MicroRNA-224 down-regulates Glycine N-methyltransferase gene expression in Hepatocellular Carcinoma

Hung, Jan Jong; Li, Chung Hsien; Yeh, Ching‐Hua; Huang, Pin Cheng; Fang, Cheng; Chen, Yen-Fu; Lee, Kuo Jui; Chou, Chih‐Hung; Cheng, Hsin Yun; Huang, Hsien Da; Chen, Marcelo; Tsai, Ting Fen; Lin, Anya Maan Yuh; Yen, Chia-Hung; Tsou, Ann-Ping; Tyan, Yu‐Chang; Chen, Yi Ming Arthur

doi:10.1038/s41598-018-30682-5

Cited by 22 publications

(14 citation statements)

References 61 publications

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“…Also, MiR-224 has a role in the development and progression of HCC in light of the way that it tethers to 3′UTR regions of the genes that are engaged in the process of cell apoptosis, proliferation, and invasion (Ma et al, 2012;Zhang et al, 2013;Li et al, 2014;Hung et al, 2018).…”

Section: Research Articlementioning

confidence: 99%

Diagnostic Performance of microRNA-122 and microRNA-224 in Hepatitis C Virus-Induced Hepatocellular Carcinoma (HCC)

Shehab-Eldeen

Nada

Abou-Elela

et al. 2019

Asian Pac J Cancer Prev

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Background and objectives: Hepatocellular carcinoma (HCC) is a potential health problem in Egypt because of the high prevalence of HCV infection. Using alpha-fetoprotein for diagnosis is unsatisfactory especially in early stages. Many studies showed that microRNAs (miRNA) expression may be associated with the development and progression of various types of cancer including HCC and it may serve as biomarkers for diagnosis. This study examined two miRNAs which are miRNA-122 and miRNA-224 if it could serve as biomarkers for diagnosis of HCC. Methods: This study included 20 patients with HCV-induced HCC and 20 patients with HCV-induced liver cirrhosis for comparison. As well as 20 healthy volunteers as controls. All participants were subjected to history taking, clinical examination, and determination of serum alpha-fetoprotein. Quantification of plasma miRNA-122 and miRNA-224 was done by real-time quantitative PCR. Results: Our results showed that levels of miRNA-122 were significantly lower in HCC group compared to the cirrhosis group and controls, while levels of miRNA-224 were significantly higher. The levels of both miRNAs have a correlation with tumor size. Moreover, the diagnostic accuracy of miRNA-122 (sensitivity 95%, specificity 81%, p-value <0.001) and of miRNA-224 (sensitivity 85%, specificity 79%, p-value <0.001) in discriminating patients with HCC from patients with liver cirrhosis were higher than that of alpha-fetoprotein (sensitivity 70%, specificity 70%, p-value <0.05). In addition, combining any one of these miRNAs with alpha-fetoprotein will increase the diagnostic accuracy compared to using each marker alone. Conclusion: miRNA-122 and miRNA-224 could serve as biomarkers for the diagnosis of HCC.

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Section: Research Articlementioning

confidence: 99%

Diagnostic Performance of microRNA-122 and microRNA-224 in Hepatitis C Virus-Induced Hepatocellular Carcinoma (HCC)

Shehab-Eldeen

Nada

Abou-Elela

et al. 2019

Asian Pac J Cancer Prev

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“…According to the study of Li et al [10], miR-224 was vital for celastrol-stimulated repression of HCC cell invasion and migration. Besides, on the basis of binding to 3′ UTR regions of certain genes, miR-224 was associated with HCC cell proliferation, migration, and so on [11, 12]. Through targeting PPP2R1B, miR-224 accelerated cell proliferation, migration, and invasion of HCC cells [13].…”

Section: Introductionmentioning

confidence: 99%

“…Through targeting PPP2R1B, miR-224 accelerated cell proliferation, migration, and invasion of HCC cells [13]. During liver tumorigenesis, miR-224 had a momentous effect in the repression of glycine N -methyltransferase and could target the mRNA coding sequence of glycine N -methyltransferase [11]. Gene regulatory networks are complex, and one miRNA may regulate multiple genes [14, 15].…”

Section: Introductionmentioning

confidence: 99%

MiR-224 Executes a Tumor Accelerative Role during Hepatocellular Carcinoma Malignancy by Targeting Cytoplasmic Polyadenylation Element-Binding Protein 3

Miao¹,

Liu

Huang

et al. 2020

Pharmacology

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The purpose of our study was to probe the mechanism of how miR-224/cytoplasmic polyadenylation element-binding protein 3 (CPEB3) axis is concerned with hepatocellular carcinoma (HCC). Methods: The expressions and prognostic values of miR-224 and CPEB3 in HCC patients were analyzed based on the data acquired from the TCGA and GEO databases. qRT-PCR was conducted to test the mRNA expression levels of miR-224 and CPEB3. The expression level of miR-224 in SMMC-7721/HuH-7 cells was up-/downregulated by miR-224 mimic/inhibitor to explore its influence on HCC cell proliferation and motility by utilizing CCK8 and transwell assays, respectively. Luciferase activity assay was applied for verifying the target of miR-224. The relationship between miR-224 and CPEB3 was analyzed utilizing Pearson's correlation coefficient. The protein level of CPEB3 was tested by Western blotting. Rescue assay was performed to determine whether CPEB3 involved in the process of HCC cell phenotype changes caused by miR-224 alteration. Results: MiR-224 was highly expressed and CPEB3 was lowly expressed in HCC tissues. Besides, the high expression of miR-224 and low expression of CPEB3 were correlated with worse prognosis in HCC patients. Up-/downregulation of miR-224 accelerated/restrained SMMC-7721/ HuH-7 cell proliferation and motility. CPEB3 was predicted and proofed as a target gene of miR-224. We discovered that CPEB3 was negatively modulated by miR-224. We also found a sharply negative correlation between CPEB3 and miR-224. Using rescue assay, we showed that overexpression of CPEB3 suppressed the proliferation and motility of SMMC-7721 cells with overexpressed miR-224, while knockdown of CPEB3 facilitated the proliferation and motility of HuH-7 cells with downregulated miR-224. Conclusion: Our data provided evidences that miR-224 is implicated in HCC cell proliferation and motility via targeting CPEB3. The relationship between miR-224 and CPEB3 might be a novel finding, and miR-224/CPEB3 axis might be markers for providing therapeutic and prognostic information in HCC.

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“…We reviewed the literature to evaluate the viability of proposed miRNA inputs. miR-221, miR-93 and miR-224 are described as up-regulated (Liu et al, 2016;Ji et al, 2017;Hung et al, 2018) and miR-99a is described as down-regulated in HCC cells (Zhang et al, 2014). Although miR-221 is described as highly expressed in HCC tissues, the miRNA appears nonnegated in 2 rules and once negated together with non-negated miR-93 (miR-93 AND NOT miR-221).…”

Section: Hcc Classifier Evaluationmentioning

confidence: 99%

A framework for designing miRNA-based distributed cell classifier circuits

Nowicka

Siebert

2020

Preprint

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MotivationCell classifiers are synthetic bio-devices performing type-specific in vivo classification. The circuits identify a cell state based on its molecular fingerprint. In particular, the classifiers may be designed to recognize cancerous cells and trigger their apoptosis, shaping a novel therapy for cancer patients. Recently, we introduced a new theoretical design of such devices employing distributed classifiers. Here, a group of single-circuit classifiers decides collectively according to a pre-defined threshold function whether a cell is cancerous. The multi-circuit architecture has shown the potential to predict the cell condition with high accuracy. However, lack of far-reaching machinery to design and evaluate distributed cell classifiers, in particular, assessing their robustness to noise and novel information, makes their application limited.ResultsIn this study, we present a comprehensive framework for designing and evaluating miRNA-based distributed cell classifiers comprising data simulation, pre-processing, and an extensive testing scheme. We develop optimization criteria that allow increasing the accuracy and robustness of classifiers to noise and novel information as shown in simulated and real-world data studies. The evaluation performed on cancer data demonstrates that distributed classifiers outperform single-circuit designs in terms of prediction accuracy. Our classifiers include relevant miRNAs previously described in the literature, as well as more complex regulation patterns included in the data.AvailabilityThe code and data are available at: https://github.com/MelaniaNowicka/RAccoon.Contactm.nowicka@fu-berlin.de

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MicroRNA-224 down-regulates Glycine N-methyltransferase gene expression in Hepatocellular Carcinoma

Cited by 22 publications

References 61 publications

Diagnostic Performance of microRNA-122 and microRNA-224 in Hepatitis C Virus-Induced Hepatocellular Carcinoma (HCC)

Diagnostic Performance of microRNA-122 and microRNA-224 in Hepatitis C Virus-Induced Hepatocellular Carcinoma (HCC)

MiR-224 Executes a Tumor Accelerative Role during Hepatocellular Carcinoma Malignancy by Targeting Cytoplasmic Polyadenylation Element-Binding Protein 3

A framework for designing miRNA-based distributed cell classifier circuits

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