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Updated: Jul 2, 2025

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
MicroRNA-203a inhibits breast cancer progression through the PI3K/Akt and Wnt pathways
Maryam Entezari1, Bahram M Soltani1, Majid Sadeghizadeh2
1Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, 14115-111, Iran.
Abstract:
MicroRNA expression in breast cancer (BC) is explored both as a potential biomarker and for therapeutic purposes. Recent studies have revealed that miR-203a-3p is involved in BC, and importantly contributes to BC chemotherapy responses; however, the regulatory pathways of miR-203a in BC remain elusive. Hence, we aimed to investigate the miR-203a regulatory mechanisms and their potential functions in the progress of BC. To this end, the miR-203a potential involving pathways was predicted by databases analyzing its target genes. The relations between miR-203a, the phosphatidylinositol 3'-kinase (PI3K)-Akt, and Wnt signaling pathways were mechanistically investigated. Our results revealed that miR-203a inhibited the activation of the PI3K/Akt and Wnt pathways and reduced its downstream cell cycle signals, including Cyclin D1 and c-Myc. Moreover, the overexpression of miR-203a drastically arrested the cell cycle at subG1 and G1 phases, decreased the viability, proliferation, and migration, and increased apoptosis of BC cells. Therefore, miR-203a-3p may be considered a tumor suppressor factor and a potential biomarker or therapeutic target for BC.
Insights
MicroRNA miR-203a-3p acts as a tumor suppressor in breast cancer (BC) by inhibiting key signaling pathways. This finding suggests miR-203a-3p is a potential biomarker and therapeutic target for BC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA (miRNA) expression is crucial in breast cancer (BC) for biomarker and therapeutic development.
- miR-203a-3p's role in BC and its contribution to chemotherapy response are recognized, but its regulatory mechanisms remain unclear.
- Understanding miR-203a's regulatory pathways is essential for advancing BC treatment strategies.
Purpose of the Study:
- To elucidate the regulatory mechanisms of miR-203a in breast cancer progression.
- To investigate the functional roles of miR-203a in BC.
- To explore the relationship between miR-203a and critical signaling pathways in BC.
Main Methods:
- Bioinformatic prediction of miR-203a target genes and associated pathways.
- Mechanistic investigation of miR-203a interactions with phosphatidylinositol 3'-kinase (PI3K)-Akt and Wnt signaling pathways.
- Assessment of miR-203a's effects on cell cycle, viability, proliferation, migration, and apoptosis in BC cells.
Main Results:
- miR-203a was found to inhibit the activation of PI3K/Akt and Wnt signaling pathways.
- miR-203a suppressed downstream cell cycle regulators, including Cyclin D1 and c-Myc.
- Overexpression of miR-203a led to cell cycle arrest (subG1 and G1 phases), reduced viability, proliferation, and migration, and increased apoptosis in BC cells.
Conclusions:
- miR-203a-3p functions as a tumor suppressor in breast cancer.
- miR-203a-3p demonstrates potential as a diagnostic biomarker for BC.
- miR-203a-3p represents a promising therapeutic target for breast cancer treatment.
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