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MicroRNA-563 as a potential biomarker in triple-negative breast cancer: impeding tumor progression by targeting ITGAV
Xiaobo Li1, Huiling Qin2,3, Jing Zhai4
1Department of Pathology, The Affiliated Hospital of Yanbian University (Yanbian Hospital), Yanji, Jilin, 133000, China.
Background:
Triple-negative breast cancer (TNBC) is characterized by its aggressive nature and limited treatment options, which contribute to a poor prognosis. However, the potential role of microRNA-563 (miR-563) in this malignancy remains unclear. This study investigates the tumor-suppressive role of miR-563 and its underlying mechanisms, proposing its potential as a novel biomarker in TNBC.
Methods:
The expression of miR-563 was analyzed in clinical samples of TNBC in comparison to healthy controls and non-TNBC cases. Functional assays were conducted using TNBC cell lines. Bioinformatics prediction and luciferase reporter assays identified integrin subunit alpha-V (ITGAV) as a direct target, which was further validated through rescue experiments. Additionally, epithelial-mesenchymal transition (EMT) markers were assessed to elucidate the mechanistic pathway.
Results:
MiR-563 was significantly downregulated in TNBC patients, demonstrating an area under the curve (AUC) of 0.895 for diagnosis. This downregulation correlated with advanced disease stage, lymph node metastasis, and poorer progression-free survival. Overexpression of miR-563 resulted in the suppression of TNBC cell proliferation, migration, and invasion. ITGAV was identified as a direct target of miR-563, and rescue experiments indicated a partial reversal of the tumor-suppressive effects of miR-563. Furthermore, miR-563 inhibited EMT, as evidenced by the upregulation of E-cadherin and downregulation of Vimentin.
Conclusions:
These findings identify miR-563 as a crucial tumor suppressor and a potential diagnostic predictor in TNBC, operating in part through the ITGAV-mediated pathway.
Insights
MicroRNA-563 (miR-563) acts as a tumor suppressor in triple-negative breast cancer (TNBC). Its downregulation is linked to poor prognosis, and it targets ITGAV, inhibiting cancer progression and metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Triple-negative breast cancer (TNBC) presents aggressive characteristics and limited therapeutic strategies, leading to unfavorable patient outcomes.
- The specific role of microRNA-563 (miR-563) in TNBC pathogenesis has not been well-defined.
- Investigating miR-563 offers potential for novel diagnostic and therapeutic approaches in TNBC.
Purpose of the Study:
- To elucidate the tumor-suppressive function of miR-563 in TNBC.
- To identify the molecular targets and pathways regulated by miR-563.
- To evaluate miR-563 as a potential diagnostic biomarker for TNBC.
Main Methods:
- Quantitative analysis of miR-563 expression in TNBC patient samples versus controls.
- In vitro functional assays (proliferation, migration, invasion) in TNBC cell lines with miR-563 modulation.
- Bioinformatic analysis and luciferase assays to identify and validate miR-563 targets, including ITGAV.
- Assessment of epithelial-mesenchymal transition (EMT) markers (E-cadherin, Vimentin).
Main Results:
- MiR-563 was significantly downregulated in TNBC, showing high diagnostic accuracy (AUC=0.895).
- Lower miR-563 levels correlated with advanced TNBC stage, lymph node metastasis, and reduced progression-free survival.
- Overexpressing miR-563 suppressed TNBC cell proliferation, migration, and invasion, partly via ITGAV inhibition.
- MiR-563 suppressed EMT by upregulating E-cadherin and downregulating Vimentin.
Conclusions:
- MiR-563 functions as a critical tumor suppressor in TNBC.
- MiR-563 demonstrates potential as a diagnostic predictor for TNBC.
- The tumor-suppressive effects of miR-563 are partly mediated through the ITGAV pathway, influencing EMT.
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