机构：[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深圳市中医院深圳医学信息中心[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深圳医学信息中心中国医学科学院阜外医院深圳医院[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.
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.
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.
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.
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.
基金：
This study is supported by the National Natural Science Foundation of China
(Grant No. 81902865 and Grant No. 61427807), the China Postdoctoral
Science Foundation (2019 M652974), Sanming Project of Medicine in
Shenzhen (SZSM201612019), the Science and Technology Foundation of
Jiangmen (JK [2020] No. 58-2020YLI010), the Medical Science and Technology Research Foundation of Guangdong Province (YWJKH [2020] No. 15-
A2020510), and the President’s Fund of Nanfang Hospital, Southern Medical
University (Grant No. 2019C017)
第一作者机构：[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.
共同第一作者：
通讯作者：
通讯机构：[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.[8]Department of Pathology, School of Basic Medicine, Guangdong Medical University, Zhanjiang 524023, China.
推荐引用方式(GB/T 7714)：
Xu Youqin,Chen Wancheng,Liang Jing,et al.The miR-1185-2-3p-GOLPH3L pathway promotes glucose metabolism in breast cancer by stabilizing p53-induced SERPINE1.[J].JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH.2021,40(1):doi:10.1186/s13046-020-01767-9.
APA：
Xu Youqin,Chen Wancheng,Liang Jing,Zeng Xiaoqi,Ji Kaiyuan...&Huang Wenhua.(2021).The miR-1185-2-3p-GOLPH3L pathway promotes glucose metabolism in breast cancer by stabilizing p53-induced SERPINE1..JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,40,(1)
MLA：
Xu Youqin,et al."The miR-1185-2-3p-GOLPH3L pathway promotes glucose metabolism in breast cancer by stabilizing p53-induced SERPINE1.".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 40..1(2021)
医学