Anti-miR182 reduces ovarian cancer burden, invasion, and metastasis: an in vivo study in orthotopic xenografts of nude mice.
High-grade serous ovarian carcinoma (HGSOC) is a fatal disease, and its grave outcome is largely because of widespread metastasis at the time of diagnosis. Current chemotherapies reduce tumor burden, but they do not provide long-term benefits for patients with cancer. The aggressive tumor growth and metastatic behavior characteristic of these tumors demand novel treatment options such as anti-microRNA treatment, which is emerging as a potential modality for cancer therapy. MicroRNA-182 (miR182) overexpression contributes to aggressive ovarian cancer, largely by its negative regulation of multiple tumor suppressor genes involved in tumor growth, invasion, metastasis, and DNA instability. In this study, we examined the therapeutic potential of anti-miR182 utilizing the animal orthotopic model to mimic human ovarian cancer using ovarian cancer cells SKOV3 (intrabursal xenografts) and OVCAR3 (intraperitoneal injection). These models provide a valuable model system for the investigation of ovarian cancer therapy in vivo. Through a combination of imaging, histological, and molecular analyses, we found that anti-miR182 treatment can significantly reduce tumor burden (size), local invasion, and distant metastasis compared with its control in both models. The bases of anti-miR182 treatment are mainly through the restoration of miR182 target expression, including but not limited to BRCA1, FOXO3a, HMGA2, and MTSS1. Overall, our results strongly suggest that anti-miR182 can potentially be used as a therapeutic modality in treating HGSOC.
Authors' Affiliations: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University; Pathology and.
Xiaofei
X
Xu
Pathology and.
Bushra
B
Ayub
Institute of Genetics, Shandong University School of Medicine, Jinan, Shandong, China; Departments of Pathology and.
Zhaojian
Z
Liu
Obstetrics and Gynecology;
Vanida Ann
VA
Serna
Pathology and Obstetrics and Gynecology; Robert H. Lurie Comprehensive Cancer Center, Northwestern University School of Medicine, Chicago, Illinois;
Wenan
W
Qiang
Pathology and.
Yugang
Y
Liu
Department of Pathology, New York University, New York, New York; and.
Eva
E
Hernando
Regulus Therapeutic, San Diego, California.
Sonya
S
Zabludoff
Obstetrics and Gynecology; Robert H. Lurie Comprehensive Cancer Center, Northwestern University School of Medicine, Chicago, Illinois;
Takeshi
T
Kurita
Authors' Affiliations: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University; kongbeihua@sdu.edu.cn jianjun-wei@northwestern.edu.
Beihua
B
Kong
Pathology and Obstetrics and Gynecology; Robert H. Lurie Comprehensive Cancer Center, Northwestern University School of Medicine, Chicago, Illinois; kongbeihua@sdu.edu.cn jianjun-wei@northwestern.edu.
Jian-Jun
JJ
Wei
D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008163:Luminescent Measurements / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D011897:Random Allocation; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D035683:MicroRNAs; C538984:Mirn182 microRNA, human