The novel regulatory role of lnc<scp>RNA</scp>‐mi<scp>RNA</scp>‐<scp>mRNA</scp> axis in cardiovascular diseases

Huang, Ying

doi:10.1111/jcmm.13866

Cited by 395 publications

(303 citation statements)

References 61 publications

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“…By inhibiting target mRNA translation or promoting mRNA degradation, miRNAs regulate many physiological and pathological processes 43 . Numerous studies have confirmed that microRNAs participate in the pathology of many cardiovascular diseases, such as cardiac remodeling, heart failure, myocardial damage, and DCM [43][44][45] . microRNAs could become potential therapeutic targets or prognostic indicators [43][44][45] .…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have confirmed that microRNAs participate in the pathology of many cardiovascular diseases, such as cardiac remodeling, heart failure, myocardial damage, and DCM [43][44][45] . microRNAs could become potential therapeutic targets or prognostic indicators [43][44][45] . Studies reported that miR-222 was negatively regulated in vascular smooth muscle cells and many cancer cell lines 30,46 .…”

Section: Discussionmentioning

confidence: 99%

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High-mobility group AT-hook 1 promotes cardiac dysfunction in diabetic cardiomyopathy via autophagy inhibition

Liu

Cai

et al. 2020

Cell Death Dis

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High-mobility group AT-hook1 (HMGA1, formerly HMG-I/Y), an architectural transcription factor, participates in a number of biological processes. However, its effect on cardiac remodeling (refer to cardiac inflammation, apoptosis and dysfunction) in diabetic cardiomyopathy remains largely indistinct. In this study, we found that HMGA1 was upregulated in diabetic mouse hearts and high-glucose-stimulated cardiomyocytes. Overexpression of HMGA1 accelerated high-glucose-induced cardiomyocyte inflammation and apoptosis, while HMGA1 knockdown relieved inflammation and apoptosis in cardiomyocytes in response to high glucose. Overexpression of HMGA1 in mice heart by adeno-associated virus 9 (AAV9) delivery system deteriorated the inflammatory response, increased apoptosis and accelerated cardiac dysfunction in streptozotocin-induced diabetic mouse model. Knockdown of HMGA1 by AAV9-shHMGA1 in vivo ameliorated cardiac remodeling in diabetic mice. Mechanistically, we found that HMGA1 inhibited the formation rather than the degradation of autophagy by regulating P27/CDK2/mTOR signaling. CDK2 knockdown or P27 overexpression blurred HMGA1 overexpression-induced deteriorating effects in vitro. P27 overexpression in mice heart counteracted HMGA1 overexpression-induced increased cardiac remodeling in diabetic mice. The luciferase reporter experiment confirmed that the regulatory effect of HMGA1 on P27 was mediated by miR-222. In addition, a miR-222 antagomir counteracted HMGA1 overexpression-induced deteriorating effects in vitro. Taken together, our data indicate that HMGA1 aggravates diabetic cardiomyopathy by directly regulating miR-222 promoter activity, which inhibits P27/mTOR-induced autophagy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

High-mobility group AT-hook 1 promotes cardiac dysfunction in diabetic cardiomyopathy via autophagy inhibition

Liu

Cai

et al. 2020

Cell Death Dis

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“…LncRNAs could serve as a kind of ceRNA to regulate target genes through interacting with miRNAs [23,24]. Recent studies have clarified that lncRNA-miRNA-mRNA form a novel regulatory network in various pathophysiological processes [25]. The role of MEG3 in cancers has been reported in several studies in which the interaction between lncRNAs, miR and mRNA, has been highlighted [26,27].…”

Section: Mmp1 Is Involved In Invasion and Metastasis During The Develmentioning

confidence: 99%

LncRNA MEG3 affects cell proliferation, apoptosis and migration by targeting miR-9-5p/MDK axis and activating PDK/AKT pathway in hepatocellular carcinoma

Wu¹,

Ma²,

Ma³

et al. 2020

Preprint

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KEYWORDShepatocellular carcinoma, lncRNA MEG3, miR-9-5p, MDK, PDK/AKT pathway 2 Abstract Background Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) was supposed to be a tumor suppressor in various cancers. However, the role of MEG3 in hepatocellular carcinoma (HCC) and the related molecular mechanisms are not well illustrated. This study aimed to determine the biological function of MEG3 in regulating HCC cell proliferation, apoptosis and migration. Moreover, the interaction among MEG3, microRNA (miR)-9-5p and Midkine (MDK), and the activation of phosphoinositide-dependent kinase (PDK)/AKT pathway in HCC cells were examined. Methods and ResultsExpression of MEG3 in a series of liver cancer cell lines was detected by RT-qPCR. Luciferase reporter assay, RT-qPCR and western blot were used to determine the interaction among MEG3, miR-9-5p and MDK, and the activation of PDK/AKT pathway. Cell proliferation and apoptosis were evaluated by CCK8, flow cytometry analysis for cell cycle and apoptosis, and Caspase 3/9 activity. Cell migration was determined by wound healing assay and MMP1 expression. We found MEG3 was decreased in HCC cell lines compared with the normal liver cell line. MEG3 suppressed HCC cell proliferation and migration, and induced cell apoptosis. Further, we found MEG3 targets miR-9-5p/MDK axis and modulates PDK/AKT pathway in HCC. ConclusionOur findings demonstrated that lncRNA MEG3 affects HCC cell proliferation, apoptosis and migration through its targeting of miR-9-5p/MDK and regulating of PDK/AKT pathway. This study suggested MEG3/miR-9-5p/MDK axis as the potential therapeutic target in HCC.

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“…Emerging evidence has indicated that ncRNAs, constituting a vast majority of the human transcriptome and previously considered as non-functional (7), could also regulate gene expression and are involved in the progression of a variety of cancers (8)(9)(10). As an important component of ncRNAs, microRNA could regulate oncogenesis and tumor progression by either blocking mRNA translation or promoting mRNA degradation (11,12). We previously confirmed that microRNA-637 (miR-637) is a favorable prognosis marker in glioma that targets the 3ʹ-untranslated region (UTR) of Akt1 (13).…”

Section: Introductionmentioning

confidence: 99%

Oncogenic ZEB2/miR-637/HMGA1 signaling axis targeting vimentin promotes the malignant phenotype of glioma

Zeng

Que

Lin

et al. 2020

Preprint

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Background Glioma is the most common primary tumor of the central nervous system. We previously confirmed that zinc finger E-box binding homeobox (ZEB) 2 promotes the malignant progression of glioma, while microRNA-637 (miR-637) is associated with favorable prognosis in glioma. This study investigated the potential interaction between ZEB2 and miR-637 and its downstream signaling pathway in glioma. Methods Chromatin immunoprecipitation, luciferase reporter, and electrophoretic mobility shift assays were used to confirm ZEB2 binding to miR-637. Microarray and bioinformatic analyses were used to investigate targets of miR-637. MTT and EdU assays, transwell assays, and Boyden assays were utilized to assess cell viability, migration, and invasion, respectively. A subcutaneous xenograft model was utilized for analyzing the role of miR-637/high mobility group A1 (HMGA1) interaction in vivo. Immunohistochemistry staining of clinical samples and bioinformatic analysis of the Chinese Glioma Genome Atlas and The Cancer Genome Atlas databases were performed to further confirm the ZEB2/miR-637/HMGA1/vimentin axis. Results ZEB2 was bound directly bind to the E-box elements in the miR-637 promoter and promoted cell proliferation, migration, and invasion via miR-637 downregulation. Subsequent screening confirmed that HMGA1 was a direct target of miR-637, while miR-637 could propagate the malignant phenotype of glioma by suppressing HMGA1 both in vitro and in vivo. Furthermore, the interaction between cytoplasmic HMGA1 and vimentin was observed, and vimentin inhibition could abolish increased migration and invasion induced by HMGA1 overexpression. Notably, the ZEB2/miR-637/HMGA1/vimentin axis was also evident in glioma tissue samples and public glioma datasets, while both HMGA1 and vimentin were associated with an unfavorable prognosis in glioma. Additionally, upregulated HMGA1 and vimentin were found in isocitrate dehydrogenase (IDH) wild-type and 1p/19q non-codeletion diffusely infiltrating glioma. Conclusions We identified an oncogenic ZEB2/miR-637/HMGA1 signaling axis targeting vimentin that promotes both migration and invasion in glioma. This not only extends the current understanding of miR-637 regulation in glioma, but also unravels a novel signaling pathway that integrates a transcriptional factor, microRNA, and a chromatin remodeling factor to modulate the malignant phenotype of glioma.

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The novel regulatory role of lncRNA‐miRNA‐mRNA axis in cardiovascular diseases

Cited by 395 publications

References 61 publications

High-mobility group AT-hook 1 promotes cardiac dysfunction in diabetic cardiomyopathy via autophagy inhibition

High-mobility group AT-hook 1 promotes cardiac dysfunction in diabetic cardiomyopathy via autophagy inhibition

LncRNA MEG3 affects cell proliferation, apoptosis and migration by targeting miR-9-5p/MDK axis and activating PDK/AKT pathway in hepatocellular carcinoma

Oncogenic ZEB2/miR-637/HMGA1 signaling axis targeting vimentin promotes the malignant phenotype of glioma

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