1. miR-1204 promotes hepatocellular carcinoma progression through activating MAPK and c-Jun/AP1 signaling by targeting ZNF418
- Author
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Runkun Liu, Qingguang Liu, Yufeng Wang, Liankang Sun, Bowen Yao, Zhikui Liu, Tianxiang Chen, Kangsheng Tu, and Liang Wang
- Subjects
Male ,MAPK/ERK pathway ,Carcinogenesis ,Proto-Oncogene Proteins c-jun ,Apoptosis ,medicine.disease_cause ,Applied Microbiology and Biotechnology ,Mice ,Cell Movement ,miR-1204 ,3' Untranslated Regions ,Mice, Inbred BALB C ,0303 health sciences ,Liver Neoplasms ,c-jun ,hepatocellular carcinoma ,Middle Aged ,Prognosis ,AP-1 transcription factor ,Disease Progression ,Female ,Signal Transduction ,Research Paper ,Adult ,Carcinoma, Hepatocellular ,Cell Survival ,MAP Kinase Signaling System ,ZNF418 ,Mice, Nude ,Biology ,03 medical and health sciences ,Cell Line, Tumor ,microRNA ,Biomarkers, Tumor ,medicine ,Animals ,Humans ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Aged ,Cell Proliferation ,030304 developmental biology ,Oncogene ,Cell growth ,c-Jun ,Cell Biology ,MAPK ,digestive system diseases ,Repressor Proteins ,MicroRNAs ,Tumor progression ,Cancer research ,Neoplasm Transplantation ,Developmental Biology - Abstract
Emerging evidence has indicated that abnormal microRNAs (miRNAs) participated in carcinogenesis and tumor progression in hepatocellular carcinoma (HCC). Better understanding the association between miRNAs and HCC may contribute to discover novel therapeutic approaches for diagnosis and treatments. In the current study, we have shown that miR-1204 level was elevated in HCC tissues and cell lines, which was associated with malignant clinical features, including large tumor size and advanced TNM stage. Furthermore, gain-or loss-of function assays demonstrated that miR-1204 promoted cell proliferation in vitro and tumor growth in vivo as well as inhibited apoptosis in vitro. Luciferase reporter gene assays confirmed that ZNF418 was a direct downstream target of miR-1204. Recuse assays showed that ZNF418 mediates the biological function of miR-1204 on HCC cells through regulating MAPK and c-Jun signaling. In conclusion, our results suggest that miR-1204 functions as an oncogene to promote proliferation and inhibit apoptosis through regulating MAPK and c-Jun signaling by targeting ZNF418, and potentially serves as a novel prognostic biomarker and therapeutic target for HCC.
- Published
- 2019