Integrin α9 gene promoter is hypermethylated and downregulated in nasopharyngeal carcinoma

Nawaz, Imran; Hu, Li–Fu; Du, Ziwei; Moumad, Khalid; Ignatyev, Ilya; Pavlova, Tatiana V.; Kashuba, Vladimir I.; Almgren, Malin; Zabarovsky, Eugene R.; Ernberg, Ingemar

doi:10.18632/oncotarget.5154

Cited by 19 publications

(9 citation statements)

References 66 publications

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“…DNA methylation, which is a common mechanism in epigenetic alterations, may be correlated with NPC ( Jiang et al, 2015 , Nawaz et al, 2015a ). Promoter methylation of tumor suppressor genes (TSGs), such as calcium channel voltage-dependent alpha 2/delta subunit 3 ( CACNA2D3 ) and cadherin 4 ( CDH4 ), may play a crucial role in NPC development and progression ( Wong et al, 2013 , Du et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Capacity of RASSF1A Promoter Methylation as a Biomarker in Tissue, Brushing, and Blood Samples of Nasopharyngeal Carcinoma

et al. 2017

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Methylation of the RAS association domain family protein 1A (RASSF1A) promoter has been observed in nasopharyngeal carcinoma (NPC). This study investigated the correlation of RASSF1A promoter methylation with clinicopathological features and its utility as a diagnostic biomarker in NPC. A total of 926 patients with NPC and 495 non-tumor controls were analyzed in this study. RASSF1A promoter methylation was notably higher in NPC compared with non-tumor tissue, brushing and blood samples. RASSF1A promoter methylation was associated with clinical stage, lymph node status, distant metastasis, and T classification of patients with NPC, although it was not linked to age and sex. The pooled sensitivity, specificity, and AUC (area under the curve) of RASSF1A promoter methylation were determined in NPC samples vs. non-tumor samples (tissue: sensitivity = 0.72, specificity = 0.99, AUC = 0.98; brushing: sensitivity = 0.56, specificity = 1.00, AUC = 0.94; blood: sensitivity = 0.11, specificity = 0.98, AUC = 0.97). Our findings show that RASSF1A promoter methylation may be correlated with the development, progression and metastasis of NPC. RASSF1A promoter methylation is a promising noninvasive biomarker for the diagnosis of NPC from tissue and brushing samples.

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Section: Introductionmentioning

confidence: 99%

Diagnostic Capacity of RASSF1A Promoter Methylation as a Biomarker in Tissue, Brushing, and Blood Samples of Nasopharyngeal Carcinoma

et al. 2017

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“…A previous study reported that upregulation of ITGA9 in response to a decrease in miR-125b levels in metastatic melanoma is responsible for melanoma tumor cell migration and invasion (63). In addition, ITGA9 is associated with other types of cancer, including nasopharyngeal carcinoma (64), breast cancer (65) and colorectal cancer (66). PIK3R1 is a target of miR-29b and miR-221, which may enhance chemosensitivity to gemcitabine in HuH28 human CCA cells (67).…”

Section: Discussionmentioning

confidence: 99%

Upregulation of miR‑132‑3p in cholangiocarcinoma tissues: A study based on RT‑qPCR, The Cancer Genome Atlas miRNA sequencing, Gene Expression Omnibus microarray data and bioinformatics analyses

Xia

Liu

et al. 2019

Mol Med Report

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MicroRNAs (miRNAs/miRs) have been reported to be closely associated with numerous human diseases, including cholangiocarcinoma (CCA). However, the number of miRNAs known to be involved in CCA is limited, and the association between miR-132-3p and CCA remains unknown. In the present study, the clinical role of miR-132-3p and its potential signaling pathways were investigated by multiple approaches. Reverse transcription-quantitative PCR (RT-qPCR), CCA-associated Gene Expression Omnibus (GEO), ArrayExpress and Sequence Read Archive (SRA) miRNA-microarray or miRNA-sequencing data were screened, and meta-analyses were conducted, in order to calculate the receiver operating characteristic (ROC) curve and standardized mean difference (SMD). The predicted target genes of miR-132-3p were obtained from 12 online databases and were combined with the downregulated differentially expressed genes identified in the RNA-sequencing data of CCA. Gene Ontology annotation and pathway analysis were performed in WebGestalt. Protein-protein interaction analyses were conducted in STRING. The Cancer Genome Atlas (TCGA) mRNA expression profiles were used to validate the expression levels of hub genes at the mRNA level. The Human Protein Atlas was used to identify the protein expression levels of hub genes in CCA tissues and non-tumor biliary epithelium. The meta-analyses comprised 10 groups of RT-qPCR data, eight GEO microarray datasets and one TCGA miRNA-sequencing dataset. The SMD of miR-132-3p in CCA was 0.75 (95% CI: 0.25, 1.24), which indicated that miR-132-3p was overexpressed in CCA tissues. This finding was supported by a summary ROC value of 0.80 (95% CI: 0.76, 0.83). The pooled sensitivity and specificity were 0.81 (95% CI: 0.59, 0.93) and 0.71 (95% CI: 0.58, 0.81), respectively. The relative expression level of miR-132-3p in the early stage of CCA (stages I–II) was 6.8754±0.5279, which was markedly lower than that in the advanced stage (stages III–IVB), 7.3034±0.3267 (P=0.003). Consistently, the miR-132-3p level in low-grade CCA (grades G1-G2) was 6.7581±0.5297, whereas it was 7.1191±0.4651 in patients with high-grade CCA (grades G3-G4) (P=0.037). Furthermore, 555 potential target genes of miR-132-3p in CCA were mainly enriched in the ‘Focal Adhesion-PI3K-Akt-mTOR-signaling pathway’. In conclusion, upregulation of miR-132-3p may serve a pivotal role in the tumorigenesis and progression of CCA by targeting different pathways. Further in vitro and in vivo studies are required to support the current findings.

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“…Besides, ITGA9 mRNA level was significantly downregulated in bladder cancer tissues compared with the corresponding adjacent to the tumor tissues [ 33 ]. Nawaz et al have reported that ITGA9 promoter was downregulated by aberrant hypermethylation in promoter and probably facilitated the process of nasopharyngeal carcinoma [ 34 ]. Nevertheless, our data revealed that ITGA9 not only restrains tumor growth but also suppresses tumor metastasis to prevent HCC progression.…”

Section: Discussionmentioning

confidence: 99%

Integrin α9 Suppresses Hepatocellular Carcinoma Metastasis by Rho GTPase Signaling

Zhang

Xing²,

Cai

et al. 2018

Journal of Immunology Research

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Integrin subunit alpha 9 (ITGA9) mediates cell-cell and cell-matrix adhesion, cell migration, and invasion through binding different kinds of extracellular matrix (ECM) components. However, its potential role and underlying molecular mechanisms remain unclear in hepatocellular carcinoma (HCC). Here, we found that ITGA9 expression was obviously decreased in patients with HCC, which was negatively correlated with HCC growth and metastasis. ITGA9 overexpression significantly inhibited cell proliferation and migration in vitro as well as tumor growth and metastasis in vivo. Our data demonstrated that the inhibitory effect of ITGA9 on HCC cell motility was associated with reduced phosphorylation of focal adhesion kinase (FAK) and c-Src tyrosine kinase (Src), disrupted focal adhesion reorganization, and decreased Rac1 and RhoA activity. Our data suggest ITGA9, as a suppressor of HCC, prevents tumor cell migration and invasiveness through FAK/Src-Rac1/RhoA signaling.

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Integrin α9 gene promoter is hypermethylated and downregulated in nasopharyngeal carcinoma

Cited by 19 publications

References 66 publications

Diagnostic Capacity of RASSF1A Promoter Methylation as a Biomarker in Tissue, Brushing, and Blood Samples of Nasopharyngeal Carcinoma

Diagnostic Capacity of RASSF1A Promoter Methylation as a Biomarker in Tissue, Brushing, and Blood Samples of Nasopharyngeal Carcinoma

Upregulation of miR‑132‑3p in cholangiocarcinoma tissues: A study based on RT‑qPCR, The Cancer Genome Atlas miRNA sequencing, Gene Expression Omnibus microarray data and bioinformatics analyses

Integrin α9 Suppresses Hepatocellular Carcinoma Metastasis by Rho GTPase Signaling

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