MiRNA expression profiles reveal the involvement of miR-26a, miR-548l and miR-34a in hepatocellular carcinoma progression through regulation of ST3GAL5
| Autor: | Li Jia, Nana Li, Lifen Zhao, Yuan Miao, Huimin Zhou, Hongjiao Cai |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Carcinoma Hepatocellular Mice Nude Biology Pathology and Forensic Medicine Metastasis law.invention Mice Young Adult 03 medical and health sciences 0302 clinical medicine In vivo law Cell Line Tumor microRNA medicine Animals Humans Molecular Biology Gene Aged Gene Expression Profiling Liver Neoplasms Cell Biology Middle Aged medicine.disease Sialyltransferases In vitro MicroRNAs 030104 developmental biology Tissue Array Analysis 030220 oncology & carcinogenesis Hepatocellular carcinoma Cancer research Suppressor Female DNA microarray |
| Zdroj: | Laboratory Investigation. 97:530-542 |
| ISSN: | 0023-6837 |
| DOI: | 10.1038/labinvest.2017.12 |
| Popis: | MicroRNAs (miRNAs) have key roles in comprehensive physiological and pathological processes by targeting specific genes through translational repression. Identification of miRNAs related to metastasis enables us to obtain better insight into cancer development. In the current study, we investigated the miRNA expressional profiles in the highly invasive human hepatocellular carcinoma cell line MHCC97-H and MHCC97-L with lower metastatic potential using miRNA microarrays. By quantitative real-time PCR, we confirmed the results of miRNA experiments. Thirteen differentially expressed miRNAs were identified between MHCC97-H and MHCC97-L cells; and the same results were found in clinical samples. Using bioinformatic analysis and luciferase reporter assay, we found that ST3GAL5, a sialyltransferase gene, was the direct target of miR-26a, miR-548l and miR-34a. Engineered expression of miR-26a, miR-548l or miR-34a in MHCC97-H or MHCC97-L cells could significantly change their malignant behaviors and oncogenicity in in vitro and in vivo assays. Manipulated expression of ST3GAL5 also led to the alteration of the metastatic potential of MHCC97-H and MHCC97-L cells, in agreement with the effects of above three miRNAs. Altogether, our data indicate that the levels of these miRNAs may be used as biological markers for evaluating hepatocellular carcinoma progression. miR-26a, miR-548l and miR-34a, acting as tumor suppressors, may exert their effects by regulating ST3GAL5. |
| Databáze: | OpenAIRE |
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