Circulating and visceral adipose miR-100 is down-regulated in patients with obesity and Type 2 diabetes

Pek, Sharon Li Ting; Sum, Chee Fang; Lin, Michelle Xueqin; Cheng, Anton; Wong, Michael; Lim, Su Chi; Tavintharan, Subramaniam

doi:10.1016/j.mce.2016.03.010

Cited by 48 publications

(36 citation statements)

References 45 publications

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“…The main characteristics extracted from various datasets are summarized in Table 1, which includes the number of patients investigated, the measurement platform, type of sample used and the identity of miRNAs in the study [23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81]. Comparing results from multiple tissues provides an overall view of the impact of miRNAs in T2DM pathology.…”

Section: Resultsmentioning

confidence: 99%

A Systematic Study of Dysregulated MicroRNA in Type 2 Diabetes Mellitus

Ding

Liang

et al. 2017

IJMS

108

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MicroRNAs (miRNAs) are small noncoding RNAs that modulate the cellular transcriptome at the post-transcriptional level. miRNA plays important roles in different disease manifestation, including type 2 diabetes mellitus (T2DM). Many studies have characterized the changes of miRNAs in T2DM, a complex systematic disease; however, few studies have integrated these findings and explored the functional effects of the dysregulated miRNAs identified. To investigate the involvement of miRNAs in T2DM, we obtained and analyzed all relevant studies published prior to 18 October 2016 from various literature databases. From 59 independent studies that met the inclusion criteria, we identified 158 dysregulated miRNAs in seven different major sample types. To understand the functional impact of these deregulated miRNAs, we performed targets prediction and pathway enrichment analysis. Results from our analysis suggested that the altered miRNAs are involved in the core processes associated with T2DM, such as carbohydrate and lipid metabolisms, insulin signaling pathway and the adipocytokine signaling pathway. This systematic survey of dysregulated miRNAs provides molecular insights on the effect of deregulated miRNAs in different tissues during the development of diabetes. Some of these miRNAs and their mRNA targets may have diagnostic and/or therapeutic utilities in T2DM.

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Section: Resultsmentioning

confidence: 99%

A Systematic Study of Dysregulated MicroRNA in Type 2 Diabetes Mellitus

Ding

Liang

et al. 2017

IJMS

108

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“…Expression of circulating miR-100-5p was significantly decreased in obese normoglycemic subjects and subjects with type 2 diabetes mellitus (T2DM) compared to healthy, lean individuals. Moreover, in visceral adipose tissue, expression of miR-100 was lower in obese subjects with T2DM compared to obese subjects without T2DM ( 112 ).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA expression profiles and type 1 diabetes mellitus: systematic review and bioinformatic analysis

Assmann

Recamonde‐Mendoza

Souza

et al. 2017

Endocrine Connections

126

107

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Growing evidence indicates that microRNAs (miRNAs) have a key role in processes involved in type 1 diabetes mellitus (T1DM) pathogenesis, including immune system functions and beta-cell metabolism and death. Although dysregulated miRNA profiles have been identified in T1DM patients, results are inconclusive; with only few miRNAs being consistently dysregulated among studies. Thus, we performed a systematic review of the literature on the subject, followed by bioinformatic analysis, to point out which miRNAs are dysregulated in T1DM-related tissues and in which pathways they act. PubMed and EMBASE were searched to identify all studies that compared miRNA expressions between T1DM patients and non-diabetic controls. Search was completed in August, 2017. Those miRNAs consistently dysregulated in T1DM-related tissues were submitted to bioinformatic analysis, using six databases of miRNA–target gene interactions to retrieve their putative targets and identify potentially affected pathways under their regulation. Thirty-three studies were included in the systematic review: 19 of them reported miRNA expressions in human samples, 13 in murine models and one in both human and murine samples. Among 278 dysregulated miRNAs reported in these studies, 25.9% were reported in at least 2 studies; however, only 48 of them were analyzed in tissues directly related to T1DM pathogenesis (serum/plasma, pancreas and peripheral blood mononuclear cells (PBMCs)). Regarding circulating miRNAs, 11 were consistently dysregulated in T1DM patients compared to controls: miR-21-5p, miR-24-3p, miR-100-5p, miR-146a-5p, miR-148a-3p, miR-150-5p, miR-181a-5p, miR-210-5p, miR-342-3p, miR-375 and miR-1275. The bioinformatic analysis retrieved a total of 5867 validated and 2979 predicted miRNA–target interactions for human miRNAs. In functional enrichment analysis of miRNA target genes, 77 KEGG terms were enriched for more than one miRNA. These miRNAs are involved in pathways related to immune system function, cell survival, cell proliferation and insulin biosynthesis and secretion. In conclusion, eleven circulating miRNAs seem to be dysregulated in T1DM patients in different studies, being potential circulating biomarkers of this disease.

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“…Currently, it is also hypothesized that circulating miRNA expression profiles vary according to differences in BMI and T2DM, so that deregulation of miRNAs reflects adipose tissue expression [29]. In this respect, miR-100 has been associated with obesity and DM, as circulating and visceral adipose miR-100 was shown to be repressed in patients with obesity and T2DM [30]. Accordingly, miR-100 was suggested to modulate IGFR and mTOR and to mediate adipogenesis.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-496 and Mechanistic Target of Rapamycin Expression are Associated with Type 2 Diabetes Mellitus and Obesity in Elderly People

et al. 2019

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Background: Mechanistic target of rapamycin (mTOR) regulates lipid and glucose metabolism thus playing a key role in metabolic diseases like type 2 diabetes mellitus (T2DM). Recently, we demonstrated a functional interaction of microRNA-496 (miR-496) with mTOR and its impact on the regulation of human ageing. Objectives: As T2DM is most prevalent in older adults, we hypothesized that miR-496 may also have an impact on mTOR regulation in T2DM. Methods: Based on real-time PCR and enzyme-linked immunosorbent assay, mTOR gene and protein expression as well as miR-496 expression were monitored in peripheral blood mononuclear cells (PBMC) from T2DM patients (median age: 71) and healthy age- and BMI matched controls (median age: 69). Results: We demonstrated significant upregulation of phospho-mTOR and P70S6 Kinase (P70S6K) levels and significant downregulation of miR-496 in PBMC from elderly T2DM patients in comparison to a BMI and age-matched control cohort. Moreover, significant upregulation of phospho-mTOR protein and significant downregulation of miR-496 were observed in advanced stages of obesity. Conclusions: BMI-dependent upregulation of mTOR and the inverse expression profile of miR-496 observed in elderly T2DM patients suggest a correlation with T2DM. Hence, our results indicate a potential association of miR-496 with mTOR expression in elderly T2DM patients and obesity. Since phosphorylation of P70S6K was also elevated in T2DM patients, we conclude that mTOR signaling through TORC1 may be affected in the regulation of T2DM.

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Circulating and visceral adipose miR-100 is down-regulated in patients with obesity and Type 2 diabetes

Cited by 48 publications

References 45 publications

A Systematic Study of Dysregulated MicroRNA in Type 2 Diabetes Mellitus

A Systematic Study of Dysregulated MicroRNA in Type 2 Diabetes Mellitus

MicroRNA expression profiles and type 1 diabetes mellitus: systematic review and bioinformatic analysis

MicroRNA-496 and Mechanistic Target of Rapamycin Expression are Associated with Type 2 Diabetes Mellitus and Obesity in Elderly People

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