MicroRNA regulation in hypoxic environments: differential expression of microRNAs in the liver of largemouth bass (Micropterus salmoides)

Sun, Jun; Zhao, Ling; He, Kuo; Li, Qiao; Luo, Jie; Zhang, Dong Mei; Ji, Liang; Liao, Lei; Deng, Ji

doi:10.1007/s10695-020-00877-7

Cited by 13 publications

(6 citation statements)

References 75 publications

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“…Moreover, another study discovered increased IP6K gene expression in largemouth bass exposed to hypoxic conditions. [52] Hence, 5-PP-InsP 5 might be part of the cellular machinery that mediates the metabolic adaptation to reduced p[O 2 ].…”

Section: Resultsmentioning

confidence: 99%

β-Lapachone Regulates Mammalian Inositol Pyrophosphate Levels in an NQO1- and Oxygen-dependent Manner

Eisenbeis

Qiu

Strotmann

et al. 2022

Preprint

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Inositol pyrophosphates (PP-InsPs) are energetic signalling molecules with important functions in mammals. As their biosynthesis depends on ATP concentration, PP InsPs are tightly connected to cellular energy homeostasis. Consequently, an increasing number of studies involves PP InsPs in metabolic disorders, such as type 2 diabetes, aspects of tumorigenesis, and hyperphosphatemia. Research conducted in yeast suggests that the PP InsP pathway is activated in response to reactive oxygen species (ROS). However, the precise modulation of PP InsPs during cellular ROS signalling is unknown. Here, we report how mammalian PP InsP levels are changing during exposure to exogenous (H2O2) and endogenous ROS. Using capillary electrophoresis electrospray ionization mass spectrometry (CE-ESI MS), we found that PP-InsP levels decrease upon exposure to oxidative stressors in HCT116 cells. Application of quinone drugs, particularly β-lapachone (β-lap), under normoxic and hypoxic conditions enabled us to produce ROS in cellulo and to show that β lap treatment caused PP-InsP changes that are oxygen dependent. Experiments in MDA-MB-231 breast cancer cells deficient of NAD(P)H:quinone oxidoreductase-1 (NQO1) demonstrated that β-lap requires NQO1-bioactivation to regulate the cellular metabolism of PP InsPs. Critically, significant reductions in cellular ATP concentrations were not directly mirrored in reduced PP InsP levels as shown in NQO1-deficient MDA-MB-231 cells treated with β-lap. The data presented here unveil new aspects of β-lap pharmacology and its impact on PP-InsP levels. Our identification of different quinone drugs as modulators of PP-InsP synthesis will allow to better appreciate their overall impact on cellular function.

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Section: Resultsmentioning

confidence: 99%

β-Lapachone Regulates Mammalian Inositol Pyrophosphate Levels in an NQO1- and Oxygen-dependent Manner

Eisenbeis

Qiu

Strotmann

et al. 2022

Preprint

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“…In this way, changes in miR-20a-3p and other miRNAs could help enhance survival of HIV in the host and have a secondary consequence of metabolic complications. In addition, miR-20a-3p has also been implicated in the MAPK signaling pathway and phosphatidylinositol signaling system ( 28 ). Consistent with the current study, miRNA-20a-3p has been shown to be elevated among patients with type 2 diabetes mellitus compared with healthy individuals when isolated from circulating plasma ectosomes ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

Altered pattern of circulating miRNAs in HIV lipodystrophy perturbs key adipose differentiation and inflammation pathways

Srinivasa¹,

García‐Martín²,

Torriani³

et al. 2021

JCI Insight

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We identified a microRNA (miRNA) profile characterizing HIV lipodystrophy and explored the downstream mechanistic implications with respect to adipocyte biology and the associated clinical phenotype. miRNA profiles were extracted from small extracellular vesicles (sEVs) of HIV-infected individuals with and without lipodystrophic changes and individuals without HIV, among whom we previously showed significant reductions in adipose Dicer expression related to HIV. miR-20a-3p was increased and miR-324-5p and miR-186 were reduced in sEVs from HIV lipodystrophic individuals. Changes in these miRNAs correlated with adipose Dicer expression and clinical markers of lipodystrophy, including fat redistribution, insulin resistance, and hypertriglyceridemia. Human preadipocytes transfected with mimic miR-20a-3p, anti–miR-324-5p, or anti–miR-186 induced consistent changes in latent transforming growth factor beta binding protein 2 ( Ltbp2 ), Wisp2 , and Nebl expression. Knockdown of Ltbp2 downregulated markers of adipocyte differentiation ( Fabp4 , Ppar γ, C/ebpa , Fasn , adiponectin , Glut4 , CD36 ), and Lamin C , and increased expression of genes involved in inflammation ( IL1 β , IL6 , and Ccl20 ). Our studies suggest a likely unique sEV miRNA signature related to dysregulation of Dicer in adipose tissue in HIV. Enhanced miR-20a-3p or depletion of miR-186 and miR-324-5p may downregulate Ltbp2 in HIV, leading to dysregulation in adipose differentiation and inflammation, which could contribute to acquired HIV lipodystrophy and associated metabolic and inflammatory perturbations.

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“…Among the 22 differentially expressed miRNAs identified by NGS, miR-106a-5p, miR-574-3p, and miR-145-5p have been shown to be dysregulated in OSA patients in previous studies, while miR-26b-3p, miR-15b-5p, miR-16-5p, miR-29c-5p, miR-145-5p, miR-133a, and miR-223 gene expressions found to be skewed in response to IHR stimuli in vitro or in animal models [ 30 , 31 , 32 ]. In accordance with our findings, miR-145-5p has been demonstrated to be down-regulated in OSA patients and protect animals from aortic remodeling through targeting Smad3 in chronic intermittent hypoxic canine models [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Sequencing Analysis in Obstructive Sleep Apnea and Depression: Anti-Oxidant and MAOA-Inhibiting Effects of miR-15b-5p and miR-92b-3p through Targeting PTGS1-NF-κB-SP1 Signaling

Chen

Hsu

et al. 2021

Antioxidants

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The aim of this study was to identify novel microRNAs related to obstructive sleep apnea (OSA) characterized by intermittent hypoxia with re-oxygenation (IHR) injury. Illumina MiSeq was used to identify OSA-associated microRNAs, which were validated in an independent cohort. The interaction between candidate microRNA and target genes was detected in the human THP-1, HUVEC, and SH-SY5Y cell lines. Next-generation sequencing analysis identified 22 differentially expressed miRs (12 up-regulated and 10 down-regulated) in OSA patients. Enriched predicted target pathways included senescence, adherens junction, and AGE-RAGE/TNF-α/HIF-1α signaling. In the validation cohort, miR-92b-3p and miR-15b-5p gene expressions were decreased in OSA patients, and negatively correlated with an apnea hypopnea index. PTGS1 (COX1) gene expression was increased in OSA patients, especially in those with depression. Transfection with miR-15b-5p/miR-92b-3p mimic in vitro reversed IHR-induced early apoptosis, reactive oxygen species production, MAOA hyperactivity, and up-regulations of their predicted target genes, including PTGS1, ADRB1, GABRB2, GARG1, LEP, TNFSF13B, VEGFA, and CXCL5. The luciferase assay revealed the suppressed PTGS1 expression by miR-92b-3p. Down-regulated miR-15b-5p/miR-92b-3p in OSA patients could contribute to IHR-induced oxidative stress and MAOA hyperactivity through the eicosanoid inflammatory pathway via directly targeting PTGS1-NF-κB-SP1 signaling. Over-expression of the miR-15b-5p/miR-92b-3p may be a new therapeutic strategy for OSA-related depression.

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MicroRNA regulation in hypoxic environments: differential expression of microRNAs in the liver of largemouth bass (Micropterus salmoides)

Cited by 13 publications

References 75 publications

β-Lapachone Regulates Mammalian Inositol Pyrophosphate Levels in an NQO1- and Oxygen-dependent Manner

β-Lapachone Regulates Mammalian Inositol Pyrophosphate Levels in an NQO1- and Oxygen-dependent Manner

Altered pattern of circulating miRNAs in HIV lipodystrophy perturbs key adipose differentiation and inflammation pathways

MicroRNA Sequencing Analysis in Obstructive Sleep Apnea and Depression: Anti-Oxidant and MAOA-Inhibiting Effects of miR-15b-5p and miR-92b-3p through Targeting PTGS1-NF-κB-SP1 Signaling

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