Frontiers in Oncology (Jan 2020)
Overexpression of IGF2BP3 as a Potential Oncogene in Ovarian Clear Cell Carcinoma
- Huidi Liu,
- Huidi Liu,
- Huidi Liu,
- Huidi Liu,
- Huidi Liu,
- Zheng Zeng,
- Zheng Zeng,
- Zheng Zeng,
- Mitra Afsharpad,
- Caiji Lin,
- Caiji Lin,
- Caiji Lin,
- Siwen Wang,
- Siwen Wang,
- Siwen Wang,
- Hao Yang,
- Shuhong Liu,
- Linda E. Kelemen,
- Wenwen Xu,
- Wenwen Xu,
- Wenwen Xu,
- Wenqing Ma,
- Wenqing Ma,
- Wenqing Ma,
- Qian Xiang,
- Qian Xiang,
- Qian Xiang,
- Emilio Mastriani,
- Emilio Mastriani,
- Emilio Mastriani,
- Pengfei Wang,
- Pengfei Wang,
- Pengfei Wang,
- Jiali Wang,
- Jiali Wang,
- Jiali Wang,
- Shu-Lin Liu,
- Shu-Lin Liu,
- Shu-Lin Liu,
- Shu-Lin Liu,
- Randal N. Johnston,
- Randal N. Johnston,
- Martin Köbel,
- Martin Köbel
Affiliations
- Huidi Liu
- Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, China
- Huidi Liu
- HMU-UCCSM Centre for Infection and Genomics, Harbin, China
- Huidi Liu
- Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China
- Huidi Liu
- Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada
- Huidi Liu
- Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada
- Zheng Zeng
- Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, China
- Zheng Zeng
- HMU-UCCSM Centre for Infection and Genomics, Harbin, China
- Zheng Zeng
- Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China
- Mitra Afsharpad
- Pathology and Laboratory Medicine, Calgary Laboratory Service, University of Calgary, Calgary, AB, Canada
- Caiji Lin
- Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, China
- Caiji Lin
- HMU-UCCSM Centre for Infection and Genomics, Harbin, China
- Caiji Lin
- Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China
- Siwen Wang
- Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, China
- Siwen Wang
- HMU-UCCSM Centre for Infection and Genomics, Harbin, China
- Siwen Wang
- Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China
- Hao Yang
- Department of Pathology, Harbin Chest Hospital, Harbin, China
- Shuhong Liu
- Pathology and Laboratory Medicine, Calgary Laboratory Service, University of Calgary, Calgary, AB, Canada
- Linda E. Kelemen
- Hollings Cancer Center and Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, United States
- Wenwen Xu
- Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, China
- Wenwen Xu
- HMU-UCCSM Centre for Infection and Genomics, Harbin, China
- Wenwen Xu
- Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China
- Wenqing Ma
- Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, China
- Wenqing Ma
- HMU-UCCSM Centre for Infection and Genomics, Harbin, China
- Wenqing Ma
- Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China
- Qian Xiang
- Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, China
- Qian Xiang
- HMU-UCCSM Centre for Infection and Genomics, Harbin, China
- Qian Xiang
- Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China
- Emilio Mastriani
- Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, China
- Emilio Mastriani
- HMU-UCCSM Centre for Infection and Genomics, Harbin, China
- Emilio Mastriani
- Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China
- Pengfei Wang
- Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, China
- Pengfei Wang
- HMU-UCCSM Centre for Infection and Genomics, Harbin, China
- Pengfei Wang
- Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China
- Jiali Wang
- Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, China
- Jiali Wang
- HMU-UCCSM Centre for Infection and Genomics, Harbin, China
- Jiali Wang
- Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China
- Shu-Lin Liu
- Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, China
- Shu-Lin Liu
- HMU-UCCSM Centre for Infection and Genomics, Harbin, China
- Shu-Lin Liu
- Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China
- Shu-Lin Liu
- Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, Canada
- Randal N. Johnston
- Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada
- Randal N. Johnston
- Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada
- Martin Köbel
- Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada
- Martin Köbel
- Pathology and Laboratory Medicine, Calgary Laboratory Service, University of Calgary, Calgary, AB, Canada
- DOI
- https://doi.org/10.3389/fonc.2019.01570
- Journal volume & issue
-
Vol. 9
Abstract
Ovarian Clear Cell Carcinoma (OCCC) displays distinctive clinical and molecular characteristics and confers the worst prognosis among all ovarian carcinoma histotypes when diagnosed at advanced stage, because of the lack of effective therapy. IGF2BP3 is an RNA binding protein that modulates gene expression by post-transcriptional action. In this study, we investigated the roles of IGF2BP3 in the progression of OCCC. We used 328 OCCCs from the AOVT (the Alberta Ovarian Tumor Type study) and the COEUR (the Canadian Ovarian Experimental Unified Resource) cohorts to elucidate the associations between IGF2BP3 expression and clinicopathological parameters, with positive IGF2BP3 expression defined as diffuse block staining, being more frequently observed at stage III (P = 0.0056) and significantly associated with unfavorable overall survival (HR = 1.59, 95% CI 1.09–2.33) in multivariate analysis. IGF2BP3 mRNA gene expression was markedly increased in OCCC cell lines compared to normal tissues such as ovarian surface epithelium. We chose two IGF2BP3-overexpressing cell lines ES2 and OVMANA for in vitro and in vivo knockdown experiments. The proliferation and viability of both cell lines were significantly inhibited by two IGF2BP3 siRNAs and similar suppression was observed in cell migration and invasion by Wound Healing and Transwell assays. The percentage of apoptotic cancer cells was enhanced by both IGF2BP3 siRNAs. In vivo experiments showed significantly reduced sizes of tumors when treated with IGF2BP3 siRNA compared to controls. Furthermore, cancer metastasis-indicators MMP2 and MMP9 proteins were down-regulated. In conclusion, our study shows that IGF2BP3 expression is a promising biomarker for prognostication of women diagnosed with OCCC with multiple effects on key cell functions, supporting its role as an important cellular regulator with potential oncogenic activity, and as a potential target for future intervention strategies.
Keywords
