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作者

Youqin Xu Wancheng Chen Jing Liang Xiaoqi Zeng Kaiyuan Ji Jianlong Zhou Shijun Liao Jiexian Wu Kongyang Xing Zilong He Yang Yang Qianzhen Liu Pingyi Zhu Yuchang Liu Li Li Minfeng Liu Wenxiao Chen Wenhua Huang

作者单位

Taishan People’s Hospital, Postdoctoral Innovation Practice Base of Southern Medical University National Key Discipline of Human Anatomy, School of Basic Medical Science, Southern Medical University School of Basic Medical Science, Guangzhou University of Chinese Medicine Breast Center, Department of general surgery, Nanfang Hospital, Southern Medical University The Eighth Affiliated Hospital, Sun Yat-sen University National Key Discipline of Human Anatomy, School of Basic Medical Science, Southern Medical University Breast Center, Department of general surgery, Nanfang Hospital, Southern Medical University Taishan People’s Hospital, Postdoctoral Innovation Practice Base of Southern Medical University Taishan People’s Hospital, Postdoctoral Innovation Practice Base of Southern Medical University Department of Radiology, Nanfang Hospital, Southern Medical University National Key Discipline of Human Anatomy, School of Basic Medical Science, Southern Medical University Department of Pathology, School of Basic Medicine, Guangdong Medical University Taishan People’s Hospital, Postdoctoral Innovation Practice Base of Southern Medical University Taishan People’s Hospital, Postdoctoral Innovation Practice Base of Southern Medical University Taishan People’s Hospital, Postdoctoral Innovation Practice Base of Southern Medical University Breast Center, Department of general surgery, Nanfang Hospital, Southern Medical University Taishan People’s Hospital, Postdoctoral Innovation Practice Base of Southern Medical University Taishan People’s Hospital, Postdoctoral Innovation Practice Base of Southern Medical University

刊名

Journal of Experimental & Clinical Cancer Research

年份

2021

卷号

Vol.40 No.1

页码

1-20

ISSN

1756-9966

关键词

Tumorigenesis Glucose metabolism Glycosylation miRNA p53-induced transcription

摘要

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 tumorige...更多

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 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.收起

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