MiR-6875-3p promotes the proliferation, invasion and metastasis of hepatocellular carcinoma via BTG2/FAK/Akt pathway.

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  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 8308647 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-9966 (Electronic) Linking ISSN: 03929078 NLM ISO Abbreviation: J Exp Clin Cancer Res Subsets: MEDLINE
    • Publication Information:
      Publication: 2009- : London : BioMed Central
      Original Publication: [Roma] : APSIT,
    • Subject Terms:
      Carcinoma, Hepatocellular/*genetics ; Focal Adhesion Kinase 1/*metabolism ; Immediate-Early Proteins/*metabolism ; Liver Neoplasms/*genetics ; MicroRNAs/*biosynthesis ; Proto-Oncogene Proteins c-akt/*metabolism ; Tumor Suppressor Proteins/*metabolism; Animals ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/pathology ; Cell Line, Tumor ; Cell Proliferation/physiology ; Down-Regulation ; Focal Adhesion Kinase 1/biosynthesis ; Focal Adhesion Kinase 1/genetics ; Hep G2 Cells ; Heterografts ; Humans ; Immediate-Early Proteins/biosynthesis ; Immediate-Early Proteins/genetics ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Signal Transduction ; Transfection ; Tumor Suppressor Proteins/biosynthesis ; Tumor Suppressor Proteins/genetics
    • Abstract:
      Background: Increasing evidence supports the association of microRNA with tumor occurrence and development. However, the expression of miR-6875-3p and its role in cell proliferation, invasion and metastasis in hepatocellular carcinoma (HCC) remains elusive.
      Methods: The expression of miR-6875-3p and BTG2 in HCC tissues and cell lines was detected by using in situ hybridization, immunohistochemistry and qRT-PCR, respectively. A western blot assay, qRT-PCR and Luciferase reporter assay were employed to study the interaction between miR-6875-3p and BTG2. Cell proliferation invasion and metastasis were measured by MTT, transwell and matrigel analyses in vitro. In vivo, tumorigenicity and metastasis assays were performed in nude mice.
      Results: We found that miR-6875-3p were elevated expressed in HCC tissues and cell lines, and negatively correlated with BTG2 expression, while positively correlated with tumor staging, size, degree of differentiation, and vascular invasion of HCC. Moreover, in vitro and in vivo assays showed that miR-6875-3p regulates EMT and improve the proliferation, metastasis and stem cell-like properties of HCC cells. BTG2 was identified as a direct and functional target of miR-6875-3p via the 3'-UTR of BTG2. We also confirmed that miR-6875-3p plays its biological functions via the BTG2/FAK/Akt pathway.
      Conclusion: Our study provides evidence that high expression of miR-6875-3p can promote tumorigenesis of HCC in vitro and in vivo, so as to function as a novel oncogene in HCC. In mechanism, we found that miR-6875-3p plays its biological functions via the BTG2/FAK/Akt pathway.
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    • Grant Information:
      Grand No. 20152027 The Basic Research Program of Health Planning Commission Foundation of Jilin Province; Grand No. 3D5177793429 the Special Health Foundation of Jilin Province; Grand No. 20170204046SF the Social Development Foundation of Science and Technology Department of Jilin Province
    • Contributed Indexing:
      Keywords: BTG2; HCC; Invasion; Metastasis; Proliferation; miR-6875-3p
    • Accession Number:
      0 (Immediate-Early Proteins)
      0 (MicroRNAs)
      0 (Mirn6875 microRNA, human)
      0 (Tumor Suppressor Proteins)
      141490-22-4 (BTG2 protein, human)
      EC 2.7.10.2 (Focal Adhesion Kinase 1)
      EC 2.7.10.2 (PTK2 protein, human)
      EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
    • Publication Date:
      Date Created: 20190110 Date Completed: 20190219 Latest Revision: 20200225
    • Publication Date:
      20240829
    • Accession Number:
      PMC6323674
    • Accession Number:
      10.1186/s13046-018-1020-z
    • Accession Number:
      30621734