Long non-coding RNA metallothionein 1 pseudogene 3 promotes p2y12 expression by sponging miR-126 to activate platelet in diabetic animal model

Zhou, Ming; Gao, Meng; Luo, Yanwei; Gui, Rong; Ji, Hongwen

doi:10.1080/09537104.2018.1457781

Cited by 27 publications

(23 citation statements)

References 38 publications

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“…This receptor has an essential role in platelet activation (73). Zhou et al have shown that long non-coding RNA (lncRNA) metallothionein 1 pseudogene 3 (MT1P3), which is markedly upregulated in megakaryocytes of T2DM patients, enhances the expression of p2y12 receptor in platelets (74). They indicated that this is due to the inhibitory action of MT1P3 on miR-126.…”

Section: Effects Of T2dm On the Circulatory Systemmentioning

confidence: 99%

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

et al. 2020

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Metabolic abnormalities such as dyslipidemia, hyperinsulinemia, or insulin resistance and obesity play key roles in the induction and progression of type 2 diabetes mellitus (T2DM). The field of immunometabolism implies a bidirectional link between the immune system and metabolism, in which inflammation plays an essential role in the promotion of metabolic abnormalities (e.g., obesity and T2DM), and metabolic factors, in turn, regulate immune cell functions. Obesity as the main inducer of a systemic low-level inflammation is a main susceptibility factor for T2DM. Obesity-related immune cell infiltration, inflammation, and increased oxidative stress promote metabolic impairments in the insulin-sensitive tissues and finally, insulin resistance, organ failure, and premature aging occur. Hyperglycemia and the subsequent inflammation are the main causes of micro-and macroangiopathies in the circulatory system. They also promote the gut microbiota dysbiosis, increased intestinal permeability, and fatty liver disease. The impaired immune system together with metabolic imbalance also increases the susceptibility of patients to several pathogenic agents such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, the need for a proper immunization protocol among such patients is granted. The focus of the current review is to explore metabolic and immunological abnormalities affecting several organs of T2DM patients and explain the mechanisms, whereby diabetic patients become more susceptible to infectious diseases.

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Section: Effects Of T2dm On the Circulatory Systemmentioning

confidence: 99%

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

et al. 2020

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“…Long non-coding RNAs are a type of noncoding RNA, defined as being transcripts of more than 200 nucleotides in length, which cannot be translated into proteins (Peng et al, 2019). Excessive platelet activation is associated with an increased risk of thrombosis and there are few studies on the effects of lncRNAs on platelet activity (Zhou et al, 2019). In the current study, MEG-01 was activated with the platelet activator thrombin and it was discovered that the expression of NEAT1 was significantly increased.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Long Non-coding RNA Nuclear Paraspeckle Assembly Transcript 1 Inhibits MEG-01 Differentiation and Platelet-Like Particles Activity

et al. 2020

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Platelets are derived from megakaryocytes and play an important role in blood coagulation. By using high throughput sequencing, we have found that the long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) is abundant in platelets (GEO ID: 200097348). However, little is known about its role in regulating megakaryocyte differentiation and platelet activity. This study aims to clarify the effect of NEAT1 on MEG-01 differentiation and platelet-like particle (PLP) activity. NEAT1 in MEG-01 cells was knocked down by siRNA transfection. The adhesion of MEG-01 and PLP to collagen-coated coverslips was observed under a fluorescence microscope. Flow cytometry was used to investigate cell apoptosis, cell cycle, the levels of D41/CD42b on MEG-01 cells and CD62P on PLPs. Quantitative real-time polymerase chain reaction was used to detect NEAT1 and IL-8 expression levels. Western blot was used to measure the protein levels of Bcl-2, Bax, cleaved caspase-3, and IL-8. RNA-binding protein immunoprecipitation was used to detect the interaction of NEAT1 and splicing factor proline/glutamine-rich (SFPQ). Results showed that NEAT1 knockdown decreased the adhesion ability of thrombinstimulated MEG-01 and PLP. The expression of CD62P on PLPs and CD41/CD42b on MEG-01 cells was inhibited by NEAT1 knockdown. In addition, NEAT1 knockdown inhibited cell apoptosis with increased Bcl2/Bax ratio and decreased cleaved caspase-3, and reduced the percentage of cells in the G0/G1 phase. Meanwhile, NEAT1 knockdown inhibited the expression of IL-8. A strong interaction of NEAT1 and SFPQ, a transcriptional repressor of IL-8, was identified. NEAT1 knockdown reduced the interaction between SFPQ and NEAT1.The results suggest that lncRNA NEAT1 knockdown decreases MEG-01 differentiation, PLP activity, and IL-8 level. The results also indicate that the regulation of NEAT1 on IL-8 may be realized via a direct interaction between NEAT1 and SFPQ.

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“…In this context, the non-coding Metallothionein 1 Pseudogene 3 ( MT1P3 ) was found to be significantly upregulated in MKs from type 2 diabetes patients compared to healthy controls and, most importantly, had an impact on platelet activation and expression of the P2Y12 by sponging miR-126. Of note, depletion of MT1P3 by small interfering RNA (siRNA) reduced the expression of the ADP receptor, thereby inhibiting platelet activation and aggregation in a murine diabetes model [ 146 ].…”

Section: Role Of Non-coding Rnas In Megakaryopoiesis Platelet Biomentioning

confidence: 99%

Post-Transcriptional Expression Control in Platelet Biogenesis and Function

Neu

Gutschner

Haemmerle

2020

IJMS

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Platelets are highly abundant cell fragments of the peripheral blood that originate from megakaryocytes. Beside their well-known role in wound healing and hemostasis, they are emerging mediators of the immune response and implicated in a variety of pathophysiological conditions including cancer. Despite their anucleate nature, they harbor a diverse set of RNAs, which are subject to an active sorting mechanism from megakaryocytes into proplatelets and affect platelet biogenesis and function. However, sorting mechanisms are poorly understood, but RNA-binding proteins (RBPs) have been suggested to play a crucial role. Moreover, RBPs may regulate RNA translation and decay following platelet activation. In concert with other regulators, including microRNAs, long non-coding and circular RNAs, RBPs control multiple steps of the platelet life cycle. In this review, we will highlight the different RNA species within platelets and their impact on megakaryopoiesis, platelet biogenesis and platelet function. Additionally, we will focus on the currently known concepts of post-transcriptional control mechanisms important for RNA fate within platelets with a special emphasis on RBPs.

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Long non-coding RNA metallothionein 1 pseudogene 3 promotes p2y12 expression by sponging miR-126 to activate platelet in diabetic animal model

Cited by 27 publications

References 38 publications

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

Downregulation of Long Non-coding RNA Nuclear Paraspeckle Assembly Transcript 1 Inhibits MEG-01 Differentiation and Platelet-Like Particles Activity

Post-Transcriptional Expression Control in Platelet Biogenesis and Function

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