Dataset Information

CADM2, as a new target of miR-10b, promotes tumor metastasis through FAK/AKT pathway in hepatocellular carcinoma.

ABSTRACT: BACKGROUND:Cell adhesion molecules (CADMs) comprise of a protein family whose functions include maintenance of cell polarity and tumor suppression. Hypo-expression of CADM2 gene expression has been observed in several cancers including hepatocellular carcinoma (HCC). However, the role and mechanisms of CADM2 in HCC remain unclear. METHODS:The expression of CADM2 and miRNA-10b (miR-10b) in HCC tissues and cell lines were detected using real-time PCR and Western blotting. Immunofluorescence was used to detect Epithelial-mesenchymal transition (EMT) progression in HCC cell lines. Dual-luciferase reporter assay was used to determine miR-10b binding to CADM2 3'UTR. Wound healing assay and Transwell assay were performed to examine the migration and invasion of HCC cells. RESULTS:We report the effect of CADM2 as a tumor suppressor in HCC. Firstly, we confirmed that CADM2 expression was significantly down regulated in HCC tissues compared to normal tissues according to TCGA data analysis and fresh HCC sample detection. Secondly, overexpression of CADM2 could inhibit EMT process, migratory and invasion ability of HCC cells. Furthermore, the results indicated that CADM2 is a direct target of miR-10b in HCC cells and miR-10b/CADM2 modulates EMT process and migration ability via focal adhesion kinase (FAK) /AKT signaling pathway in HCC. CONCLUSIONS:Our study demonstrates that miR-10b-CADM2-FAK/AKT axis plays an important role in HCC metastasis, which might be a novel potential therapeutic option for HCC treatment.

SUBMITTER: Li D

PROVIDER: S-EPMC5836378 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CADM2, as a new target of miR-10b, promotes tumor metastasis through FAK/AKT pathway in hepatocellular carcinoma.

Li Dongliang D Zhang Yongjian Y Zhang He H Zhan Chao C Li Xin X Ba Tu T Qiu Zini Z E Fang F Lv Guixiang G Zou Chendan C Wang Chuxuan C Si Lining L Zou Chaoxia C Li Qiang Q Gao Xu X

Journal of experimental & clinical cancer research : CR 20180305 1

<h4>Background</h4>Cell adhesion molecules (CADMs) comprise of a protein family whose functions include maintenance of cell polarity and tumor suppression. Hypo-expression of CADM2 gene expression has been observed in several cancers including hepatocellular carcinoma (HCC). However, the role and mechanisms of CADM2 in HCC remain unclear.<h4>Methods</h4>The expression of CADM2 and miRNA-10b (miR-10b) in HCC tissues and cell lines were detected using real-time PCR and Western blotting. Immunofluo ...[more]

PMID: 29506532

Similar Datasets

Project description:Rationale: The incidence of hepatocellular carcinoma is rising worldwide. It is predicted that nearly half of the early-stage hepatocellular carcinoma (E-HCC) patients will develop recurrence. Dysregulated pH, a hallmark of E-HCC, is correlated with poor prognosis. The acidic microenvironment has been shown to promote the release of exosomes, the membrane vesicles recognized as intercellular communicators associated with tumor progression, recurrence, and metastasis. We, therefore, aimed to identify exosomes induced by acidic microenvironment that may regulate E-HCC progression and to explore their mechanisms and clinical significance in E-HCCs. Methods: miRNA microarray analysis and LASSO logistic statistic model were used to identify the main functional exosomal miRNAs. Invasion and scratch assays were performed to examine the migration and invasion of HCC cells. Immunoblotting and immunofluorescence were employed to detect the epithelial-to-mesenchymal transition (EMT) in HCC cells. Chromatin immunoprecipitation (ChIP) was used to analyze the binding of HIF-1α and HIF-2α to promoter regions of miR-21 and miR-10b. Results: The acidic microenvironment in HCC was correlated with poor prognosis of patients. Exosomes from HCC cells cultured in the acidic medium could promote cell proliferation, migration, and invasion of recipient HCC cells. We identified miR-21 and miR-10b as the most important functional miRNAs in acidic HCC-derived exosomes. Also, the acidic microenvironment triggered the activation of HIF-1α and HIF-2α and stimulated exosomal miR-21 and miR-10b expression substantially promoting HCC cell proliferation, migration, and invasion both in vivo and in vitro. In E-HCC patients, serum exosomal miR-21 and miR-10b levels were associated with advanced tumor stage and HIF-1α and HIF-2α expression and were independent prognostic factors for disease-free survival of E-HCC patients. Most importantly, we developed a nano-drug to target exosomal miR-21 and/or miR-10b and examined its therapeutic effects against HCC in vivo. Conclusion: Our findings suggested that the exosomal miR-21 and miR-10b induced by acidic microenvironment in HCC promote cancer cell proliferation and metastasis and may serve as prognostic molecular markers and therapeutic targets for HCC.

Dataset Information

CADM2, as a new target of miR-10b, promotes tumor metastasis through FAK/AKT pathway in hepatocellular carcinoma.

Publications

CADM2, as a new target of miR-10b, promotes tumor metastasis through FAK/AKT pathway in hepatocellular carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets