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Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
Bioinformatic identification of chemoresistance-associated microRNAs in breast cancer based on microarray data
Ya-Wen Wang1, Weiguo Zhang1, Rong Ma1
1Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Abstract:
Breast cancer is the most commonly diagnosed cancer among females, and chemoresistance constitutes a major clinical obstacle to the treatment of this disease. MicroRNAs (miRNAs) are related to human cancer development, progression and drug resistance. To identify breast cancer chemoresistance-associated miRNAs, miRNA microarray dataset GSE71142, including five chemoresistant breast cancer tissues and five chemosensitive tissues, was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DE-miRNAs) were obtained by t-test and the potential target genes were predicted by miRWalk2.0. Functional and pathway enrichment analysis by WebGestalt was performed for the potential target genes of DE-miRNAs. Protein-protein interaction (PPI) network was established by STRING database and visualized by Cytoscape software. Enriched transcription factors by the target genes were obtained from FunRich. Breast cancer-associated miRNA‑gene pairs were identified from miRWalk2.0. A total of 22 DE-miRNAs were screened out, including 10 upregulated miRNAs (e.g., miR-196a-5p) and 12 downregulated miRNAs (e.g., miR-4472) in the chemoresistant breast cancer tissues, compared with chemosensitive tissues. In total 1,278 target genes were screened out, and they were involved in breast cancer-related pathways such as pathways in cancer, signaling pathways regulating pluripotency of stem cells, endocrine resistance, breast cancer, mTOR signaling and Hippo signaling pathway. NOTCH1 and MAPK14 were identified as hub genes in the PPI network. EGR1 and SP1 were the most enriched transcription factors by the target genes. Several breast cancer-associated miRNA-gene pairs including miR-214-TP53 and miR-16-PPM1D were identified. The current bioinformatics study of miRNAs based on microarray may offer a new understanding into the mechanisms of breast cancer chemoresistance, and may identify novel miRNA therapeutic targets.
Insights
This study identifies key microRNAs (miRNAs) and their target genes associated with chemoresistance in breast cancer. Findings may lead to new therapeutic targets for improving breast cancer treatment outcomes.
Area of Science:
- Oncology
- Genetics
- Bioinformatics
Background:
- Breast cancer is a prevalent disease in females, with chemoresistance posing a significant treatment challenge.
- MicroRNAs (miRNAs) play a crucial role in cancer development, progression, and drug resistance.
Purpose of the Study:
- To identify microRNAs (miRNAs) associated with chemoresistance in breast cancer.
- To explore the functional roles and pathways of differentially expressed miRNAs (DE-miRNAs) and their target genes.
Main Methods:
- Downloaded and analyzed miRNA microarray dataset GSE71142 from the Gene Expression Omnibus (GEO) database.
- Identified DE-miRNAs using t-test, predicted target genes with miRWalk2.0, and performed functional enrichment analysis with WebGestalt.
- Constructed a protein-protein interaction (PPI) network using STRING and visualized it with Cytoscape.
Main Results:
- Identified 22 DE-miRNAs (10 upregulated, 12 downregulated) in chemoresistant versus chemosensitive breast cancer tissues.
- Screened 1,278 target genes involved in critical cancer pathways, including endocrine resistance and mTOR signaling.
- Identified NOTCH1 and MAPK14 as hub genes, EGR1 and SP1 as enriched transcription factors, and several miRNA-gene pairs like miR-214-TP53.
Conclusions:
- This bioinformatics study provides insights into the molecular mechanisms of breast cancer chemoresistance.
- Identified potential novel miRNA therapeutic targets for overcoming chemoresistance in breast cancer treatment.
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