Related Experiment Videos
Her-2 expression regulated by downregulation of miR-9 and which affects chemotherapeutic effect in breast cancer
1Mammary Surgery Department of China-Japan Union Hospital of Jilin University, Changchun, PRC.
Abstract:
This study aimed to identify microRNAs (miRs), the deregulated expression of which leads to the activation of oncogenic pathways in human breast cancer (BC). miRs are classes of endogenous, small, noncoding RNAs that regulate gene expression aberrantly in human tumor tissues. A total of 39 out of 123 tumoral and matched uninvolved peritumoral breast specimens from 3 independent subsets of patients were analyzed for the expression of 851 human miRs using an Agilent platform. The remaining 84 samples were used to validate miRs differentially expressed between tumoral and matched peritumoral specimens by quantitative polymerase chain reaction. Animal assay was further used to test the role of miR-9 and Her-2 in the pathogenesis of BC. All 39 matched samples were analyzed by unsupervised cluster analysis. This analytical approach identified a signature of miRs (miR-9, miR-148a, miR-31, miR-375, miR-21, miR-135b, miR-196a and miR-196b) that were significantly modulated between tumoral and peritumoral tissues in both subsets of patients. Her-2 protein staining increased in tumoral specimens when miR-9 downregulation correlated with the prognostic value. The ectopic expression of miR-9 inhibited the colony-forming ability, migration and tumor engraftment of BC cells. miR-9 targeted the Her-2 messenger RNA and increased responsiveness of BC cells to docetaxel (DOC) or cyclophosphamide treatment. The ectopic expression of Her-2 protein counteracted the miR-9 proapoptotic activity in response to DOC. These findings suggested that the modulation of aberrant expression of miR-9, which in turn induces oncogenic Her-2 protein activity, might hold promise for preventive and therapeutic management of BC.
Insights
This study identified a microRNA signature, including miR-9, involved in breast cancer pathogenesis. Downregulation of miR-9 correlates with Her-2 activity and impacts treatment response, suggesting therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRs) are small, noncoding RNAs that regulate gene expression and are often aberrantly expressed in human cancers.
- Deregulation of miRs can activate oncogenic pathways, contributing to the development and progression of human breast cancer (BC).
Purpose of the Study:
- To identify specific microRNAs (miRs) with deregulated expression in human breast cancer (BC).
- To investigate the role of miR-9 and Her-2 in BC pathogenesis and their potential as therapeutic targets.
Main Methods:
- Expression profiling of 851 miRs in tumoral and peritumoral breast tissues using an Agilent platform.
- Validation of differentially expressed miRs via quantitative polymerase chain reaction and unsupervised cluster analysis.
- In vivo animal assays to assess the functional roles of miR-9 and Her-2 in BC.
Main Results:
- A distinct miR signature (miR-9, miR-148a, miR-31, miR-375, miR-21, miR-135b, miR-196a, miR-196b) was identified, significantly modulated in tumoral versus peritumoral tissues.
- Downregulation of miR-9 correlated with increased Her-2 protein expression and had prognostic value.
- Ectopic miR-9 expression inhibited BC cell proliferation, migration, and tumor engraftment, and enhanced sensitivity to chemotherapy.
Conclusions:
- Aberrant miR-9 expression, linked to oncogenic Her-2 activity, plays a crucial role in breast cancer development.
- Modulating miR-9 offers potential for novel preventive and therapeutic strategies in breast cancer management.