title: Minicircle-oriP-miR-31 as a Novel EBNA1-Specific miRNA Therapy Approach for Nasopharyngeal Carcinoma.
abstract: MicroRNAs (miRNAs) are important post-transcriptional regulators that control cancer development and progression. However, the application of miRNA therapy in cancer has been hampered by a lack of an efficient and targeted delivery system. In our previous studies, an oriP promoter-based minicircle system successfully mediated targeted foreign gene expression in EBNA1-positive nasopharyngeal carcinoma (NPC). However, it remains to be evaluated whether this system can be applied for tumor miRNA therapy. miR-31-5p, a tumor suppressive miRNA involved in the tumorigenesis of EBV-positive NPC, was selected as the therapeutic miRNA to be transferred. In this work, we constructed a novel EBNA1-specific miRNA expression system, minicircle-oriP-miR-31. The results indicated that mc-oriP-miR-31 mediated selective miR-31-5p expression in EBNA1-positive NPC cells. Both the proliferation and migration of EBNA1-positive NPC cell lines were inhibited by mc-oriP-miR-31 treatment in vitro. Furthermore, mc-oriP-miR-31 treatment inhibited xenograft growth and lung metastasis in vivo. We also identified WDR5 as a novel miR-31-5p target. Knockdown of WDR5 inhibited NPC cell proliferation and migration and was associated with downregulation of Notch1. Reintroduction of WDR5 partially abrogated the suppressive effects induced by miR-31-5p. In conclusion, we demonstrate for the first time that targeted expression of miR-31-5p using a nonviral minicircle vector can serve as a novel approach for tumor miRNA therapy. Moreover, WDR5 may be a promising therapeutic target for NPC treatment.
authors.affiliation: 1 State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center , Guangzhou, China .|2 Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center , Guangzhou, China .
authors.forename: Jiangxue
authors.initials: J
authors.lastname: Wu
authors.affiliation: 1 State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center , Guangzhou, China .|2 Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center , Guangzhou, China .
authors.forename: Xin
authors.initials: X
authors.lastname: Tan
authors.affiliation: 1 State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center , Guangzhou, China .|2 Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center , Guangzhou, China .
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Lin
authors.affiliation: 1 State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center , Guangzhou, China .|2 Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center , Guangzhou, China .
authors.forename: Luping
authors.initials: L
authors.lastname: Yuan
authors.affiliation: 1 State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center , Guangzhou, China .|2 Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center , Guangzhou, China .
authors.forename: Jiemin
authors.initials: J
authors.lastname: Chen
authors.affiliation: 1 State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center , Guangzhou, China .|2 Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center , Guangzhou, China .
authors.forename: Lin
authors.initials: L
authors.lastname: Qiu
authors.affiliation: 1 State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center , Guangzhou, China .|2 Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center , Guangzhou, China .
authors.forename: Wenlin
authors.initials: W
authors.lastname: Huang
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000627:therapeutic use; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000627:therapeutic use; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051881:Receptor, Notch1 / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D019309:Epstein-Barr Virus Nuclear Antigens; D047908:Intracellular Signaling Peptides and Proteins; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D051881:Receptor, Notch1; C502547:WDR5 protein, human; D011495:Histone-Lysine N-Methyltransferase; C417029:EBV-encoded nuclear antigen 1
keywords: WDR5; miR-31-5p; minicircle; nasopharyngeal carcinoma; oriP