&lt;p&gt;Role of miRNA-424 in Cancers&lt;/p&gt;

Li, Shu-Lin; Wu, Yuqi; Zhang, Jiawei; Sun, Hao; Wang, Xiangwei

doi:10.2147/ott.s266541

Cited by 16 publications

(14 citation statements)

References 103 publications

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“…Thus, they are widely implicated in many disorders such as cardiovascular disease, neural disease, and cancer. 59,60 During heart development, miR-322/miR-503 has been shown to drive early cardiac progenitor cells toward cardiomyocyte lineage, although the underlying mechanism is undetermined. 61 Our current study demonstrates that HDAC3 represses miR-322 and miR-503 expression to induce the expression of several major growth ligands including FGF9 and IGF2 for ventricular wall cardiomyocyte proliferation (Figure 7F).…”

Section: Discussionmentioning

confidence: 99%

Epicardial HDAC3 Promotes Myocardial Growth Through a Novel MicroRNA Pathway

Jang

Song

Pettit

et al. 2022

Circulation Research

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BACKGROUND: Establishment of the myocardial wall requires proper growth cues from nonmyocardial tissues. During heart development, the epicardium and epicardium-derived cells instruct myocardial growth by secreting essential factors including FGF (fibroblast growth factor) 9 and IGF (insulin-like growth factor) 2. However, it is poorly understood how the epicardial secreted factors are regulated, in particular by chromatin modifications for myocardial formation. The current study is to investigate whether and how HDAC (histone deacetylase) 3 in the developing epicardium regulates myocardial growth. METHODS AND RESULTS: We deleted Hdac3 in the developing murine epicardium, and mutant hearts showed ventricular myocardial wall hypoplasia with reduction of epicardium-derived cells. The cultured embryonic cardiomyocytes with supernatants from Hdac3 knockout (KO) mouse epicardial cells also showed decreased proliferation. Genome-wide transcriptomic analysis revealed that Fgf9 and Igf2 were significantly downregulated in Hdac3 KO mouse epicardial cells. We further found that Fgf9 and Igf2 expression is dependent on HDAC3 deacetylase activity. The supplementation of FGF9 or IGF2 can rescue the myocardial proliferation defects treated by Hdac3 KO supernatant. Mechanistically, we identified that microRNA (miR)-322 and miR-503 were upregulated in Hdac3 KO mouse epicardial cells and Hdac3 epicardial KO hearts. Overexpression of miR-322 or miR-503 repressed FGF9 and IGF2 expression, while knockdown of miR-322 or miR-503 restored FGF9 and IGF2 expression in Hdac3 KO mouse epicardial cells. CONCLUSIONS: Our findings reveal a critical signaling pathway in which epicardial HDAC3 promotes compact myocardial growth by stimulating FGF9 and IGF2 through repressing miR-322 or miR-503, providing novel insights in elucidating the etiology of congenital heart defects and conceptual strategies to promote myocardial regeneration.

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Section: Discussionmentioning

confidence: 99%

Epicardial HDAC3 Promotes Myocardial Growth Through a Novel MicroRNA Pathway

Jang

Song

Pettit

et al. 2022

Circulation Research

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“…miRNA is related to many biological functions, such as proliferation, development, differentiation, apoptosis, and metabolism [ 12 ]. Many studies showed that abnormal miRNA expression is significantly linked to tumorigenesis, and it is now a hot research area [ 13 , 14 ]. The most prevalent subtype of lung cancer is adenocarcinoma, which has a high worldwide morbidity and mortality rate [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Six MicroRNA Prognostic Models for Overall Survival of Lung Adenocarcinoma

Gao

et al. 2022

Genetics Research

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Objective. The purpose of this study is to screen for microRNAs (miRNAs) associated with the prognosis of lung adenocarcinoma (LUAD) and to explore its prognosis and effects on the tumor microenvironment in patients with LUAD. Methods. Gene expression data, miRNA expression data, and clinical data for two different databases, TCGA-LUAD and CPTAC-3 LUAD, were downloaded from the GDC database. The miRNA prognosis of LUAD was filtered by the Cox proportional hazard model and the Least Absolute Shrinkage and Selection Operator (LASSO) regression model. The performance of the model was validated by time-dependent receiver operating characteristics (ROC) curves. Possible biological processes associated with the miRNAs target gene were analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, the prognostic model was scored by risk, divided into high- and low-risk groups by median, and the differences in the immersion level of 21 immune cells in the high- and low-risk groups were assessed. To gain a deeper understanding of the underlying mechanism behind the model, the two most important miRNAs in the model, miR-195-3p and miR-5571-5p, were selected for HPA database validation and ceRNA network construction. Results. Of the 209 variance expressions identified in the screening analysis, 145 were upregulated and 64 were downregulated by miRNAs. The prognostic models of six miRNA genes were obtained: miR-195-3p, miR-5571-5p, miR-584-3p, miR-494-3p, miR-4664-3p, and miR-1293. These six genes were significantly associated with survival rates in LUAD patients. In particular, miR-1293, miR-195-3p, and miR-5571-5p are highly correlated with OS. The higher expression of miR-195-3p and miR-5571-5p, the better survival of LUAD OS is, and these two miRNA expressions contribute the most to the model. Finally, after sorting the risk scores calculated from low to high using the prognostic model, the patients with higher scores had shorter survival time and higher frequency of death, and there were significant differences in the immersion levels of 21 immune cells in the high- and low-risk groups. ceRNA network analysis found that TM9SF3 was regulated by miR-195-3p and was highly expressed in the tissues of LUAD patients, and the prognosis of the patients was poor. Conclusions. miR-195-3p, miR-5571-5p, miR-584-3p, miR-494-3p, miR-4664-3p, and miR-1293 may be used as new biomarkers for prognosis prediction of LUAD. Our results also identified a lncRNA MEG3/miR-195-3p/RAB1A/TM9SF3 regulatory axis, which may also play an important role in the progression of LUAD. Further study needs to be conducted to verify this result.

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“…miR-322 and miR-503 regulate many fundamental processes such as cell proliferation, death, differentiation, metabolism, and stress response. Thus, they are widely implicated in many disorders such as cardiovascular disease, neural disease, and cancer 71,72 . During heart development, miR-322/miR-503 has been shown to drive early cardiac progenitor cells toward cardiomyocyte lineage, although the underlying mechanism is undetermined 73 .…”

Section: Discussionmentioning

confidence: 99%

Epicardial HDAC3 promotes myocardial growth through a novel microRNA pathway

Jang

Song

et al. 2021

Preprint

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Rational: Establishment of the myocardial wall requires proper growth cues from nonmyocardial tissues. During heart development, the epicardium and epicardium-derived cells (EPDCs) instruct myocardial growth by secreting essential factors including fibroblast growth factor 9 (FGF9) and insulin-like growth factor 2 (IGF2). However, it is poorly understood how the epicardial secreted factors are regulated, in particular by chromatin modifications for myocardial formation. Objective: To understand whether and how histone deacetylase 3 (HDAC3) in the developing epicardium regulates myocardial growth. Methods and Results: We deleted Hdac3 in the developing murine epicardium and mutant hearts showed ventricular myocardial wall hypoplasia with reduction of EPDCs. The cultured embryonic cardiomyocytes with supernatants from Hdac3 knockout (KO) mouse epicardial cells (MECs) also showed decreased proliferation. Genome-wide transcriptomic analysis revealed that Fgf9 and Igf2 were significantly down-regulated in Hdac3 KO MECs. We further found that Fgf9 and Igf2 expression is dependent on HDAC3 deacetylase activity. The supplementation of FGF9 or IGF2 can rescue the myocardial proliferation defects treated by Hdac3 KO supernatant. Mechanistically, we identified that microRNA (miR)-322 and miR-503 were upregulated in Hdac3 KO MECs and Hdac3 epicardial KO hearts. Overexpression of miR-322 or miR-503 repressed FGF9 and IGF2 expression, while knockdown of miR-322 or miR-503 restored FGF9 and IGF2 expression in Hdac3 KO MECs. Conclusions: Our findings reveal a critical signaling pathway in which epicardial HDAC3 promotes compact myocardial growth by stimulating FGF9 and IGF2 through repressing miR-322/miR-503, providing novel insights in elucidating etiology of congenital heart defects, and conceptual strategies to promote myocardial regeneration.

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<p>Role of miRNA-424 in Cancers</p>

Cited by 16 publications

References 103 publications

Epicardial HDAC3 Promotes Myocardial Growth Through a Novel MicroRNA Pathway

Epicardial HDAC3 Promotes Myocardial Growth Through a Novel MicroRNA Pathway

Six MicroRNA Prognostic Models for Overall Survival of Lung Adenocarcinoma

Epicardial HDAC3 promotes myocardial growth through a novel microRNA pathway

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