miR-107 orchestrates ER stress induction and lipid accumulation by post-transcriptional regulation of fatty acid synthase in hepatocytes

Bhatia, Himanshi; Verma, Gaurav; Datta, Malabika

doi:10.1016/j.bbagrm.2014.02.009

Cited by 51 publications

(30 citation statements)

References 48 publications

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“…Bhatia et al [30] transfected HepG2 hepatocytes with miRNA-107 at various doses and they observed that, using the most common dose in transfection studies (25 nM), no changes in FAS protein expression were observed. When we measured FAS protein expression, we found no change in resveratrol-treated rats.…”

Section: Discussionmentioning

confidence: 99%

Are miRNA-103, miRNA-107 and miRNA-122 Involved in the Prevention of Liver Steatosis Induced by Resveratrol?

et al. 2017

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The aim of the present study was to determine whether the reduction in liver fat previously observed in our laboratory in a cohort of rats which had been fed an obesogenic diet was mediated by changes in the expression of microRNA (miRNA)-103-3p, miRNA-107-3p and miRNA-122-5p, which represent 70% of total miRNAs in the liver, as well as in their target genes. The expression of the three analysed miRNAs was reduced in rats treated with resveratrol. A reduction in sterol-regulatory element binding protein 1 (SREBP1) and an increase in carnitine palmitoyltransferase 1a (CPT1a) were observed in resveratrol-treated rats. No changes were found in fatty acid synthase (FAS). In cultured hepatocytes, SREBP1 protein was increased after the transfection of each miRNA. FAS protein expression was decreased after the transfection of miRNA-122-5p, and CPT1a protein was down-regulated by the over-expression of miRNA-107-3p. This study provides new evidences which show that srebf1 is a target gene for miRNA-103-3p and miRNA-107-3p, fasn a target gene for miRNA-122-5p and cpt1a a target gene for miRNA-107-3p. Moreover, the reduction in liver steatosis induced by resveratrol in rats fed an obesegenic diet is mediated, at least in part, by the increase in CPT1a protein expression and activity, via a decrease in miRNA-107-3p expression.

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Section: Discussionmentioning

confidence: 99%

Are miRNA-103, miRNA-107 and miRNA-122 Involved in the Prevention of Liver Steatosis Induced by Resveratrol?

et al. 2017

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“…Concerning the molecular functions of miR-107, various biological functions in human physiological systems, such as the central nervous system [60][61][62] , the circadian system 63 , angiogenesis 64 , lipid metabolism 65,66 , glycometabolism 67 and inflammation 68 , have been reported. Regarding the function of miR-107 in cancer, reduced miR-107 expression has been reported in various types of cancer [69][70][71][72][73][74][75][76][77][78] , and several recent studies have identified the tumor suppressor functions of miR-107.…”

Section: Discussionmentioning

confidence: 99%

Depleted Tumor Suppressor miR-107 in Plasma Relates to Tumor Progression and Is a Novel Therapeutic Target in Pancreatic Cancer

Imamura

Komatsu

Ichikawa

et al. 2017

Journal of the American College of Surgeons

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This study explored decreased tumor suppressor microRNA (miRNA) plasma levels in pancreatic cancer (PCa) patients to clarify their potential as novel biomarkers and therapeutic targets. We used the microRNA array-based approach to select candidates by comparing plasma levels between PCa patients and healthy volunteers. Six down-regulated miRNAs (miR-107, miR-126, miR-451, miR-145, miR-491-5p, and miR-146b-5p) were selected. Small-and large-scale analyses using samples from 100 PCa patients and 80 healthy volunteers revealed that miR-107 was the most down-regulated miRNA in PCa patients compared with healthy volunteers (P < 0.0001; area under the receiver-operating characteristic curve, 0.851). A low miR-107 plasma level was significantly associated with advanced T stage, N stage, and liver metastasis and was an independent factor predicting poor prognosis in PCa patients (P = 0.0424; hazard ratio, 2.95). miR-107 overexpression in PCa cells induced G1/S arrest with the production of p21 and inhibited cell proliferation through the transcriptional regulation of Notch2. In vivo, the restoration and maintenance of the miR-107 plasma level significantly inhibited tumor progression in mice. Depletion of the tumor suppressor miR-107 in plasma relates to tumor progression and poor outcomes. The restoration of the plasma miR-107 level might be a novel anticancer treatment strategy for PCa.Pancreatic cancer (PCa) is the fourth leading cause of cancer-related death in Japan and the United States 1 and the seventh worldwide 2 . PCa is one of the most aggressive cancer types and constitutes a global health problem, with more than 330,000 cancer-related deaths annually 2 . Although perioperative chemo-and/or radiotherapy regimens, surgical techniques and perioperative management have greatly progressed, PCa continues to present an extremely poor prognosis. Even now, the median survival time of PCa patients is 5 to 8 months, and their 5-year survival rate is less than 10%. This is because PCa develops with no symptoms, local invasiveness, or metastases to distant organs in the early stage of its clinical course [3][4][5] . Therefore, novel early diagnostic tools and effective treatment strategies are urgently needed to improve the survival rate of PCa patients.Because understanding the molecular mechanisms of tumorigenesis and identifying clinical biomarkers and molecular targets for PCa contribute to improving the management of this lethal disease, several studies have attempted to detect the biological factors involved in the malignant potential of PCa 6, 7 . Nevertheless, in clinical settings, no molecule has been used as an early diagnostic biomarker, and only a few molecules have been

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“…miRNAs play extremely important roles in regulating gene expression and have been reported to be instrumental in mediating liver biology and disease in mammals (Bandiera et al, 2015; Bhatia et al, 2014). The miR-29 family is one of the best-known miRNA families, which has been associated with intermediate lipid metabolites such as ceramide and diacylglycerol (Yang et al, 2014b; Mattis et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

miR-29a modulates SCD expression and is regulated in response to a saturated fatty acids diet in juvenile GIFT (Oreochromis niloticus)

Qiang

Sun

et al. 2017

Journal of Experimental Biology

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MicroRNAs (miRNAs) are small non-coding RNAs that regulate target gene expression by binding to the 3′ untranslated region (3′ UTR) of the target mRNA. MiRNAs regulate a large variety of genes, including those involved in liver biology and disease. Here, we report for the first time that miR-29a post-transcriptionally regulates stearoyl-CoA desaturase (SCD) by binding to its 3′ UTR in genetically improved farmed tilapia (GIFT), Oreochromis niloticus, as shown by a 3′ UTR luciferase reporter assay. miR-29a antagomir treatment in vivo resulted in significant upregulation of SCD expression. We found that miR-29a expression was negatively correlated with SCD expression in GIFT liver. Inhibition of miR-29a led to a significant increase in SCD expression on day 60 induced by a saturated fatty acid diet, thereby increasing conversion of 16:0 and 18:0 to 16:1 and 18:1, respectively, and activating serum insulin, which would favor glucose and lipid uptake by the liver. These results indicate that miR-29a regulates SCD levels by binding to its 3′ UTR, and this interaction affects saturated fatty acid stress induction and insulin and lipid accumulation in serum. Our results suggest that miR-29a is critical in regulating lipid metabolism homeostasis in GIFT liver, and this might provide a basis for understanding the biological processes and therapeutic intervention encountered in fatty liver.

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miR-107 orchestrates ER stress induction and lipid accumulation by post-transcriptional regulation of fatty acid synthase in hepatocytes

Cited by 51 publications

References 48 publications

Are miRNA-103, miRNA-107 and miRNA-122 Involved in the Prevention of Liver Steatosis Induced by Resveratrol?

Are miRNA-103, miRNA-107 and miRNA-122 Involved in the Prevention of Liver Steatosis Induced by Resveratrol?

Depleted Tumor Suppressor miR-107 in Plasma Relates to Tumor Progression and Is a Novel Therapeutic Target in Pancreatic Cancer

miR-29a modulates SCD expression and is regulated in response to a saturated fatty acids diet in juvenile GIFT (Oreochromis niloticus)

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