Dataset Information

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 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.

SUBMITTER: Xu Y

PROVIDER: S-EPMC7842049 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Xu Youqin Y Chen Wancheng W Liang Jing J Zeng Xiaoqi X Ji Kaiyuan K Zhou Jianlong J Liao Shijun S Wu Jiexian J Xing Kongyang K He Zilong Z Yang Yang Y Liu Qianzhen Q Zhu Pingyi P Liu Yuchang Y Li Li L Liu Minfeng M Chen Wenxiao W Huang Wenhua W

Journal of experimental & clinical cancer research : CR 20210128 1

<h4>Background</h4>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.<h4>Methods</h4>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 invol ...[more]

PMID: 33509226

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Project description:BackgroundCircular RNAs (circRNAs) participate in the development of atherosclerotic cardiovascular disease. Identifying and verifying the key competing endogenous RNA (ceRNA) network related to atherosclerosis (AS) is significant for understanding the development of AS. The aim of this study was to investigate the circRNA-miRNA‒mRNA network, identify a key circRNA and explore its role in the development of atherosclerosis.MethodsDifferentially expressed mRNAs (DEMs) and circRNAs (DECs) in the AS model were obtained from datasets in the Gene Expression Omnibus (GEO) database. R software and Cytoscape software were used to construct and visualize the ceRNA network. The dual-luciferase reporter experiment and the RNA pull-down experiment were used to verify the selected ceRNA axis. siRNA targeting circRNA, miRNA mimic, miRNA inhibitor, or gene overexpression plasmid was used for in vitro functional studies. ELISA and western blotting were used to detect inflammation and lipid transport-related proteins. Furthermore, an AS mouse model was established and treated with recombinant adeno-associated viral vectors to further verify the influence of the selected ceRNA axis on the occurrence and/or development of AS.ResultsA total of 497 DEMs were enriched in 25 pathways, based on which the circ_0082139 (circSnd1)/miR-485-3p/Olr1 axis was selected. In vitro, the interaction among the three molecules of this axis was validated and it was found to affect inflammation and lipid transport, which were characterized by the significant change of inflammatory factors (Il-6, Il-8, Tnf-α, Mcp-1, Vcam-1, and Icam-1), and lipid transport-related genes, including Abca1, Abcg1, Ldlr, Hdlbp, Lp-pla2, and Srebp-1c. Through animal experiments, we further verified that the circSnd1/miR-485-3p/Olr1 axis regulated these molecules and participated in the formation and/or development of AS in vivo.ConclusionsThe circSnd1/miR-485-3p/Olr1 axis participates in the formation and development of atherosclerosis by regulating inflammation and lipid transport.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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