Abstract 3772: The association of androgen receptor with microRNA expression in triple-negative breast cancer

Abstract

Introduction: Triple-negative breast cancer (TNBC) is an aggressive type that lacks targeted therapies posing a challenge in its management. This necessitates identifying novel targets that may play a role in the regulation and progression of TNBC. There is renewed interest in targeting the androgen receptor (AR) since it is expressed in TNBC and plays an important role in its biology. Studies have shown that AR can influence the behavior of TNBC via affecting the of expression microRNA molecules (miRNAs), which can modulate the expression of cancer-regulatory proteins. We aimed to profile the expression of miRNAs in human TNBC tissue samples in relation to the expression of AR and investigate their prognostic value. Methods: The expression of 84 miRNAs in 24 TNBC tissue samples (12 AR-positive and 12 AR-negative) was examined using PCR array technology. Several bioinformatics tools were then utilized on the differentially expressed miRNAs (DE-miRNA) to determine the potentially affected protein targets and signaling pathways. Potential target genes (DEGs) for each miRNA were identified by miRWalk2.0. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted for the target genes using the DAVID 6.8 bioinformatics tool. String and Cytoscape were used for establishing a PPI network and identifying the hub genes. Jamovi2.2 was used for the statistical analysis. Results: A total of 7 DE-miRNAs were found to be significantly expressed in the tissue samples relative to AR expression. Good and poor survival outcomes, respectively, were found to be linked to miR-328-3p and miR-489-3p. Interestingly, these two miRNAs were found to be up-regulated in AR-positive tumors. The association of miR-328-3p with AR corroborates our previous findings that this miRNA is up-regulated upon AR activation in TNBC cells. Two other miRNAs, miR-17-5p and iR-193b-3p, were found to be significantly associated with high T3 and low N2 status, respectively. Gene Ontology (GO) analysis for the 7 DE-miRNAs indicated a role in the regulation of the cell cycle in various cellular components (CC) such as the “nucleus”, “centrosome”, and “transcription factor complex”. GO analysis also showed enrichment in kinase and transcription factor activities. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses retrieved numerous relevant signaling pathways such as that of the TGF-beta, MAPK, Th17 cell differentiation, and endocrine resistance. Conclusion: This study offers an understanding of the molecular etiology of TNBC and further implicates miRNAs in mediating the effect of AR on TNBC. We also provide an integrative analysis of the AR-miRNA-TNBC gene network that can help in identifying potential therapeutic targets. Keywords: Breast Cancer, TNBC, Bioinformatics, miRNA, Androgen Receptor Citation Format: Bayan O. Abu Alragheb, Hassan Abushukair, Maysa Al-Husseini, Randa Bawadi, Mamoun Ahram. The association of androgen receptor with microRNA expression in triple-negative breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3772.

Phosphorylation of USP27X by GSK3β maintains the stability and oncogenic functions of CBX2

“…TNBC presents a more aggressive phenotype characterized by heightened invasiveness, increased metastatic potential, greater risk of relapse, and poorer prognosis compared to other BC subtypes [ 3 ]. The development and progression of TNBC is driven by critical mutations in key signal transduction pathways including TP53, EGFR, c-KIT, VEGF, and AR that play a pivotal role in its tumorigenesis [ 4 – 8 ]. Given the aggressive nature of TNBC, identifying potential therapeutic targets is crucial for improving patient prognosis and quality of life [ 9 ].…”