Linking a role of lncRNAs (long non-coding RNAs) with insulin resistance, accelerated senescence, and inflammation in patients with type 2 diabetes
Abstract Background Studying epigenetics is expected to provide precious information on how environmental factors contribute to type 2 diabetes mellitus (T2DM) at the genomic level. With the progress of the whole-genome resequencing efforts, it is now known that 75–90% of the human genome was transc...
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| Format: | Article |
| Language: | English |
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BMC
2018-08-01
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| Series: | Human Genomics |
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| Online Access: | http://link.springer.com/article/10.1186/s40246-018-0173-3 |
| _version_ | 1811305997653770240 |
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| author | Chandrakumar Sathishkumar Paramasivam Prabu Viswanathan Mohan Muthuswamy Balasubramanyam |
| author_facet | Chandrakumar Sathishkumar Paramasivam Prabu Viswanathan Mohan Muthuswamy Balasubramanyam |
| author_sort | Chandrakumar Sathishkumar |
| collection | DOAJ |
| description | Abstract Background Studying epigenetics is expected to provide precious information on how environmental factors contribute to type 2 diabetes mellitus (T2DM) at the genomic level. With the progress of the whole-genome resequencing efforts, it is now known that 75–90% of the human genome was transcribed to generate a series of long non-coding RNAs (lncRNAs). While lncRNAs are gaining widespread attention as potential and robust biomarkers in the genesis as well as progression of several disease states, their clinical relevance and regulatory mechanisms are yet to be explored in the field of metabolic disorders including diabetes. Despite the fact that Asian Indians are highly insulin resistant and more prone to develop T2DM and associated vascular complications, there is virtually lack of data on the role of lncRNAs in the clinical diabetes setting. Therefore, we sought to evaluate a panel of lncRNAs and senescence-inflammation signatures in peripheral blood mononuclear cells (PBMCs) from patients with type 2 diabetes (T2DM; n = 30) compared to individuals with normal glucose tolerance (NGT; n = 32). Results Compared to control subjects, expression levels of lncRNAs in PBMCs from type 2 diabetes patients showed significantly (p < 0.05) increased levels of HOTAIR, MEG3, LET, MALAT1, MIAT, CDKN2BAS1/ANRIL, XIST, PANDA, GAS5, Linc-p21, ENST00000550337.1, PLUTO, and NBR2. In contrast, lncRNA expression patterns of THRIL and SALRNA1 were significantly (p < 0.05) decreased in patients with T2DM compared to control subjects. At the transcriptional level, senescence markers (p53, p21, p16, and β-galactosidase), proinflammatory markers (TNF-α, IL6, MCP1, and IL1-β), and epigenetic signature of histone deacetylase-3 (HDAC3) were significantly (p < 0.05) elevated in patients with type 2 diabetes compared to control subjects. Interestingly, mRNA expression of Sirt1 and telomere length were significantly (p < 0.05) decreased in patients with type 2 diabetes compared to control subjects. Majority of the altered lncRNAs were positively correlated with poor glycemic control, insulin resistance, transcriptional markers of senescence, inflammation, and HDAC3 and negatively correlated with telomere length. Logistic regression analysis revealed a significant association of altered lncRNA signatures with T2DM, but this association was lost after adjusting for insulin resistance (HOMA-IR) and senescence markers. Conclusion Our study provides a clinically relevant evidence for the association of altered lncRNAs with poor glycemic control, insulin resistance, accelerated cellular senescence, and inflammation. |
| first_indexed | 2024-04-13T08:36:30Z |
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| institution | Directory Open Access Journal |
| issn | 1479-7364 |
| language | English |
| last_indexed | 2024-04-13T08:36:30Z |
| publishDate | 2018-08-01 |
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| series | Human Genomics |
| spelling | doaj.art-3cbaf6c85def46f482247760bcca64c92022-12-22T02:54:04ZengBMCHuman Genomics1479-73642018-08-011211910.1186/s40246-018-0173-3Linking a role of lncRNAs (long non-coding RNAs) with insulin resistance, accelerated senescence, and inflammation in patients with type 2 diabetesChandrakumar Sathishkumar0Paramasivam Prabu1Viswanathan Mohan2Muthuswamy Balasubramanyam3Department of Cell and Molecular Biology and Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation and Dr. Mohan’s Diabetes Specialties Centre, GopalapuramDepartment of Cell and Molecular Biology and Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation and Dr. Mohan’s Diabetes Specialties Centre, GopalapuramDepartment of Cell and Molecular Biology and Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation and Dr. Mohan’s Diabetes Specialties Centre, GopalapuramDepartment of Cell and Molecular Biology and Dr. Rema Mohan High-Throughput Screening (HTS) Lab, Madras Diabetes Research Foundation and Dr. Mohan’s Diabetes Specialties Centre, GopalapuramAbstract Background Studying epigenetics is expected to provide precious information on how environmental factors contribute to type 2 diabetes mellitus (T2DM) at the genomic level. With the progress of the whole-genome resequencing efforts, it is now known that 75–90% of the human genome was transcribed to generate a series of long non-coding RNAs (lncRNAs). While lncRNAs are gaining widespread attention as potential and robust biomarkers in the genesis as well as progression of several disease states, their clinical relevance and regulatory mechanisms are yet to be explored in the field of metabolic disorders including diabetes. Despite the fact that Asian Indians are highly insulin resistant and more prone to develop T2DM and associated vascular complications, there is virtually lack of data on the role of lncRNAs in the clinical diabetes setting. Therefore, we sought to evaluate a panel of lncRNAs and senescence-inflammation signatures in peripheral blood mononuclear cells (PBMCs) from patients with type 2 diabetes (T2DM; n = 30) compared to individuals with normal glucose tolerance (NGT; n = 32). Results Compared to control subjects, expression levels of lncRNAs in PBMCs from type 2 diabetes patients showed significantly (p < 0.05) increased levels of HOTAIR, MEG3, LET, MALAT1, MIAT, CDKN2BAS1/ANRIL, XIST, PANDA, GAS5, Linc-p21, ENST00000550337.1, PLUTO, and NBR2. In contrast, lncRNA expression patterns of THRIL and SALRNA1 were significantly (p < 0.05) decreased in patients with T2DM compared to control subjects. At the transcriptional level, senescence markers (p53, p21, p16, and β-galactosidase), proinflammatory markers (TNF-α, IL6, MCP1, and IL1-β), and epigenetic signature of histone deacetylase-3 (HDAC3) were significantly (p < 0.05) elevated in patients with type 2 diabetes compared to control subjects. Interestingly, mRNA expression of Sirt1 and telomere length were significantly (p < 0.05) decreased in patients with type 2 diabetes compared to control subjects. Majority of the altered lncRNAs were positively correlated with poor glycemic control, insulin resistance, transcriptional markers of senescence, inflammation, and HDAC3 and negatively correlated with telomere length. Logistic regression analysis revealed a significant association of altered lncRNA signatures with T2DM, but this association was lost after adjusting for insulin resistance (HOMA-IR) and senescence markers. Conclusion Our study provides a clinically relevant evidence for the association of altered lncRNAs with poor glycemic control, insulin resistance, accelerated cellular senescence, and inflammation.http://link.springer.com/article/10.1186/s40246-018-0173-3lncRNASASPHDAC3Type 2 diabetesInsulin resistanceInflammation |
| spellingShingle | Chandrakumar Sathishkumar Paramasivam Prabu Viswanathan Mohan Muthuswamy Balasubramanyam Linking a role of lncRNAs (long non-coding RNAs) with insulin resistance, accelerated senescence, and inflammation in patients with type 2 diabetes Human Genomics lncRNA SASP HDAC3 Type 2 diabetes Insulin resistance Inflammation |
| title | Linking a role of lncRNAs (long non-coding RNAs) with insulin resistance, accelerated senescence, and inflammation in patients with type 2 diabetes |
| title_full | Linking a role of lncRNAs (long non-coding RNAs) with insulin resistance, accelerated senescence, and inflammation in patients with type 2 diabetes |
| title_fullStr | Linking a role of lncRNAs (long non-coding RNAs) with insulin resistance, accelerated senescence, and inflammation in patients with type 2 diabetes |
| title_full_unstemmed | Linking a role of lncRNAs (long non-coding RNAs) with insulin resistance, accelerated senescence, and inflammation in patients with type 2 diabetes |
| title_short | Linking a role of lncRNAs (long non-coding RNAs) with insulin resistance, accelerated senescence, and inflammation in patients with type 2 diabetes |
| title_sort | linking a role of lncrnas long non coding rnas with insulin resistance accelerated senescence and inflammation in patients with type 2 diabetes |
| topic | lncRNA SASP HDAC3 Type 2 diabetes Insulin resistance Inflammation |
| url | http://link.springer.com/article/10.1186/s40246-018-0173-3 |
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