MicroRNA-126 functions as a tumor suppressor in colorectal cancer cells by targeting CXCR4 via the AKT and ERK1/2 signaling pathways

Liu, Yaling; Zhou, Yu; Xiao, Feng; An, Ping; Quan, Xiaojing; Wang, Hao; Ye, Shicai; Yu, Caiyuan; Yang, He; Luo, Haitao

doi:10.3892/ijo.2013.2168

Cited by 75 publications

(53 citation statements)

References 35 publications

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“…In the present study, we found that miR-126 was downregulated in ECs and that its downregulation was induced by promoter hypermethylation of its host gene. Dysregulation of miR-126 has also been observed in other tumors, such as colon cancer (32) and lung cancer (33), but little is known about its function in ESCC. This is the first report to show that miR-126 is downregulated and acts as a new tumor suppressor in ESCC.…”

Section: Discussionmentioning

confidence: 99%

DNMT1–MicroRNA126 Epigenetic Circuit Contributes to Esophageal Squamous Cell Carcinoma Growth via ADAM9–EGFR–AKT Signaling

Liu

Jiang

et al. 2015

Clinical Cancer Research

100

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Purpose: MicroRNAs (miRNA) are involved in and are controlled by epigenetic regulation, and thereby form a reciprocal regulatory circuit. Using next-generation sequencing (NGS)-based miRNA profiling, this study aimed to discover esophageal squamous cell carcinoma (ESCC)-specific miRNAs and miRNArelated epigenetic modulations.Experimental Design: NGS-based miRNA profiles were generated for four pairs of ESCC tissues and adjacent normal tissues. In situ hybridization was used to assess miRNA expression and its correlation with prognosis. miRNA-related DNA methylations were identified using bisulfite genomic sequencing, and the role of DNA methyltransferase 1 (DNMT1) was investigated using RNA interference. miRNA targets were screened by mRNA sequencing, and functional validation was performed in vitro and in vivo.Results: NGS-based miRNA profiling identified 78 differentially expressed miRNAs in ESCC. Among them, microRNA126-3p (miR-126) was significantly downregulated, and its downregulation correlated with poor ESCC prognosis. Downregulation of miR-126 was due to promoter hypermethylation of its host gene, Egfl7. DNMT1 was aberrantly upregulated in ESCC and responsible for the hypermethylation of Egfl7. Intriguingly, DNMT1 was suppressed by overexpression of miR-126, indicating the existence of a regulatory feedback circuit. ADAM9 was identified as a key target of miR-126. Ectopic expression of miR-126 or silencing of ADAM9 reduced ESCC cell proliferation and migration by inhibiting epidermal growth factor receptor-AKT signaling.Conclusions: Our results indicate that miR-126 is a potential prognostic indicator for ESCC and suggest that a novel "DNMT1-miR-126 epigenetic circuit" is involved in ESCC progression. Consequently, miR-126-based epigenetic modulations may provide a basic rationale for new approaches to antitumor therapeutics.

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Section: Discussionmentioning

confidence: 99%

DNMT1–MicroRNA126 Epigenetic Circuit Contributes to Esophageal Squamous Cell Carcinoma Growth via ADAM9–EGFR–AKT Signaling

Liu

Jiang

et al. 2015

Clinical Cancer Research

100

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“…Knockout of miR-126-3p can cause a loss in blood vessel integrity and result in hemorrhage during embryonic development in zebrafish, showing that miR-126-3p controls blood vessel integrity and angiogenesis [15]. Many studies have suggested that miR-126-3p plays a part as either an anti-oncogene or an oncogene in different cancers [16, 17]. miR-126-3p also acts as a tumor suppressor via the downregulation of intron 7 of epidermal growth factor-like domain 7 (EGFL7) and it may be a promising candidate for therapeutic strategies in oral squamous cell carcinoma [18].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-126-3p suppresses cell proliferation by targeting PIK3R2 in Kaposi's sarcoma cells

Zhao

Kang

et al. 2016

Oncotarget

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Kaposi's sarcoma is a highly vascular tumor of lymphatic endothelial origin. Many deregulated miRNAs, including miR-126-3p, have been identified in Kaposi's sarcoma tissues. miR-126-3p is the most highly endothelial-specific miRNA that regulates vascular integrity and angiogenesis. In this study, we aimed to determine the effect of miR-126-3p on Kaposi's sarcoma cells through transfection of a miRNA mimic and inhibitor. Moreover, we searched the target gene (PIK3R2) of miR-126-3p using bioinformatics software and further verified PIK3R2 using luciferase reporter assays, Real-time quantitative PCR (qRT-PCR) and western blot. The results demonstrated that miR-126-3p inhibited cell proliferation, arrested cell cycle progression, induced cell apoptosis, and inhibited cell invasion of SLK cells. The bioinformatics analysis and luciferase reporter assay revealed that PIK3R2 mRNA is a direct target of miR-126-3p. Moreover, the level of expression of the PIK3R2 gene was downregulated in SLK cells transfected with miR-126-3p siRNAs. Therefore, our data demonstrated that miR-126-3p is a tumor suppressor miRNA that acts by targeting PIK3R2 in Kaposi's sarcoma cells. These findings contribute to our understanding of the molecular mechanisms underlying Kaposi's sarcoma.

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“…Discussion dysregulated miRNA expression is responsible for the initiation and progression of several types of human cancers. Recent evidence has demonstrated that aberrant miRNA expression affects cell proliferation, invasion, apoptosis, and chemosensitivity (17)(18)(19). Among these miRNAs, miR-203 remains an important subject of investigation since its role as a tumor suppressor gene or oncogene remains largely undetermined.…”

Section: Overexpressed Mir-203 Induces Apoptosis and Decreases Cell Imentioning

confidence: 99%

MicroRNA-203 induces apoptosis by upregulating Puma expression in colon and lung cancer cells

Funamizu

Lacy

Kamada

et al. 2015

International Journal of Oncology

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Abstract. The present study investigated the relationship between and the p53 upregulated modulator of apoptosis (Puma) in colon (HCT116) and lung cancer (A549) cells. Colon and lung cancer cell lines were selected for this study since a relationship between p53/miR-203 and p53/Puma has been established in both cancers. In the present study, adriamycin and nutlin-3 were used to activate p53, which induced both miR-203 and Puma expression in HCT116 cells. In contrast, HCT 116 cells with downregulated p53 showed decreased miR-203 and Puma expression. Importantly, we found that overexpressed miR-203 in HCT116 cells resulted in significantly increased Puma expression (P<0.05). Based on these findings, we hypothesized that another limb of the p53/Puma axis depends on miR-203 expression. To further validate this relationship, we used lung cancer cells (A549) and found that activated p53 increased both miR-203 and Puma expression. In addition, we found that Puma expression remained elevated in cells with overexpressed miR-203 in the presence of p53 downregulation. Cumulatively, our data purport that p53 not only increased Puma expression directly, but that it may also do so through miR-203. Additionally, functional studies revealed that miR-203 overexpression induced apoptosis and inhibited cell invasiveness.

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MicroRNA-126 functions as a tumor suppressor in colorectal cancer cells by targeting CXCR4 via the AKT and ERK1/2 signaling pathways

Cited by 75 publications

References 35 publications

DNMT1–MicroRNA126 Epigenetic Circuit Contributes to Esophageal Squamous Cell Carcinoma Growth via ADAM9–EGFR–AKT Signaling

DNMT1–MicroRNA126 Epigenetic Circuit Contributes to Esophageal Squamous Cell Carcinoma Growth via ADAM9–EGFR–AKT Signaling

MicroRNA-126-3p suppresses cell proliferation by targeting PIK3R2 in Kaposi's sarcoma cells

MicroRNA-203 induces apoptosis by upregulating Puma expression in colon and lung cancer cells

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