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

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

  • J Exp Clin Cancer Res. 2018 Mar 5;37(1):46. doi: 10.1186/s13046-018-0699-1.
Dongliang Li 1 Yongjian Zhang 2 He Zhang 1 Chao Zhan 2 Xin Li 3 Tu Ba 4 Zini Qiu 1 Fang E 1 Guixiang Lv 1 Chendan Zou 1 Chuxuan Wang 1 Lining Si 1 5 Chaoxia Zou 6 7 Qiang Li 8 Xu Gao 9 10 11
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang, 150081, China.
  • 2 Department of Hepatobiliary and Pancreas, Heilongjiang Cancer Hospital, Harbin, China.
  • 3 Department of Respiratory Medical Oncology, Heilongjiang Cancer Hospital, Harbin, China.
  • 4 Department of Neck and Breast Surgery, Mudanjiang Tumor Hospital, Mudanjiang, China.
  • 5 Department of Critical-care Medicine, the Affiliated Hospital of Qinghai University, Xining, Qinghai, China.
  • 6 Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang, 150081, China. [email protected].
  • 7 Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medicine Sciences, Harbin, Heilongjiang, 150081, China. [email protected].
  • 8 Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China. [email protected].
  • 9 Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang, 150081, China. [email protected].
  • 10 Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medicine Sciences, Harbin, Heilongjiang, 150081, China. [email protected].
  • 11 Key Laboratory of Cardiovascular Medicine Research of Harbin Medical University, Ministry of Education, Harbin, China. [email protected].
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.

Keywords

Cell adhesion molecule 2; Epithelial-mesenchymal transition; Hepatocellular carcinoma; MicroRNA-10b; Tumor metastasis.

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