The miR-1185-2-3p-GOLPH3L pathway promotes glucose metabolism in breast cancer by stabilizing p53-induced SERPINE1

• Published in: Journal of experimental & clinical cancer research 2021-01, Vol.40 (1), p.47-47, Article 47
• Main Authors: Xu, Youqin, Chen, Wancheng, Liang, Jing, Zeng, Xiaoqi, Ji, Kaiyuan, Zhou, Jianlong, Liao, Shijun, Wu, Jiexian, Xing, Kongyang, He, Zilong, Yang, Yang, Liu, Qianzhen, Zhu, Pingyi, Liu, Yuchang, Li, Li, Liu, Minfeng, Chen, Wenxiao, Huang, Wenhua
• Format: Article
• Language: English
• Subjects: Analysis; Apoptosis; Biosynthesis; Breast cancer; Cell cycle; Cell growth; Dextrose; DNA microarrays; Genomes; Glucose; Glucose metabolism; Glycosylation; Metabolism; Metabolites; Metastasis; MicroRNAs; miRNA; p53-induced transcription; Phosphates; Phosphorylation; Physiological aspects; Prognosis; Protein binding; Proteins; RNA; Signal transduction; Tumor proteins; Tumorigenesis; Tumors
• ISSN: 1756-9966; 0392-9078; 1756-9966
• DOI: 10.1186/s13046-020-01767-9

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.