Direct repression of the oncogene CDK4 by the tumor suppressor miR-486-5p in non-small cell lung cancer

Shao, Yang; Shen, Yuqing; Li, Yanli; Liang, Changhong; Zhang, Bing-Jie; Lu, Shengdi; Wang, Ping; Sun, Qiangling; Jin, Youxin

doi:10.18632/oncotarget.8514

Cited by 63 publications

(48 citation statements)

References 47 publications

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“…1A). Although miR-486-5p down-regulation and its effects in promoting lung carcinogenesis have been previously reported [3,8–10], the mechanism of repression is unknown. MicroRNAome analysis of NSCLC cell lines treated with vehicle or DAC as described [33] showed that DAC treatment increased miR-486-5p expression in 5/10 cell lines with lowest expression by 2 to 8-fold (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, abnormal repression of this miR in cancer provides a growth advantage by enhancing the tumor-promoting properties of its targets. Among miR-486-5p target oncogenes that get activated following its downregulation in lung cancer include: CDK4, which promote cell cycle progression [3], ARHGAP5, which regulates cellular adhesion, motility, and polarity to promote cell migration and invasion [10], the growth promoting IGF signaling genes IGF1, IGF1R, and PIK3R1 [9], and the proto-oncogene serine/threonine kinase PIM-1 [8]. The tumor-suppressor role of miR-486-5p is also demonstrated in other cancers where it targets PIM-1 in breast cancer [43], SNAI1 in prostate cancer [44], and CLDN10, CITRON, and PIK3R1 in HCC [45,46] [45].…”

Section: Discussionmentioning

confidence: 99%

“…Some miRs target key oncogenic or tumor-suppressor genes and thereby play a critical role in inhibiting or promoting carcinogenesis, respectively [2]. MiR-486-5p is a tumor-suppressor miR that is often down-regulated across multiple malignancies including lung [3,4], gastric [5], pancreatic [6], and other [7] cancers. In vitro and laboratory animal based gain- or loss-of-function studies on miR-486-5p have confirmed its role in suppressing the growth of lung cancer [8–10].…”

Section: Introductionmentioning

confidence: 99%

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ANK1 Methylation regulates expression of MicroRNA-486-5p and discriminates lung tumors by histology and smoking status

et al. 2017

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The intragenic tumor-suppressor microRNA miR-486-5p is often down-regulated in non-small cell lung cancer (NSCLC) but the mechanism is unclear. This study investigated epigenetic co-regulation of miR-486-5p and its host gene ANK1. MiR-486-5p expression in lung tumors and cell lines was significantly reduced compared to normal lung (p<0.001) and is strongly correlated with ANK1 expression. In vitro, siRNA-mediated ANK1 knockdown in NSCLC cells also reduced miR-486-5p while the DNA methylation inhibitor 5-aza-2′-deoxycytidine induced expression of both. ANK1 promoter CpG island was unmethylated in normal lung but methylated in 45% (118/262) lung tumors and 55% (17/31) NSCLC cell lines. After adjustment for tumor histology and smoking, methylation was significantly more prevalent in adenocarcinoma (101/200, 51%) compared to squamous cell carcinoma (17/62, 27%), p<0.001; HR=3.513 (CI: 1.818–6.788); and in smokers (73/128, 57%) than never-smokers (28/72, 39%), p=0.014; HR=2.086 (CI: 1.157–3.759). These results were independently validated using quantitative methylation data for 809 NSCLC cases from The Cancer Genome Atlas project. Together, our data indicate that aberrant ANK1 methylation is highly prevalent in lung cancer, discriminate tumors by histology and patients’ smoking history, and contributes to miR-486-5p repression.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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ANK1 Methylation regulates expression of MicroRNA-486-5p and discriminates lung tumors by histology and smoking status

et al. 2017

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“…Studies have reported that aberrant miR-486-5p expression could affect the occurrence and progression of many diseases [26,27]. Notably, the effect of miR-486-5p is controversial because it was found to serve as a suppressor or oncogene in studies [28,29]. In addition, we saw that miR-486-5p's function had not been explored in COPD.…”

Section: Discussionmentioning

confidence: 91%

miRNA-486-5p Promotes COPD Progression by Targeting HAT1 to Regulate the TLR4-Triggered Inflammatory Response of Alveolar Macrophages

Zhang

Kong

et al. 2020

Preprint

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Background: The aim of this study is to investigate the key regulatory miRNA-486-5p and underlying molecular mechanisms in chronic obstructive pulmonary disease (COPD) progression.Methods: Aberrant miRNA expression in smokers compared to non-smokers and COPD compared to normal was analyzed using microarray datasets and reverse-transcriptase quantitative polymerase chain reaction (qPCR). ELISA assay was used to determine the secretion of inflammatory cytokines in cell supernatants. Inflammatory cytokine expression, including HAT1, TLR4, and miR-486-5p, was determined using qPCR or western blotting. Luciferase reporter assays and fluorescence in situ hybridization were used to confirm the target regulation between miR-486-6p and HAT1. Results: Our results showed that miR-486-5p was significantly up-regulated in the COPD and smoker groups compared to the control group based on bioinformatics analysis and qPCR validation of alveolar macrophages and peripheral monocytes. miR-218-5p expression significantly correlated with IL-6, IL-8, TNF-α, and IFN-γ expression. Luciferase reporter assays confirmed that miR-486-5p directly targets HAT1, and cellular localization showed that miR-486-5p and HAT1 were highly expressed in the cytoplasm. miR-486-5p overexpression led to significant TLR4 up-regulation and significant HAT1 down-regulation. Inversely, miR-486-5p inhibition led to significant TLR4 down-regulation and significant HAT1 up-regulation. HAT1 knockdown using siRNA significantly increased TLR4, IL-6, IL-8, TNF-α, and IFN-γ expression. Conclusions: miR-486-5p was differentially expressed in alveolar macrophages of COPD patients. miR-486-5p overexpression might increase the TLR4-triggered inflammatory response in COPD patients by targeting HAT1.

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“…We found that mir-486 had tumor suppressing effect in LUAD, and many previous studies support this conclusion. Yu et al found that miR-486 inhibits cell proliferation and invasion through repressing GAB2 in LUAD [40], and miR-486played an anti-tumor function by targeting CDK4 in LUAD [41].…”

Section: Discussionmentioning

confidence: 99%

Identification of Stage-associated MicroRNAs in Lung Adenocarcinoma Based on Microarray Data

Wang

Gao

et al. 2020

Preprint

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Background: Lung adenocarcinoma (LUAD) is the most aggressive and most frequently seen histological variant of lung cancers, comprising nearly 45% of the overall cases of lung carcinoma and its incidence has been increased significantly worldwide in the last several decades. However, there was limited available evidence with respect to the signalling pathways and miRNAs related to the LUAD.Methods: To identify the differentially-expressed miRNAs (DE-miRNAs) in different stages of LUAD, we performed a microarray on 514 LUAD and 54 normal tissues. At the mean time, the potentially targeted genes as well as the highly-enriched signaling pathways and the relevant protein–protein interaction (PPI) network were analyzed and constructed by using a series of bioinformatic methods. Moreover, the identified DE-miRNAs in different stages of the LUAD were verified by using the TCGA dataset.Results : Overall 41 down-regulated -and 82 up-regulated DE-miRNAs were identified, of which 1,716 potential targeted genes were selected. Moreover, the enriched pathways of the above genes were screened by using the GO term and KEGG pathway analyses, including the AMPK signalling pathway, FoxO signalling pathway, MAPK signalling pathway, PI3K-Akt signalling pathway and hippo signalling pathway.Conclusions: Our study could provide additional understanding of the underlying molecular events and increase the precision of prognostic prediction.

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Direct repression of the oncogene CDK4 by the tumor suppressor miR-486-5p in non-small cell lung cancer

Cited by 63 publications

References 47 publications

ANK1 Methylation regulates expression of MicroRNA-486-5p and discriminates lung tumors by histology and smoking status

ANK1 Methylation regulates expression of MicroRNA-486-5p and discriminates lung tumors by histology and smoking status

miRNA-486-5p Promotes COPD Progression by Targeting HAT1 to Regulate the TLR4-Triggered Inflammatory Response of Alveolar Macrophages

Identification of Stage-associated MicroRNAs in Lung Adenocarcinoma Based on Microarray Data

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