miR-515–5p suppresses HCC migration and invasion via targeting IL6/JAK/STAT3 pathway
| Autor: | Hao Zheng, Yuan-ping Tao, Weiping Zhou, Zhen-guang Wang, Jun-sheng Ni, Yang-liu Ou, Li-hua Song, Hong-Li Yan |
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| Rok vydání: | 2020 |
| Předmět: |
Male
STAT3 Transcription Factor 0301 basic medicine Carcinoma Hepatocellular Mice Nude Apoptosis Stat3 Signaling Pathway Mice 03 medical and health sciences 0302 clinical medicine Cell Movement microRNA Biomarkers Tumor Tumor Cells Cultured Animals Humans Medicine Interleukin 6 STAT3 Cell Proliferation Gene knockdown biology Interleukin-6 business.industry Liver Neoplasms Cell migration Janus Kinase 1 Middle Aged Prognosis Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic Survival Rate MicroRNAs 030104 developmental biology Oncology 030220 oncology & carcinogenesis biology.protein Cancer research Female Surgery Signal transduction Janus kinase business |
| Zdroj: | Surgical Oncology. 34:113-120 |
| ISSN: | 0960-7404 |
| DOI: | 10.1016/j.suronc.2020.03.003 |
| Popis: | MicroRNAs (miRNAs) have been identified as critical modulators of cell migration and invasion, which are the major causes of cancer progression including hepatocellular carcinoma (HCC). However, the accurate role of miR-515–5p in HCC is still uncertain. Here, we report that miR-515–5p expression is down-regulated in HCC tissues and cell lines, and associated with absence of capsule formation (p = 0.015)﹑microvascular invasion(p = 0.003)﹑and advantange TNM stage (II-III) (p = 0.014) in HCC patients. Overexpression of miR-515–5p inhibited migration and invasion of HCC cells in vitro and in vivo, while miR-515–5p knockdown has the inverse effect. Moreover, using miRNA databases and dual-luciferase report assay, we find miR-515–5p directly binds to the 3′-untranslated region (3′-UTR) of interleukin 6 (IL6). In addition, the regulatory association between miR-515–5p and the IL-6/Janus kinase (JNK)/signal transducer and activator of transcription-3 (STAT3) signaling pathway was explored. Furthermore, overexpression of miR-515–5p inhibited the activation of the JAK/STAT3 signaling pathway, which was rescued by overexpression of IL-6. The results of the current study indicate that miR-515–5p overexpression may serve an important role in inhibiting migration and invasion of HCC cells via suppression of IL-6/JAK/STAT3 signaling pathway activation. MiR-515–5p may serve as a potential therapeutic target for HCC. |
| Databáze: | OpenAIRE |
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