The miR-1185-2-3p—GOLPH3L pathway promotes glucose metabolism in breast cancer by stabilizing p53-induced SERPINE1
| Autor: | Kaiyuan Ji, Jiexian Wu, Wenxiao Chen, Youqin Xu, Yuchang Liu, Kongyang Xing, Pingyi Zhu, Yang Yang, Jing Liang, Qianzhen Liu, Zilong He, Shijun Liao, Wenhua Huang, Li Li, Minfeng Liu, Jianlong Zhou, Wancheng Chen, Xiaoqi Zeng |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Glycosylation p53-induced transcription Breast Neoplasms Biology medicine.disease_cause lcsh:RC254-282 Mice Breast cancer Genes Reporter Cell Line Tumor microRNA Plasminogen Activator Inhibitor 1 medicine Animals Humans Metabolomics skin and connective tissue diseases miRNA Gene knockdown Glucose metabolism Microarray analysis techniques Research Cancer Computational Biology Ductal carcinoma lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Phosphoproteins Prognosis Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic Disease Models Animal MicroRNAs Cell Transformation Neoplastic Glucose Oncology Cancer cell Tumorigenesis Cancer research Female Tumor Suppressor Protein p53 Carcinogenesis Signal Transduction |
| Zdroj: | Journal of Experimental & Clinical Cancer Research : CR Journal of Experimental & Clinical Cancer Research, Vol 40, Iss 1, Pp 1-20 (2021) |
| ISSN: | 1756-9966 0392-9078 |
| Popis: | BackgroundPhosphatidylinositol-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.MethodsWe 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.ResultsWe 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.ConclusionsIn 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. |
| Databáze: | OpenAIRE |
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