MicroRNAome profiling of breast cancer unveils hsa-miR-5683 as a tumor suppressor microRNA predicting favorable clinical outcome
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View abstract on PubMed
Summary
This summary is machine-generated.This study reveals microRNA (miRNA) expression patterns across breast cancer subtypes. hsa-miR-5683 shows promise as a prognostic biomarker and therapeutic target, particularly in triple-negative breast cancer (TNBC).
Area Of Science
- Genomics and Molecular Biology
- Cancer Research
- Biomarker Discovery
Background
- Breast cancer is a complex disease with diverse molecular subtypes requiring novel prognostic biomarkers and therapeutic targets.
- Understanding molecular features and regulatory mechanisms is crucial for improving breast cancer patient care.
Purpose Of The Study
- To profile microRNA (miRNA) expression across breast cancer subtypes.
- To identify novel miRNA biomarkers and therapeutic targets for breast cancer.
- To elucidate the role of specific miRNAs, such as hsa-miR-5683, in breast cancer progression and tumorigenicity.
Main Methods
- miRNAome profiling of 96 FFPE breast cancer samples using QIAseq miRNA library kit and Illumina sequencing.
- Mature miRNA quantification and Relapse-free Survival (RFS) analysis.
- Gain-of-function studies with miRNA mimics, 2D/3D cell culture assays, and miRNA target identification using TargetScan and IPA.
Main Results
- Hierarchical clustering identified distinct miRNA expression patterns associated with PAM50 subtypes (luminal, HER2, basal).
- hsa-miR-5683 demonstrated prognostic value, correlating with RFS and suppressing tumorigenicity in triple-negative breast cancer (TNBC) and hormone receptor-positive (HR+) models.
- Transcriptomic profiling and CRISPR-Cas9 analysis identified key gene targets of hsa-miR-5683, including ACLY, RACGAP1, and SOD1, involved in oncogenic pathways.
Conclusions
- A comprehensive miRNA expression atlas for breast cancer subtypes was generated.
- hsa-miR-5683 is highlighted as a significant prognostic and therapeutic target, especially for TNBC.
- Identified gene targets provide insights into TNBC regulatory networks, suggesting potential for targeted therapies.
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