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MicroRNA-148a-3p inhibits cancer progression and is a novel screening biomarker for gastric cancer.

ABSTRACT: PURPOSE:Dysregulation of miR-148a-3p in gastric cancer was reported. However, the diagnostic potential and biological function of miR-148a-3p in gastric cancer progression is not fully studied. METHODS:Bioinformatics analysis and RT-qPCR assay were performed to analyze the expression of miR-148a-3p in gastric cancer tissues and plasma of gastric cancer patients. Receiver operating characteristic curve analysis was performed to analyze the diagnostic value of miR-148a-3p. In vitro proliferation, apoptosis, migration, invasion, sphere formation assay and Western blotting assay were performed to evaluate the biological function of miR-148a-3p in gastric cancer progression. RESULTS:miR-148a-3p was significantly down-regulated in both gastric cancer patients' tissue and plasma samples. Plasma miR-148a-3p showed promising efficacy for gastric cancer diagnosis. Overexpression of miR-148a-3p could inhibit the proliferative phenotype, metastatic phenotype, and cancer stem-like properties of gastric cancer cells. CONCLUSIONS:miR-148a-3p inhibits cancer progression and is a novel diagnostic biomarker for gastric cancer.

SUBMITTER: Bao C

PROVIDER: S-EPMC7595888 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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MicroRNA-148a-3p inhibits cancer progression and is a novel screening biomarker for gastric cancer.

Bao Chenhui C Guo Lin L

Journal of clinical laboratory analysis 20200812 10

<h4>Purpose</h4>Dysregulation of miR-148a-3p in gastric cancer was reported. However, the diagnostic potential and biological function of miR-148a-3p in gastric cancer progression is not fully studied.<h4>Methods</h4>Bioinformatics analysis and RT-qPCR assay were performed to analyze the expression of miR-148a-3p in gastric cancer tissues and plasma of gastric cancer patients. Receiver operating characteristic curve analysis was performed to analyze the diagnostic value of miR-148a-3p. In vitro ...[more]

PMID: 32785967

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Project description:BackgroundHepatocellular carcinoma (HCC) is one of the most prevalent common cancer worldwide with high mortality. Transforming growth factor-β (TGF-β) signaling pathway was reported dysregulated during liver cancer formation and progression. As a key component of TGF-β signaling, the role of SMAD2 and its regulatory mechanisms in HCC remain unclear.MethodsSMAD2 expression in paired HCC specimens were determined by western blot and immunohistochemistry (IHC). quantitative real-time PCR (qRT-PCR) was used to measure mRNA and microRNA (miRNA) expression level. Cell migration, invasion and proliferation ability were evaluated by transwell, CCK8 and EdU assay. In silico websites were used to manifest overall survival rates of HCC patients or to predict miRNAs targeting SMAD2. Dual luciferase reporter assay and anti-Ago2 immunoprecipitation assay were performed to confirm the binding between SMAD2 mRNA and miRNA-148a-3p (miR-148a). Tumorigenesis and lung metastasis mouse model were used to explore the role of miR-148a in vivo. In situ hybridization (ISH) was conducted to determine the expression of miR-148a in liver tissues.ResultsIn this study, we found that SMAD2 was highly expressed in HCC and elevated SMAD2 expression predicted shorter overall survival (OS) time for HCC patients. SMAD2 promoted mobility and proliferation of HCC cells in vitro. We further revealed that the expression of miR-148a was negatively correlated with SMAD2 and found that miR-148a repressed SMAD2 expression by downregulating its mRNA through binding with Argonaute 2 (Ago2) in HCC. Transwell, CCK8 and animal experiments exhibited miR-148a inhibited metastasis and proliferation of HCC in vitro and in vivo. Moreover, the phenotype changes caused by miR-148a manipulation were recovered by rescuing SMAD2 expression in HCC cells. ISH assay indicated miR-148a was downregulated in HCC and low expression of miR-148a associated with more aggressive clinic features and poor prognosis.ConclusionmiR-148a was identified as a repressor of HCC progression by downregulating SMAD2 in an Ago2 dependent manner.

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MicroRNA-148a-3p inhibits cancer progression and is a novel screening biomarker for gastric cancer.

Publications

MicroRNA-148a-3p inhibits cancer progression and is a novel screening biomarker for gastric cancer.

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