The miR-1185-2-3p—GOLPH3L pathway promotes glucose metabolism in breast cancer by stabilizing p53-induced SERPINE1
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 as...
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doaj-0a9c497b61da4fbdb4ffea8645da3be52021-01-31T12:10:58ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662021-01-0140112010.1186/s13046-020-01767-9The miR-1185-2-3p—GOLPH3L pathway promotes glucose metabolism in breast cancer by stabilizing p53-induced SERPINE1Youqin Xu0Wancheng Chen1Jing Liang2Xiaoqi Zeng3Kaiyuan Ji4Jianlong Zhou5Shijun Liao6Jiexian Wu7Kongyang Xing8Zilong He9Yang Yang10Qianzhen Liu11Pingyi Zhu12Yuchang Liu13Li Li14Minfeng Liu15Wenxiao Chen16Wenhua Huang17Taishan People’s Hospital, Postdoctoral Innovation Practice Base of Southern Medical UniversityNational Key Discipline of Human Anatomy, School of Basic Medical Science, Southern Medical UniversitySchool of Basic Medical Science, Guangzhou University of Chinese MedicineBreast Center, Department of general surgery, Nanfang Hospital, Southern Medical UniversityThe Eighth Affiliated Hospital, Sun Yat-sen UniversityNational Key Discipline of Human Anatomy, School of Basic Medical Science, Southern Medical UniversityBreast Center, Department of general surgery, Nanfang Hospital, Southern Medical UniversityTaishan People’s Hospital, Postdoctoral Innovation Practice Base of Southern Medical UniversityTaishan People’s Hospital, Postdoctoral Innovation Practice Base of Southern Medical UniversityDepartment of Radiology, Nanfang Hospital, Southern Medical UniversityNational Key Discipline of Human Anatomy, School of Basic Medical Science, Southern Medical UniversityDepartment of Pathology, School of Basic Medicine, Guangdong Medical UniversityTaishan People’s Hospital, Postdoctoral Innovation Practice Base of Southern Medical UniversityTaishan People’s Hospital, Postdoctoral Innovation Practice Base of Southern Medical UniversityTaishan People’s Hospital, Postdoctoral Innovation Practice Base of Southern Medical UniversityBreast Center, Department of general surgery, Nanfang Hospital, Southern Medical UniversityTaishan People’s Hospital, Postdoctoral Innovation Practice Base of Southern Medical UniversityTaishan People’s Hospital, Postdoctoral Innovation Practice Base of Southern Medical UniversityAbstract 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.https://doi.org/10.1186/s13046-020-01767-9TumorigenesisGlucose metabolismGlycosylationmiRNAp53-induced transcription |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 The miR-1185-2-3p—GOLPH3L pathway promotes glucose metabolism in breast cancer by stabilizing p53-induced SERPINE1 Journal of Experimental & Clinical Cancer Research Tumorigenesis Glucose metabolism Glycosylation miRNA p53-induced transcription |
author_facet |
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 |
author_sort |
Youqin Xu |
title |
The miR-1185-2-3p—GOLPH3L pathway promotes glucose metabolism in breast cancer by stabilizing p53-induced SERPINE1 |
title_short |
The miR-1185-2-3p—GOLPH3L pathway promotes glucose metabolism in breast cancer by stabilizing p53-induced SERPINE1 |
title_full |
The miR-1185-2-3p—GOLPH3L pathway promotes glucose metabolism in breast cancer by stabilizing p53-induced SERPINE1 |
title_fullStr |
The miR-1185-2-3p—GOLPH3L pathway promotes glucose metabolism in breast cancer by stabilizing p53-induced SERPINE1 |
title_full_unstemmed |
The miR-1185-2-3p—GOLPH3L pathway promotes glucose metabolism in breast cancer by stabilizing p53-induced SERPINE1 |
title_sort |
mir-1185-2-3p—golph3l pathway promotes glucose metabolism in breast cancer by stabilizing p53-induced serpine1 |
publisher |
BMC |
series |
Journal of Experimental & Clinical Cancer Research |
issn |
1756-9966 |
publishDate |
2021-01-01 |
description |
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. |
topic |
Tumorigenesis Glucose metabolism Glycosylation miRNA p53-induced transcription |
url |
https://doi.org/10.1186/s13046-020-01767-9 |
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