Circulating long noncoding RNA GAS5 levels are correlated to prevalence of type 2 diabetes mellitus

Miladinović, Branko; Patel, Achintya; Deland, Lauren A.; Mastorides, Stephen; Patel, Niketa A.

doi:10.1016/j.bbacli.2015.09.001

Cited by 145 publications

(133 citation statements)

References 30 publications

(36 reference statements)

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“…For example, DANCR, SNHG3 and SNHG1 are lncRNAs that promote tumour cell proliferation in liver cancer and imply poor prognoses [54-56]; moreover, these lncRNAs exhibited tendencies towards reduced expression in response to metformin treatment in our transcriptome profile. Another lncRNA, GAS5, is positively correlated with the incidence of type 2 diabetes [57], and its down-regulation by metformin might imply a potential improvement of the metabolic condition by metformin. However, the inhibition of this lncRNA has also been demonstrated to be involved in the progression of liver fibrosis and liver cancer [58, 59].…”

Section: Resultsmentioning

confidence: 99%

Metformin-Induced Changes of the Coding Transcriptome and Non-Coding RNAs in the Livers of Non-Alcoholic Fatty Liver Disease Mice

Guo

Zhou

Cheng

et al. 2018

Cell Physiol Biochem

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Background/Aims: Recent studies have suggested that changes in non-coding mRNA play a key role in the progression of non-alcoholic fatty liver disease (NAFLD). Metformin is now recommended and effective for the treatment of NAFLD. We hope the current analyses of the non-coding mRNA transcriptome will provide a better presentation of the potential roles of mRNAs and long non-coding RNAs (lncRNAs) that underlie NAFLD and metformin intervention. Methods: The present study mainly analysed changes in the coding transcriptome and non-coding RNAs after the application of a five-week metformin intervention. Liver samples from three groups of mice were harvested for transcriptome profiling, which covered mRNA, lncRNA, microRNA (miRNA) and circular RNA (circRNA), using a microarray technique. Results: A systematic alleviation of high-fat diet (HFD)-induced transcriptome alterations by metformin was observed. The metformin treatment largely reversed the correlations with diabetes-related pathways. Our analysis also suggested interaction networks between differentially expressed lncRNAs and known hepatic disease genes and interactions between circRNA and their disease-related miRNA partners. Eight HFD-responsive lncRNAs and three metformin-responsive lncRNAs were noted due to their widespread associations with disease genes. Moreover, seven miRNAs that interacted with multiple differentially expressed circRNAs were highlighted because they were likely to be associated with metabolic or liver diseases. Conclusions: The present study identified novel changes in the coding transcriptome and non-coding RNAs in the livers of NAFLD mice after metformin treatment that might shed light on the underlying mechanism by which metformin impedes the progression of NAFLD.

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Section: Resultsmentioning

confidence: 99%

Metformin-Induced Changes of the Coding Transcriptome and Non-Coding RNAs in the Livers of Non-Alcoholic Fatty Liver Disease Mice

Guo

Zhou

Cheng

et al. 2018

Cell Physiol Biochem

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“…GAS5 has been reported to be closely associated with various human diseases (8,28,30). GAS5 functions as a potential tumor suppressor and is downregulated in several types of cancer (28).…”

Section: Discussionmentioning

confidence: 99%

Association of long non‑coding RNA GAS5 and miR‑21 levels in CD4+ T cells with clinical features of systemic lupus erythematosus

et al. 2017

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Abstract. The present study aimed to assess the expression of growth arrest-specific 5 (GAS5) and microRNA (miR)-21 in systemic lupus erythematosus (SLE), and attempted to explore their association with clinical features. CD4 + T cells were isolated from peripheral blood of healthy donors and SLE patients by magnetic-activated cell sorting. GAS5 and miR-21 expression levels in cluster of differentiation (CD)4 + T cells were measured by reverse-transcription quantitative polymerase chain reaction. The results revealed that GAS5 and miR-21 levels were significantly elevated in CD4 + T cells of patients with SLE compared with those in control subjects (P<0.05). Regarding clinical features, SLE patients with ulceration had higher GAS5 expression levels in CD4 + T cells than those without ulceration (P<0.05), and the expression of miR-21 was significantly higher in CD4 + T cells of SLE patients with low levels of complement component 3 (C3) than in those with normal levels of complement C3 (P<0.05).In conclusion, GAS5 and miR-21 in CD4 + T cells may serve as potential biomarkers for the diagnosis and monitoring of the progression of SLE. IntroductionSystemic lu pus erythematosus (SLE) is a multisystemic, chronic inflammatory autoimmune disease of unknown etiology. It is characterized by various pathogenic autoantibodies and immune complexes as well as damage to multiple organ systems, and the course of SLE is long followed by remission and acute attack. The prevalence varies from 31-70/100,000 individuals in China and from 20-70/100,000 individuals worldwide. It is sex-associated, occurring nine times more often in women than in men, particularly in women of child-bearing age (15-35 years) (1-3). The interaction between certain genetic and environmental factors, including chemical factors, viruses and drugs, damages normal immune tolerance and contributes to SLE. Dysfunctional T cells interact with new antigens constantly, leading to a persistent autoimmune reaction (4,5). Previous studies have confirmed that the abnormal activation and proliferation of self-reactive cluster of differentiation (CD)4 + T lymphocytes have a central role in SLE. CD4 + T cells interact with antigen-specific B cells, to make the latter ones become more effective and produce autoantibodies. In addition, CD4 + T cells produce various cytokines when they are activated, which may engender inflammatory reactions (6,7).Long non-coding RNAs (lncRNAs) are a class of non-protein-coding RNA with transcripts longer than 200 nucleotides. They have numerous important biological functions through different molecular mechanisms, and are closely associated with a variety of clinical diseases, including tumors, metabolic disease and autoimmune diseases. Growth arrest-specific 5 (GAS5), a non-coding gene that hosts a number of small nucleolar RNAs, has been suggested to have numerous important roles in apoptosis and cell growth inhibition. Previous studies have reported that human GAS5 was upregulated in osteoarthritis (OA) patients (8) and downregulated i...

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“…Mouse lncRNA Gas5 is located on chromosome 1, with a length of 2554 bp. Recent studies have found that human serum lncRNA Gas5 level is correlated with T2DM[12]. However, it is unclear whether lncRNA Gas5 is involved in maintaining the function of adult mouse pancreatic β cells.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of Long Noncoding RNA Gas5 Affects Cell Cycle and Insulin Secretion in Mouse Pancreatic β Cells

Jin¹,

Wang

Zhu

et al. 2017

Cell Physiol Biochem

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Background: Evidence shows that long non-coding RNAs (lncRNAs) are involved in individual development, cell differentiation, cell cycle processes and other important life processes and are closely related to major human diseases, including diabetes. Recent studies have reported that lncRNAs are involved in β cell functions and that lncRNA Gas5 levels decreased in T2DM patients’ serum. The purpose of this study was to clarify the role of lncRNA Gas5 in mouse β cell functions in vitro and in vivo. Methods: lncRNA Gas5 expression in T2DM and normal mouse tissues was analyzed using qRT-PCR. RNAi, qRT-PCR, Annexin V-FITC assays, western blot, GSIS and RIA were performed to detect the effects of lncRNA Gas5 on insulin synthesis and secretion in vitro and in vivo. Results: The lncRNA Gas5 level was significantly decreased in db/db mice. However, lncRNA Gas5 expression was relatively high in the pancreas of normal mice. Knockdown of lncRNA Gas5 expression led to cell cycle G1 arrest and impaired insulin synthesis and secretion in Min6 cells. Further, knockdown of lncRNA Gas5 expression in primary isolated islets resulted in decreased expression of insulin gene and transcription factors, Pdx1 and MafA. These results indicate that lncRNA Gas5 might perform as a new regulator, maintaining β cell identity and function by affecting insulin synthesis and secretion.

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Circulating long noncoding RNA GAS5 levels are correlated to prevalence of type 2 diabetes mellitus

Cited by 145 publications

References 30 publications

Metformin-Induced Changes of the Coding Transcriptome and Non-Coding RNAs in the Livers of Non-Alcoholic Fatty Liver Disease Mice

Metformin-Induced Changes of the Coding Transcriptome and Non-Coding RNAs in the Livers of Non-Alcoholic Fatty Liver Disease Mice

Association of long non‑coding RNA GAS5 and miR‑21 levels in CD4+ T cells with clinical features of systemic lupus erythematosus

Downregulation of Long Noncoding RNA Gas5 Affects Cell Cycle and Insulin Secretion in Mouse Pancreatic β Cells

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