期刊
BIOMATERIALS
卷 192, 期 -, 页码 590-600出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2018.11.035
关键词
miR-212; Nanoparticle; USP9X; Doxorubicin; PDAC
资金
- National High Technology Research and Development Program of China [SS2015AA020405, SS2014AA020533]
- Zhejiang Provincial Natural Science Foundation of China [LQ13H160006]
- Key Innovative Team for the Diagnosis and Treatment of Pancreatic Cancer of Zhejiang Province [2013TD06]
- National Natural Science Foundation of China [81302071, 81401954, 81530079]
Pancreatic ductal adenocarcinoma (PDAC) is a destructive cancer with poor prognosis. Both novel therapeutic targets and approaches are needed to improve the overall survival of PDAC patients. MicroRNA-212 (miR-212) has been reported as a tumor suppressor in multiple cancers, but its definitive role and exact mechanism in the progression of pancreatic cancer is unclear. In this study, we developed a new chimeric peptide (PL-1) composed of plectin-l-targeted PDAC-specific and arginine-rich RNA-binding motifs which could condense miRNA to self assemble supramolecular nanoparticles. These nanoparticles could deliver miR-212 into PDAC cells specifically and efficiently which also showed good stability in RNase and serum. Moreover, we demonstrated that PL-1/miR-212 nanoparticles could dramatically enhance the chemotherapeutic effect of doxorubicin for PDAC both in vitro and in vivo. In terms of mechanism, combined miR-212 intervention by PL-1/miR-212 nanoparticles resulted in obvious decrease of USP9X expression (ubiquitin specific peptidase 9, X-linked, USP9X) and eventually enhanced the doxorubicin induced apoptosis and autophagy of PDAC cells. These findings provide a new promising anti-cancer strategy via PL-1/miR-212 nanoparticles and identify miR-212/USP9X as a new potential target for future systemic therapy against human PDAC.
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