LncRNA DBH-AS1 facilitates the tumorigenesis of hepatocellular carcinoma by targeting miR-138 via FAK/Src/ERK pathway - 20/09/18
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Abstract |
Background |
It has been reported that dysregulated lncRNAs are associated with the pathogenesis of human tumors including hepatocellular carcinoma (HCC). LncRNA DBH-AS1 was reported to be an oncogene in HCC. However, the molecular mechanisms of DBH-AS1 in HCC progression are largely undefined.
Methods |
The expressions of DBH-AS1 and miR-138 in HCC tissues and cells were examined by qRT-PCR. The effects of DBH-AS1 and miR-138 on cell viability, colony formation, apoptosis, and FAK/Src/ERK signaling pathway were determined by CCK-8, colony formation, flow cytometry, and western blot analyses, respectively. Luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to explore the interaction between miR-138 and DBH-AS1. Tumor xenograft assay was performed to confirm the function and mechanism of DBH-AS1 in the progression of HCC in vivo.
Results |
DBH-AS1 expression was upregulated and miR-138 expression was downregulated in HCC tissues and cells. DBH-AS1 silencing and miR-138 overexpression reduced cell viability, inhibited colony formation, and induced apoptosis. Moreover, DBH-AS1 acted as a molecular sponge of miR-138 to downregulate miR-138 expression. Also, DBH-AS1 overexpression attenuated miR-138-mediated anti-proliferation and pro-apoptosis effects. Additionally, miR-138 overexpression gave rise to a blockage on FAK/Src/ERK pathway, while this effect was undermined by increased DBH-AS1. Furthermore, DBH-AS1 promoted tumor growth and induced the activation of FAK/Src/ERK pathway by targeting miR-138 in vivo.
Conclusion |
DBH-AS1 facilitated the development of HCC via miR-138/FAK/Src/ERK pathway, establishing the molecular basis of DBH-AS1 in clinical application for HCC.
Le texte complet de cet article est disponible en PDF.Keywords : lncRNA, DBH-AS1, miR-138, FAK/Src/ERK, Hepatocellular carcinoma
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Vol 107
P. 824-833 - novembre 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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