summary, our study identifies HAND2 as a novel obesity-linked adipocyte transcription factor, highlighting new mechanisms of GR-dependent adipogenesis in human and mice.

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“…Transgenic overexpression of PRDM-16 in subcutaneous WAT protected mice from diet-induced obesity and insulin resistance [84]. In addition, injections of an miR-125b-5p inhibitor directly into WAT increased β3-adrenoceptor-mediated induction of UCP-1 and BAT browning [85]. …”

Section: Anti-obesity Strategies and Reduction Of Cardiovascular Riskmentioning

confidence: 99%

Regulation of visceral and epicardial adipose tissue for preventing cardiovascular injuries associated to obesity and diabetes

González

Moreno-Villegas

González-Bris

et al. 2017

Cardiovasc Diabetol

166

131

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Nowadays, obesity is seriously increasing in most of the populations all over the world, and is associated with the development and progression of high-mortality diseases such as type-2 diabetes mellitus (T2DM) and its subsequent cardiovascular pathologies. Recent data suggest that both body fat distribution and adipocyte phenotype, can be more determinant for fatal outcomes in obese patients than increased general adiposity. In particular, visceral adiposity is significantly linked to long term alterations on different cardiac structures, and in developed forms of myocardial diseases such as hypertensive and ischaemic heart diseases, and diabetic cardiomyopathy. Interestingly, this depot may be also related to epicardial fat accumulation through secretion of lipids, adipokines, and pro-inflammatory and oxidative factors from adipocytes. Thus, visceral adiposity and its white single-lipid-like adipocytes, are risk factors for different forms of heart disease and heart failure, mainly in higher degree obese subjects. However, under specific stimuli, some of these adipocytes can transdifferentiate to brown multi-mitochondrial-like adipocytes with anti-inflammatory and anti-apoptotic proprieties. Accordingly, in order to improve potential cardiovascular abnormalities in obese and T2DM patients, several therapeutic strategies have been addressed to modulate the visceral and epicardial fat volume and phenotypes. In addition to lifestyle modifications, specific genetic manipulations in adipose tissue and administration of PPARγ agonists or statins, have improved fat volume and phenotype, and cardiovascular failures. Furthermore, incretin stimulation reduced visceral and epicardial fat thickness whereas increased formation of brown adipocytes, alleviating insulin resistance and associated cardiovascular pathologies.

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miR-125b affects mitochondrial biogenesis and impairs brite adipocyte formation and function

Cited by 59 publications

References 75 publications

Long noncoding RNA LINC00152 promotes cell proliferation through competitively binding endogenous miR‐125b with MCL‐1 by regulating mitochondrial apoptosis pathways in ovarian cancer

Long noncoding RNA LINC00152 promotes cell proliferation through competitively binding endogenous miR‐125b with MCL‐1 by regulating mitochondrial apoptosis pathways in ovarian cancer

HAND2 is a novel obesity-linked adipogenic transcription factor regulated by glucocorticoid signaling

Regulation of visceral and epicardial adipose tissue for preventing cardiovascular injuries associated to obesity and diabetes

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