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KDM4B-mediated epigenetic silencing of miRNA-615-5p augments RAB24 to facilitate malignancy of hepatoma cells

Emerging evidence indicates that dysregulation of microRNAs (miRNAs) contributes to hepatocellular carcinoma (HCC) tumorigenesis and development. Here, we found that miR-615-5p was obviously downregulated in HCC. Furthermore, the deficiency of demethylase KDM4B stimulated the CpG methylation of miR-...

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Detalles Bibliográficos
Autores principales: Chen, Zheng, Wang, Xiangling, Liu, Ruiyan, Chen, Lin, Yi, Jianying, Qi, Bing, Shuang, Zeyu, Liu, Min, Li, Xin, Li, Shengping, Tang, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392280/
https://www.ncbi.nlm.nih.gov/pubmed/27487123
http://dx.doi.org/10.18632/oncotarget.10832
Descripción
Sumario:Emerging evidence indicates that dysregulation of microRNAs (miRNAs) contributes to hepatocellular carcinoma (HCC) tumorigenesis and development. Here, we found that miR-615-5p was obviously downregulated in HCC. Furthermore, the deficiency of demethylase KDM4B stimulated the CpG methylation of miR-615-5p promoter and then decreased the miR-615-5p expression. The Ras-related protein RAB24 was found to be downregulated by miR-615-5p. The low level of miR-615-5p increased the expression of RAB24 and facilitated HCC growth and metastasis in vitro and in vivo. Moreover, miR-615-5p suppresses HCC cell growth by influencing cell cycle progression and apoptosis. Downregulation of miR-615-5p and upregulation of RAB24 promotes the epithelial-mesenchymal transition (EMT), adhesion and vasculogenic mimicry (VM) of HCC cells, all of which contribute to cell motility and metastasis. Thus, miR-615-5p, who is downregulated by KDM4B-mediated hypermethylation in its promoter, functions as a tumor suppressor by inhibiting RAB24 expression in HCC. In conclusion, our findings characterize miR-615-5p as an important epigenetically silenced miRNA involved in the Rab-Ras pathway in hepatocellular carcinoma and expand our understanding of the molecular mechanism underlying hepatocarcinogenesis and metastasis.