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Expression of Dicer and Drosha in triple-negative breast cancer
Nadia Passon1, Anna Gerometta, Cinzia Puppin
1Dipartimento di Scienze Mediche e Biologiche, Università di Udine, Udine, Italy.
Aims:
Dicer and Drosha are components of the miRNA-producing machinery and their altered expression may play a role in cancer progression. The main purpose of this study was a detailed investigation of Dicer and Drosha expression and localisation in triple-negative breast cancers.
Methods:
Thirty-one triple-negative breast cancers and several breast cancer cell lines were investigated. Expression of Dicer and Drosha was evaluated at the mRNA level by quantitative reverse transcription PCR and at the protein level by immunohistochemistry or western blot.
Results:
Compared with normal breast tissues, a wide variation of Dicer and Drosha mRNA levels was detected in triple-negative breast cancers. As a group, Drosha mRNA levels in triple-negative breast cancers were significantly higher than those in normal breast tissues. Immunohistochemical data confirmed higher expression of Drosha protein in triple-negative breast cancers. In normal breast tissues Dicer was detectable predominantly in the cytoplasm of basal/myoepithelial cells only. In contrast, in the majority of triple-negative breast cancers, intense Dicer staining was detectable also in the nuclear compartment. Detection of Dicer and Drosha mRNA and protein levels in breast cancer cell lines confirmed the nuclear localisation of Dicer, suggesting, in addition, that the steady-state protein levels could be controlled by post-mRNA regulatory events.
Conclusions:
These findings indicate that Dicer and Drosha expression is deregulated in triple-negative breast cancers.
Insights
Dicer and Drosha expression is altered in triple-negative breast cancers (TNBC). This study found deregulated Dicer and Drosha levels and altered Dicer localization in TNBC tissues and cell lines.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Dicer and Drosha are key enzymes in microRNA (miRNA) biogenesis.
- Aberrant miRNA machinery component expression is implicated in cancer development and progression.
Purpose of the Study:
- To investigate the expression and localization patterns of Dicer and Drosha in triple-negative breast cancers (TNBC).
- To compare Dicer and Drosha expression in TNBC with normal breast tissues.
Main Methods:
- Quantitative reverse transcription PCR (qRT-PCR) for mRNA analysis.
- Immunohistochemistry and Western blot for protein expression and localization.
- Analysis of 31 TNBC samples and breast cancer cell lines.
Main Results:
- Dicer and Drosha mRNA levels showed significant variation in TNBC compared to normal tissues, with Drosha mRNA levels being significantly higher overall.
- Drosha protein expression was also elevated in TNBC.
- Dicer protein, typically cytoplasmic in normal breast tissue, showed significant nuclear localization in the majority of TNBC samples.
Conclusions:
- Dicer and Drosha expression and localization are deregulated in triple-negative breast cancers.
- These findings highlight potential roles for Dicer and Drosha in TNBC pathogenesis.
