In:
Journal of Experimental & Clinical Cancer Research, Springer Science and Business Media LLC, Vol. 40, No. 1 ( 2021-12)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1756-9966
DOI:
10.1186/s13046-020-01767-9
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2021
detail.hit.zdb_id:
2430698-8
