miR‐23b‐3p and miR‐125b‐5p downregulate apo(a) expression by targeting Ets1 in HepG2 cells

Zeng, Jie; Zeng, Zhaolin; Zhang, Kai; Zhao, Yue; Liu, Ya-mi; Chen, Jiaojiao; Hai, Tong; Wei, Dangheng; Jiang, Zhi‐Sheng; Wang, Zuo

doi:10.1002/cbin.10896

Cited by 16 publications

(12 citation statements)

References 31 publications

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“…Fourteen miRNAs were identified as atherosclerosis related in both models, including three previously reported miR-NAs that contribute to atherogenesis in different mechanisms of action. For example, miR-23b-3p has been shown to inhibit the synthesis of apo(a), one of the most important components of Lp(a), by targeting Ets1, increasing the risk of cardiovascular diseases (39). miR-30a-5p is correlated with calcification extension by targeting RUNX family transcription factor 2, and significantly upregulated in the arterial calcified culprit plaques of patients with acute coronary syndromes (40).…”

Section: Discussionmentioning

confidence: 99%

Hsa-miRNA-23a-3p promotes atherogenesis in a novel mouse model of atherosclerosis

Guo¹,

Mei²,

Sheng³

et al. 2020

Journal of Lipid Research

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Of the known regulators of atherosclerosis, miRNAs have been demonstrated to play critical roles in lipoprotein homeostasis and plaque formation. Here, we generated a novel animal model of atherosclerosis by knocking-in LDLRW483X in C57BL/6 mice, as the W483X mutation in LDLR is considered the most common, newly identified pathogenic mutation in Chinese familial hypercholesterolemia (FH) individuals. Using the new in vivo mouse model combined with a well-established atherosclerotic in vitro human cell model, we identified a novel atherosclerosis related miRNA, miR-23a-3p by microarray analysis of mouse aorta tissue specimens and human aorta endothelial cells (HAECs). MiR-23a-3p was consistently downregulated in both models, which was confirmed by qPCR. Bioinformatics analysis and further validation experiments revealed that the TNFAIP3 gene was the key target of miR-23a-3p. The miR-23a-3p-related functional pathways were then analysed in HAECs. Collectively, the present results suggest that miR-23a-3p regulates inflammatory and apoptotic pathways in atherogenesis by targeting TNFAIP3 through the NF-κB and p38/MAPK signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Hsa-miRNA-23a-3p promotes atherogenesis in a novel mouse model of atherosclerosis

Guo¹,

Mei²,

Sheng³

et al. 2020

Journal of Lipid Research

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“…Although it has been speculated that miR-23b-3p is also involved in fat metabolism, the conclusions are inconsistent. A study found that in HepG2 cells, miR-23b-3p inhibits the synthesis of ApoA protein, which is a risk factor for thrombotic diseases (Zeng et al, 2018), whereas another study reported that SIRT1, an enzyme that prevents lipid accumulation, was repressed by hsa-miR-23b-3p in hepatocytes (Borji et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Identification of key genes and long non-coding RNA associated ceRNA networks in hepatocellular carcinoma

Zhang

et al. 2019

PeerJ

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BackgroundHepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although multiple efforts have been made to understand the development of HCC, morbidity, and mortality rates remain high. In this study, we aimed to discover the mRNAs and long non-coding RNAs (lncRNAs) that contribute to the progression of HCC. We constructed a lncRNA-related competitive endogenous RNA (ceRNA) network to elucidate the molecular regulatory mechanism underlying HCC.MethodsA microarray dataset () containing information about both mRNAs and lncRNAs was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and lncRNAs (DElncRNAs) in tumor tissues and non-cancerous tissues were identified using the limma package of the R software. The miRNAs that are targeted by DElncRNAs were predicted using miRcode, while the target mRNAs of miRNAs were retrieved from miRDB, miRTarBas, and TargetScan. Functional annotation and pathway enrichment of DEGs were performed using the EnrichNet website. We constructed a protein–protein interaction (PPI) network of DEGs using STRING, and identified the hub genes using Cytoscape. Survival analysis of the hub genes and DElncRNAs was performed using the gene expression profiling interactive analysis database. The expression of molecules with prognostic values was validated on the UALCAN database. The hepatic expression of hub genes was examined using the Human Protein Atlas. The hub genes and DElncRNAs with prognostic values as well as the predictive miRNAs were selected to construct the ceRNA networks.ResultsWe found that 10 hub genes (KPNA2, MCM7, CKS2, KIF23, HMGB2, ZWINT, E2F1, MCM4, H2AFX, and EZH2) and four lncRNAs (FAM182B, SNHG6, SNHG1, and SNHG3) with prognostic values were overexpressed in the hepatic tumor samples. We also constructed a network containing 10 lncRNA–miRNA–mRNA pathways, which might be responsible for regulating the biological mechanisms underlying HCC.ConclusionWe found that the 10 significantly overexpressed hub genes and four lncRNAs were negatively correlated with the prognosis of HCC. Further, we suggest that lncRNA SNHG1 and the SNHG3-related ceRNAs can be potential research targets for exploring the molecular mechanisms of HCC.

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“…Moreover, the expression of miR‐125a‐5p is increased in hyperlipidemic (Simionescu, Niculescu, Sanda, Margina, & Sima, ). A previous study revealed that downregulation of apo(a) expression by miR‐125b‐5p by targeting Ets1 in HepG2 cells is related to As (J. F. Zeng, Zeng, et al, ). Nevertheless, whether miR‐125a‐5p is involved in VEC death upon oxLDL exposure and its relation to TET2 downregulation remain to be clarified.…”

Section: Introductionmentioning

confidence: 99%

OxLDL induces vascular endothelial cell pyroptosis through miR‐125a‐5p/TET2 pathway

Zeng

Chen

et al. 2018

Journal Cellular Physiology

110

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Pyroptosis participates in the formation and development of atherosclerosis (As) by promoting inflammatory factor release and is closely related to the stability of atherosclerotic plaque. MicroRNAs can regulate the expression of target genes at the posttranscriptional level. Previous studies have shown that miR-125a-5p increases in hyperlipidemic-hyperglycemic conditions and is involved in apoptosis, but its specific role in pyroptosis and As remains unclear. We propose that miR-125a-5p may be implicated in oxidized low-density lipoprotein (oxLDL)-induced vascular endothelial cells (VECs) pyroptosis and therefore conducted the current study. We observed that miR-125a-5p can inhibit tet methylcytosine dioxygenase 2 (TET2) expression at the posttranscription level, resulting in abnormal DNA methylation, mitochondrial dysfunction, and increased reactive oxygen species production, activated nuclear factor-κB that induces activation of inflammasome and maturation, release of proinflammatory cytokines interleukin (IL)-1β and IL-18, and pyroptosis. Given the role of VECs in vascular physiology, oxLDL-induced VEC pyroptosis may promote the development of As. Our current study reveals a novel pathway associated with pyroptosis program regulation, which comprises miR-125a-5p and TET2 in VECs.Modulation of their expression levels may serve as a potential target for therapeutic strategies of As. K E Y W O R D Satherosclerosis, miR-125a-5p, pyroptosis, ROS, TET2

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miR‐23b‐3p and miR‐125b‐5p downregulate apo(a) expression by targeting Ets1 in HepG2 cells

Cited by 16 publications

References 31 publications

Hsa-miRNA-23a-3p promotes atherogenesis in a novel mouse model of atherosclerosis

Hsa-miRNA-23a-3p promotes atherogenesis in a novel mouse model of atherosclerosis

Identification of key genes and long non-coding RNA associated ceRNA networks in hepatocellular carcinoma

OxLDL induces vascular endothelial cell pyroptosis through miR‐125a‐5p/TET2 pathway

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