Diagnostic significance of serum lncRNA HOTAIR and its predictive value for the development of chronic complications in patients with type 2 diabetes mellitus

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Abstract

Background

Type 2 diabetes mellitus (T2DM) affects the social economy and quality of life, and has become a major threat to human health. This observation aimed to study the possibility of serum HOTAIR as a diagnostic index in patients with T2DM and to explore the prognostic potential of HOTAIR in the development of T2DM.

Methods

The expression of HOTAIR in serum of 96 patients with T2DM and 82 healthy controls was detected by the qRT-PCR technique. The related biochemical indexes of all participants were determined, such as total cholesterol (TC) and fasting blood glucose (FBG). The value of serum HOTAIR in the diagnosis of T2DM in the two groups was analyzed by the ROC curve. Moreover, the prognostic value of HOTAIR on T2DM was examined by the K-M curve and COX multivariate analysis.

Results

The results of the qRT-PCR analysis showed that the serum level of HOTAIR in patients with T2DM was significantly higher than that in healthy controls. ROC analysis showed that HOTAIR in serum was a diagnostic factor of T2DM. Further multivariate analysis showed that HOTAIR could be an independent biomarker in the prediction of chronic complications for T2DM patients, such as diabetic retinopathy and diabetic nephropathy.

Conclusions

We found the augment of HOTAIR expression was a character of T2DM. The high expression of serum HOTAIR was a potential non-invasive diagnostic marker and independent prognostic factor in patients with T2DM.

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Most cited references 36

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LncRNA HOTAIR: A master regulator of chromatin dynamics and cancer.

Arunoday Bhan, Subhrangsu Mandal (2015)

Non-coding RNAs (ncRNAs) are emerging classes of regulatory RNA that play key roles in various cellular and physiological processes such as in gene regulation, chromatin dynamics, cell differentiation, and development. NcRNAs are dysregulated in a variety of human disorders including cancers, neurological disorders, and immunological disorders. The mechanisms through which ncRNAs regulate various biological processes and human diseases still remain elusive. HOX antisense intergenic RNA (HOTAIR) is a recently discovered long non-coding RNA (lncRNA) that plays critical role in gene regulation and chromatin dynamics, appears to be misregulated in a variety of cancers. HOTAIR interacts with key epigenetic regulators such as histone methyltransferase PRC2 and histone demethylase LSD1 and regulates gene silencing. Here, we have reviewed recent advancements in understanding the functions and regulation of HOTAIR and its association with cancer and other diseases.

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Linking a role of lncRNAs (long non-coding RNAs) with insulin resistance, accelerated senescence, and inflammation in patients with type 2 diabetes

Chandrakumar Sathishkumar, Paramasivam Prabu, Viswanathan Mohan … (2018)

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. Electronic supplementary material The online version of this article (10.1186/s40246-018-0173-3) contains supplementary material, which is available to authorized users.

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MALAT1 as a Diagnostic and Therapeutic Target in Diabetes-Related Complications: A Promising Long-Noncoding RNA

Leila Abdulle, Ji-long Hao, Om Pant … (2019)

Diabetes mellitus is a global issue with increasing incidence rate worldwide. In an uncontrolled case, it can advance to various organ-related complications leading to an increase in morbidity and mortality. Long non-coding RNA (lncRNA) Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) appears to be a fairly novel lncRNA that is relevant to diabetes and its role in diabetic-related diseases initiation and progression have long been a subject of attention to many scholars. The expression of MALAT1 is elevated in different diabetic-related diseases. In this review, we demonstrate the various functions of MALAT1 in the different diabetes-related complications including ischemic reperfusion injury, retinopathy, cataract, atherosclerosis, cardiomyopathy, non-alcoholic steatohepatitis, gastroparesis, kidney disease, and gestational diabetes. The emerging evidence showed that the role of MALAT1 in diabetic-related complications is both pro-inflammatory and apoptosis in different cell types. These results concluded that MALAT1 is a potential diagnostic and future targeted therapy for diabetes-associated complications.