NEAT1/hsa-miR-372–3p axis participates in rapamycin-induced lipid metabolic disorder

Zhao

Oxidative Medicine and Cellular Longevity

et al. 2022

Background. DCM is the most common and malignant complication of diabetes. It is characterized by myocardial dilatation, hypertrophy, fibrosis, ventricular remodeling, and contractile dysfunction. Although many studies have demonstrated the function of miRNAs in the progression of DCM, but the specific role of miR-372-3p in DCM remains unknown. Methods. C57/BL6J mice were used to construct mouse models of DCM by intraperitoneal injection of STZ (50 mg/kg/d) for 5 consecutive days. Then the mice were randomly divided into model group (intramyocardial injection of empty lentivirus) and miR-372-3p KD group (intramyocardial injection of miR-372-3p KD lentivirus at 10 9 /mouse). Besides, the control group (injection of 0.9% normal saline) was also set up. LY294002, a PI3K inhibitor, was employed in the current study. Western blotting, immunofluorescence staining, quantitative ultrasound method, Masson's trichrome staining, and bioinformatics analysis were performed. Results. It was found that miR-372-3p KD significantly improved left ventricular dysfunction and cardiac hypertrophy in DCM mice. Furthermore, it also improved myocardial interstitial fibrosis and remodeling in DCM mice. Immunofluorescence staining and RT-qPCR revealed that miR-372-3p KD might accelerate cardiac remodeling by increasing angiogenesis in DCM mice. Western blotting results revealed that miR-372-3p was an upstream target of the PI3K/ AKT-mTOR and HIF-1α signals, as well as NOX2, NOX4, which were responsible for angiogenesis in DCM mice. Besides, the in vitro experiment showed that LY294002 markedly diminished the increased expression levels of p-PI3K, AKT, p-mTOR, p-P70S6K, HIF-1α, NOX2, and NOX4 in the model group and the miR-372-3p KD group, suggesting that PI3K signaling pathway and oxidative stress are involved in miR-372-3p KD-induced angiogenesis in HG-stimulated C166 cells. Conclusions. MiR-372-3p KD inhibits the development of DCM via activating the PI3K/AKT/mTOR/HIF-1α signaling pathway or suppressing oxidative stress. This offers an applicable biomarker for DCM treatment.

Section: Discussionmentioning

confidence: 98%

“…Various studies have confirmed that miRNAs are beneficial diagnostic and therapeutic markers for controlling DCM [36]. As a crucial member of the miRNA family, miR-372-3p has been described to play a significant role in various diseases [37][38][39]. However, the specific function of miR-372-3p in DCM remains elusive.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of miR-372-3p Inhibits the Development of Diabetic Cardiomyopathy by Accelerating Angiogenesis via Activating the PI3K/AKT/mTOR/HIF-1α Signaling Pathway and Suppressing Oxidative Stress

Zhao

Oxidative Medicine and Cellular Longevity

et al. 2022

“… 136 Using rapamycin after transplantation can cause hypertriglyceridemia and liver triglyceride accumulation. 137 Fan et al indicated that the down-regulation of the expression of hsa-miR-372–3p contributes to triglyceride accumulation induced by rapamycin, further using dual-luciferase reporter assay and bioinformatics to determine the relationship between hsa-miR-372–3p and Neat1. 137 In vivo, Neat1 was upregulated in non-alcoholic fatty liver disease patients, and besides that, knockdown of Neat1 can inhibit lipid accumulation in mice with a high-fat diet.…”

Section: Neat1 Can Regulate the Expression Of Lipidsmentioning

confidence: 99%

“… 137 Fan et al indicated that the down-regulation of the expression of hsa-miR-372–3p contributes to triglyceride accumulation induced by rapamycin, further using dual-luciferase reporter assay and bioinformatics to determine the relationship between hsa-miR-372–3p and Neat1. 137 In vivo, Neat1 was upregulated in non-alcoholic fatty liver disease patients, and besides that, knockdown of Neat1 can inhibit lipid accumulation in mice with a high-fat diet. 138 Although Neat1 has been illustrated to be collectively effective in regulating lipids and inflammation, information regarding this aspect is scarce.…”

Section: Neat1 Can Regulate the Expression Of Lipidsmentioning

confidence: 99%

Novel Insights into the Emerging Role of Neat1 and Its Effects Downstream in the Regulation of Inflammation

Pan

Wang

Zhao

et al. 2022

JIR

Nuclear paraspeckle assembly transcript 1 (Neat1) located at chromosome 11 is a long non-coding RNA that is widely expressed in mammalian cell types, and which is overexpressed in several inflammation-related disorders. Inflammation implies a plethora of mutual interactions between both soluble factors and cells due to various stimuli including tissue injury. Although there is no doubt that inflammation is critically involved in multiple biological and pathological processes alike, the precise mechanisms being involved are still open for debate. In this context, the role of Neat1 as a regulator of inflammation, microglial activation, and lipid accumulation under various inflammatory conditions remains elusive. Herein, we review the regulation of Neat1 and how it modulates the expression of its target genes. Thereafter, we will review the impact of Neat1 on inflammation by activating or inhibiting various signaling pathways, such as microRNAs, AKT, TLR4, TRAF6, and NF-κB.

“…MYC can form a complex with kaposin B, which is another KSHV latent protein, to modulate the expression of a wide variety of host microRNAs [ 120 ], some of which, such as miR-210 [ 121 , 122 , 123 , 124 , 125 ], miR-3188 [ 126 ], miR-483-3p [ 127 ], miR-3197 [ 128 ], miR-423-5p [ 129 ], let-7f-5p [ 130 ], miR-372-3p [ 131 ], miR-9-5p [ 132 , 133 ], miR-489-3p [ 134 ], miR-1271-5p [ 135 ], miR-7-5p [ 136 ] miR-942-3p [ 137 ] and miR-153-3p [ 138 , 139 ], have been linked to metabolism in other diseases. In addition, the KSHV latent protein vIRF3 can stimulate the transcriptional activity of MYC by interacting with Skp2, a transcriptional cofactor that stabilizes and upregulates MYC activity [ 140 ].…”

Section: Regulation Of Myc By Dna Tumor Virus Oncoproteinsmentioning

confidence: 99%

Metabolic Control by DNA Tumor Virus-Encoded Proteins

Prusinkiewicz

Mymryk

2021

Pathogens

Viruses co-opt a multitude of host cell metabolic processes in order to meet the energy and substrate requirements for successful viral replication. However, due to their limited coding capacity, viruses must enact most, if not all, of these metabolic changes by influencing the function of available host cell regulatory proteins. Typically, certain viral proteins, some of which can function as viral oncoproteins, interact with these cellular regulatory proteins directly in order to effect changes in downstream metabolic pathways. This review highlights recent research into how four different DNA tumor viruses, namely human adenovirus, human papillomavirus, Epstein–Barr virus and Kaposi’s associated-sarcoma herpesvirus, can influence host cell metabolism through their interactions with either MYC, p53 or the pRb/E2F complex. Interestingly, some of these host cell regulators can be activated or inhibited by the same virus, depending on which viral oncoprotein is interacting with the regulatory protein. This review highlights how MYC, p53 and pRb/E2F regulate host cell metabolism, followed by an outline of how each of these DNA tumor viruses control their activities. Understanding how DNA tumor viruses regulate metabolism through viral oncoproteins could assist in the discovery or repurposing of metabolic inhibitors for antiviral therapy or treatment of virus-dependent cancers.