Dataset Information

MiR-302b inhibits tumorigenesis by targeting EphA2 via Wnt/ ?-catenin/EMT signaling cascade in gastric cancer.

ABSTRACT: BACKGROUND:EphA2 is a crucial oncogene in gastric cancer (GC) development and metastasis, this study aims to identify microRNAs that target it and serve as key regulators of gastric carcinogenesis. METHODS:We identified several potential microRNAs targeting EphA2 by bioinformatics websites and then analyzed the role of miR-302b in modulating EphA2 in vitro and in vivo of GC, and it's mechanism. RESULTS:Our analysis identified miR-302b, a novel regulator of EphA2, as one of the most significantly downregulated microRNA (miRNA) in GC tissues. Overexpression of miR-302b impaired GC cell migratory and invasive properties robustly and suppressed cell proliferation by arresting cells at G0-G1 phase in vitro. miR-302b exhibited anti-tumor activity by reversing EphA2 regulation, which relayed a signaling transduction cascade that attenuated the functions of N-cadherin, ?-catenin, and Snail (markers of Wnt/?-catenin and epithelial-mesenchymal transition, EMT). This modulation of EphA2 also had distinct effects on cell proliferation and migration in GC in vivo. CONCLUSIONS:miR-302b serves as a critical suppressor of GC cell tumorigenesis and metastasis by targeting the EphA2/Wnt/?-catenin/EMT pathway.

SUBMITTER: Huang J

PROVIDER: S-EPMC5741943 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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miR-302b inhibits tumorigenesis by targeting EphA2 via Wnt/ β-catenin/EMT signaling cascade in gastric cancer.

Huang Jin J He Yijing Y Mcleod Howard L HL Xie Yanchun Y Xiao Desheng D Hu Huabin H Chen Pan P Shen Liangfang L Zeng Shan S Yin Xianli X Ge Jie J Li Li L Tang Lanhua L Ma Jian J Chen Zihua Z

BMC cancer 20171222 1

<h4>Background</h4>EphA2 is a crucial oncogene in gastric cancer (GC) development and metastasis, this study aims to identify microRNAs that target it and serve as key regulators of gastric carcinogenesis.<h4>Methods</h4>We identified several potential microRNAs targeting EphA2 by bioinformatics websites and then analyzed the role of miR-302b in modulating EphA2 in vitro and in vivo of GC, and it's mechanism.<h4>Results</h4>Our analysis identified miR-302b, a novel regulator of EphA2, as one of ...[more]

PMID: 29273006

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Project description:BACKGROUND:Gastric cancer (GC) is a common malignancy and frequent cause of cancer-related death. Long non-coding RNAs (lncRNAs) have emerged as important regulators and tissue-specific biomarkers of multiple cancers, including GC. Recent evidence has indicated that the novel lncRNA LINC01133 plays an important role in cancer progression and metastasis. However, its function and molecular mechanism in GC remain largely unknown. METHODS:LINC01133 expression was detected in 200 GC and matched non-cancerous tissues by quantitative reverse transcription PCR. Gain- and loss-of-function experiments were conducted to investigate the biological functions of LINC01133 both in vitro and in vivo. Insights into the underlying mechanisms of competitive endogenous RNAs (ceRNAs) were determined by bioinformatics analysis, dual-luciferase reporter assays, quantitative PCR arrays, TOPFlash/FOPFlash reporter assay, luciferase assay, and rescue experiments. RESULTS:LINC01133 was downregulated in GC tissues and cell lines, and its low expression positively correlated with GC progression and metastasis. Functionally, LINC01133 depletion promoted cell proliferation, migration, and the epithelial-mesenchymal transition (EMT) in GC cells, whereas LINC01133 overexpression resulted in the opposite effects both in vitro and in vivo. Bioinformatics analysis and luciferase assays revealed that miR-106a-3p was a direct target of LINC01133, which functioned as a ceRNA in regulating GC metastasis. Mechanistic analysis demonstrated that miR-106a-3p specifically targeted the adenomatous polyposis coli (APC) gene, and LINC01133/miR-106a-3p suppressed the EMT and metastasis by inactivating the Wnt/?-catenin pathway in an APC-dependent manner. CONCLUSIONS:Our findings suggest that reduced expression of LINC01133 is associated with aggressive tumor phenotypes and poor patient outcomes in GC. LINC01133 inhibits GC progression and metastasis by acting as a ceRNA for miR-106a-3p to regulate APC expression and the Wnt/?-catenin pathway, suggesting that LINC01133 may serve as a potential prognostic biomarker and anti-metastatic therapeutic target for GC.

Dataset Information

MiR-302b inhibits tumorigenesis by targeting EphA2 via Wnt/ ?-catenin/EMT signaling cascade in gastric cancer.

Publications

miR-302b inhibits tumorigenesis by targeting EphA2 via Wnt/ β-catenin/EMT signaling cascade in gastric cancer.

Similar Datasets

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