Youqin Xu1,2,3, Wancheng Chen2,3, Jing Liang4, Xiaoqi Zeng5, Kaiyuan Ji6, Jianlong Zhou2,3, Shijun Liao5, Jiexian Wu1, Kongyang Xing1, Zilong He7, Yang Yang2,3, Qianzhen Liu8, Pingyi Zhu1, Yuchang Liu1, Li Li1, Minfeng Liu9, Wenxiao Chen10, Wenhua Huang11,12,13,14. 1. Taishan People's Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Taishan, 529200, China. 2. National Key Discipline of Human Anatomy, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, China. 3. Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, 524001, China. 4. School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China. 5. Breast Center, Department of general surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. 6. The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518000, China. 7. Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. 8. Department of Pathology, School of Basic Medicine, Guangdong Medical University, Zhanjiang, 524023, China. 9. Breast Center, Department of general surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. matthewliu007@163.com. 10. Taishan People's Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Taishan, 529200, China. 602607747@qq.com. 11. Taishan People's Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Taishan, 529200, China. huangwenhua2009@139.com. 12. National Key Discipline of Human Anatomy, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, China. huangwenhua2009@139.com. 13. Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, 524001, China. huangwenhua2009@139.com. 14. Department of Pathology, School of Basic Medicine, Guangdong Medical University, Zhanjiang, 524023, China. huangwenhua2009@139.com.
Abstract
BACKGROUND: Phosphatidylinositol-4-phosphate-binding protein GOLPH3L is overexpressed in human ductal carcinoma of the breast, and its expression levels correlate with the prognosis of breast cancer patients. However, the roles of GOLPH3L in breast tumorigenesis remain unclear. METHODS: We assessed the expression and biological function of GOLPH3L in breast cancer by combining bioinformatic prediction, metabolomics analysis and RNA-seq to determine the GOLPH3L-related pathways involved in tumorigenesis. Dual-luciferase reporter assay and coimmunoprecipitation (Co-IP) were used to explore the expression regulation mechanism of GOLPH3L. RESULTS: We demonstrated that knockdown of GOLPH3L in human breast cancer cells significantly suppressed their proliferation, survival, and migration and suppressed tumor growth in vivo, while overexpression of GOLPH3L promoted aggressive tumorigenic activities. We found that miRNA-1185-2-3p, the expression of which is decreased in human breast cancers and is inversely correlated with the prognosis of breast cancer patients, is directly involved in suppressing the expression of GOLPH3L. Metabolomics microarray analysis and transcriptome sequencing analysis revealed that GOLPH3L promotes central carbon metabolism in breast cancer by stabilizing the p53 suppressor SERPINE1. CONCLUSIONS: In summary, we discovered a miRNA-GOLPH3L-SERPINE1 pathway that plays important roles in the metabolism of breast cancer and provides new therapeutic targets for human breast cancer.
BACKGROUND:Phosphatidylinositol-4-phosphate-binding protein GOLPH3L is overexpressed in human ductal carcinoma of the breast, and its expression levels correlate with the prognosis of breast cancerpatients. However, the roles of GOLPH3L in breast tumorigenesis remain unclear. METHODS: We assessed the expression and biological function of GOLPH3L in breast cancer by combining bioinformatic prediction, metabolomics analysis and RNA-seq to determine the GOLPH3L-related pathways involved in tumorigenesis. Dual-luciferase reporter assay and coimmunoprecipitation (Co-IP) were used to explore the expression regulation mechanism of GOLPH3L. RESULTS: We demonstrated that knockdown of GOLPH3L in humanbreast cancer cells significantly suppressed their proliferation, survival, and migration and suppressed tumor growth in vivo, while overexpression of GOLPH3Lpromoted aggressive tumorigenic activities. We found that miRNA-1185-2-3p, the expression of which is decreased in human breast cancers and is inversely correlated with the prognosis of breast cancerpatients, is directly involved in suppressing the expression of GOLPH3L. Metabolomics microarray analysis and transcriptome sequencing analysis revealed that GOLPH3Lpromotes central carbon metabolism in breast cancer by stabilizing the p53 suppressor SERPINE1. CONCLUSIONS: In summary, we discovered a miRNA-GOLPH3L-SERPINE1 pathway that plays important roles in the metabolism of breast cancer and provides new therapeutic targets for humanbreast cancer.
Authors: Brock A Humphries; Johanna M Buschhaus; Yu-Chih Chen; Henry R Haley; Tonela Qyli; Benjamin Chiang; Nathan Shen; Shrila Rajendran; Alyssa Cutter; Yu-Heng Cheng; Yu-Ting Chen; Jason Cong; Phillip C Spinosa; Euisik Yoon; Kathryn E Luker; Gary D Luker Journal: Mol Cancer Res Date: 2019-02-04 Impact factor: 5.852