miRNome and Functional Network Analysis of PGRMC1 Regulated miRNA Target Genes Identify Pathways and Biological Functions Associated With Triple Negative Breast Cancer
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Updated: Oct 25, 2025
Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
Diego A Pedroza1, Matthew Ramirez1, Venkatesh Rajamanickam2
1Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United States.
Background:
Increased expression of the progesterone receptor membrane component 1, a heme and progesterone binding protein, is frequently found in triple negative breast cancer tissue. The basis for the expression of PGRMC1 and its regulation on cellular signaling mechanisms remain largely unknown. Therefore, we aim to study microRNAs that target selective genes and mechanisms that are regulated by PGRMC1 in TNBCs.
Methods:
To identify altered miRNAs, whole human miRNome profiling was performed following AG-205 treatment and PGRMC1 silencing. Network analysis identified miRNA target genes while KEGG, REACTOME and Gene ontology were used to explore altered signaling pathways, biological processes, and molecular functions.
Results:
KEGG term pathway analysis revealed that upregulated miRNAs target specific genes that are involved in signaling pathways that play a major role in carcinogenesis. While multiple downregulated miRNAs are known oncogenes and have been previously demonstrated to be overexpressed in a variety of cancers. Overlapping miRNA target genes associated with KEGG term pathways were identified and overexpression/amplification of these genes was observed in invasive breast carcinoma tissue from TCGA. Further, the top two genes (CCND1 and YWHAZ) which are highly genetically altered are also associated with poorer overall survival.
Conclusions:
Thus, our data demonstrates that therapeutic targeting of PGRMC1 in aggressive breast cancers leads to the activation of miRNAs that target overexpressed genes and deactivation of miRNAs that have oncogenic potential.
Insights
Targeting progesterone receptor membrane component 1 (PGRMC1) in triple-negative breast cancer activates microRNAs. These microRNAs target overexpressed genes and deactivate oncogenic miRNAs, offering a new therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Progesterone receptor membrane component 1 (PGRMC1) is upregulated in triple-negative breast cancer (TNBC).
- The regulatory mechanisms and signaling pathways influenced by PGRMC1 in TNBC are not well understood.
- MicroRNAs (miRNAs) are key regulators of gene expression and are implicated in cancer development.
Purpose of the Study:
- To investigate the role of microRNAs (miRNAs) in regulating genes and signaling pathways controlled by PGRMC1 in TNBC.
- To identify specific miRNAs that are altered in response to PGRMC1 modulation.
- To explore the therapeutic potential of targeting PGRMC1 in aggressive breast cancers.
Main Methods:
- Whole human miRNome profiling was conducted after AG-205 treatment and PGRMC1 silencing.
- Network analysis was employed to identify miRNA target genes.
- Pathway analysis using KEGG, REACTOME, and Gene Ontology was performed to explore altered signaling.
Main Results:
- Upregulated miRNAs were found to target genes involved in carcinogenesis signaling pathways.
- Downregulated miRNAs included known oncogenes previously implicated in various cancers.
- Overexpression/amplification of overlapping miRNA target genes was observed in invasive breast carcinoma patient data (TCGA).
- The genes CCND1 and YWHAZ, highly genetically altered, were associated with poorer overall survival.
Conclusions:
- Therapeutic targeting of PGRMC1 in aggressive breast cancers activates miRNAs.
- These activated miRNAs target genes that are overexpressed in cancer.
- The approach also leads to the deactivation of miRNAs with oncogenic potential.
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