Dysbindin promotes pancreatic ductal adenocarcinoma metastasis by activating NF-κB/MDM2 via miR-342-3p
| Autor: | Yong Chen, Dan-Dan Han, Xin Guo, Mingyao Tang, Cheng Fang, Donglie Zhu, Xuebiao Yao, Shi Zheng, Yongzhan Nie, Hang Fu, Ning Xie, Mingzuo Jiang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Cancer Research endocrine system diseases medicine.medical_treatment Mice Nude Kaplan-Meier Estimate Targeted therapy Metastasis 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cell Movement Cell Line Tumor microRNA medicine Animals Humans PI3K/AKT/mTOR pathway Aged biology Cell growth Dysbindin NF-kappa B Proto-Oncogene Proteins c-mdm2 Middle Aged medicine.disease Xenograft Model Antitumor Assays digestive system diseases Gene Expression Regulation Neoplastic Pancreatic Neoplasms MicroRNAs 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research biology.protein Mdm2 Female Carcinoma Pancreatic Ductal |
| Zdroj: | Cancer letters. 477 |
| ISSN: | 1872-7980 |
| Popis: | Pancreatic ductal adenocarcinoma (PDAC) is one of the most invasive solid tumours and has the highest cancer-related mortality rate. Despite intense investigation, the molecular mechanisms underlying the invasiveness and aetiology of PDAC remain elusive. MicroRNAs (miRNAs) are key regulators of tumour cell plasticity, but their roles in PDAC metastasis have not been characterized. Our early studies showed that dysbindin protein levels are elevated in PDAC patients compared with control individuals and that dysbindin upregulation elicits PDAC cell proliferation via the PI3K pathway. Here, we show that dysbindin promoted PDAC metastasis via the NF-κB/MDM2 signalling axis. Increased dysbindin levels correlated with aggressive features in PDAC, and the overexpression of dysbindin significantly promoted PDAC metastasis and invasion in vitro and in vivo. Surprisingly, dysbindin was identified as a direct target of miR-342-3p, which promotes NF-κB activation and PDAC metastasis. Thus, dysbindin-mediated NF-κB activation via miR-342-3p represents a context-dependent switch that enables PDAC cell proliferation and metastasis. Our data suggest that dysbindin and miR-342-3p are potential leads for the development of targeted therapy for PDAC. |
| Databáze: | OpenAIRE |
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