Overexpression of IGF2BP3 as a Potential Oncogene in Ovarian Clear Cell Carcinoma
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 exp...
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| Language: | English |
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Frontiers Media S.A.
2020-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.01570/full |
| _version_ | 1819097929549348864 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Huidi Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T00:22:54Z |
| format | Article |
| id | doaj.art-5754b0e6da5343738e7814daee46cf15 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-22T00:22:54Z |
| publishDate | 2020-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-5754b0e6da5343738e7814daee46cf152022-12-21T18:45:07ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-01-01910.3389/fonc.2019.01570484710Overexpression of IGF2BP3 as a Potential Oncogene in Ovarian Clear Cell CarcinomaHuidi Liu0Huidi Liu1Huidi Liu2Huidi Liu3Huidi Liu4Zheng Zeng5Zheng Zeng6Zheng Zeng7Mitra Afsharpad8Caiji Lin9Caiji Lin10Caiji Lin11Siwen Wang12Siwen Wang13Siwen Wang14Hao Yang15Shuhong Liu16Linda E. Kelemen17Wenwen Xu18Wenwen Xu19Wenwen Xu20Wenqing Ma21Wenqing Ma22Wenqing Ma23Qian Xiang24Qian Xiang25Qian Xiang26Emilio Mastriani27Emilio Mastriani28Emilio Mastriani29Pengfei Wang30Pengfei Wang31Pengfei Wang32Jiali Wang33Jiali Wang34Jiali Wang35Shu-Lin Liu36Shu-Lin Liu37Shu-Lin Liu38Shu-Lin Liu39Randal N. Johnston40Randal N. Johnston41Martin Köbel42Martin Köbel43Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, ChinaHMU-UCCSM Centre for Infection and Genomics, Harbin, ChinaTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, ChinaDepartment of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, CanadaArnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, CanadaGenomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, ChinaHMU-UCCSM Centre for Infection and Genomics, Harbin, ChinaTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, ChinaPathology and Laboratory Medicine, Calgary Laboratory Service, University of Calgary, Calgary, AB, CanadaGenomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, ChinaHMU-UCCSM Centre for Infection and Genomics, Harbin, ChinaTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, ChinaGenomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, ChinaHMU-UCCSM Centre for Infection and Genomics, Harbin, ChinaTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, ChinaDepartment of Pathology, Harbin Chest Hospital, Harbin, ChinaPathology and Laboratory Medicine, Calgary Laboratory Service, University of Calgary, Calgary, AB, CanadaHollings Cancer Center and Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, United StatesGenomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, ChinaHMU-UCCSM Centre for Infection and Genomics, Harbin, ChinaTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, ChinaGenomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, ChinaHMU-UCCSM Centre for Infection and Genomics, Harbin, ChinaTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, ChinaGenomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, ChinaHMU-UCCSM Centre for Infection and Genomics, Harbin, ChinaTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, ChinaGenomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, ChinaHMU-UCCSM Centre for Infection and Genomics, Harbin, ChinaTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, ChinaGenomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, ChinaHMU-UCCSM Centre for Infection and Genomics, Harbin, ChinaTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, ChinaGenomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, ChinaHMU-UCCSM Centre for Infection and Genomics, Harbin, ChinaTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, ChinaGenomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, ChinaHMU-UCCSM Centre for Infection and Genomics, Harbin, ChinaTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, ChinaDepartment of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, CanadaDepartment of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, CanadaArnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, CanadaArnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, CanadaPathology and Laboratory Medicine, Calgary Laboratory Service, University of Calgary, Calgary, AB, CanadaOvarian 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.https://www.frontiersin.org/article/10.3389/fonc.2019.01570/fullovarian cancerclear cell carcinomaIGF2BP3IMP3prognosismetastasis |
| spellingShingle | 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 Overexpression of IGF2BP3 as a Potential Oncogene in Ovarian Clear Cell Carcinoma Frontiers in Oncology ovarian cancer clear cell carcinoma IGF2BP3 IMP3 prognosis metastasis |
| title | Overexpression of IGF2BP3 as a Potential Oncogene in Ovarian Clear Cell Carcinoma |
| title_full | Overexpression of IGF2BP3 as a Potential Oncogene in Ovarian Clear Cell Carcinoma |
| title_fullStr | Overexpression of IGF2BP3 as a Potential Oncogene in Ovarian Clear Cell Carcinoma |
| title_full_unstemmed | Overexpression of IGF2BP3 as a Potential Oncogene in Ovarian Clear Cell Carcinoma |
| title_short | Overexpression of IGF2BP3 as a Potential Oncogene in Ovarian Clear Cell Carcinoma |
| title_sort | overexpression of igf2bp3 as a potential oncogene in ovarian clear cell carcinoma |
| topic | ovarian cancer clear cell carcinoma IGF2BP3 IMP3 prognosis metastasis |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.01570/full |
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