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MiR-491 suppresses migration and invasion via directly targeting TPX2 in breast cancer
1Department of Oncology, Jinan City People's Hospital, Jinan, China. tgz964@sina.com.
Objective:
Breast cancer (BC) is one of the primary causes of tumor-related female mortalities. Although in recent years, we have made great progress in the systemic therapy and earlier diagnosis for BC patients, recurrence or distant metastasis remains leading obstacles for the successful therapy of BC. Therefore, a comprehensive understanding of the molecular mechanism underlying the progression may be crucial in developing an effective strategy against BC. The current research aimed to explore the expressions, functions and molecular mechanism of microRNA-491 (miR-491) in BC.
Patients And Methods:
Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the level of miR-491 expression in 52 pairs of BC tissues and para-cancerous specimens, and the relation between miR-491 level and the clinical features of BC patient prognosis was analyzed. Transwell invasion and migration assays were conducted to determine whether miR-491 had effects on the regulation of BC metastasis. Potential target genes of miR-491 were found out using TargetScan to explore the molecular functions of miR-491 in inhibiting breast cancer cell invasion and migration. To elucidate the mechanism of TPX2 in suppressing cell invasion and migration medicated by miR-491in breast cancer, we further transfected TPX2 siRNAs into MCF-7 cells to delete endogenous TPX2, along with the transfections with miR-491 inhibitor into MCF-7 cell lines.
Results:
The findings demonstrated that miR-491 expressions were significantly decreased in BC tissues and cells. The miR-491 restoration suppressed the invasion and migration of BC cells. In addition, we identified the targeting protein for Xklp2 (TPX2) as a direct target of miR-491 in BC. The knockdown of TPX2 markedly reversed miR-491-medicated inhibition of cell invasion and migration in BC cell lines.
Conclusions:
In short, all the results suggested that miR-491 functioned as a tumor suppressor by targeting TPX2 in BC and the miR-491 restoration may be an effective therapy for the BC treatment in the future.
Insights
MicroRNA-491 (miR-491) is decreased in breast cancer (BC) and acts as a tumor suppressor. Restoring miR-491 inhibits BC cell invasion and migration by targeting TPX2, suggesting a potential therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Breast cancer (BC) remains a leading cause of cancer mortality in women globally.
- Despite advances in diagnosis and therapy, tumor recurrence and distant metastasis present significant challenges in BC treatment.
- Understanding the molecular mechanisms driving BC progression is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To investigate the expression levels of microRNA-491 (miR-491) in breast cancer tissues and cells.
- To elucidate the functional role of miR-491 in regulating BC cell invasion and migration.
- To identify the molecular targets and mechanisms through which miR-491 exerts its effects in BC.
Main Methods:
- Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) was used to measure miR-491 expression in 52 BC tissue/para-cancerous specimen pairs.
- Transwell assays were performed to assess the impact of miR-491 on BC cell invasion and migration.
- Bioinformatic analysis (TargetScan) identified potential miR-491 targets, followed by functional validation using siRNA-mediated knockdown of TPX2 in BC cell lines.
Main Results:
- miR-491 expression was significantly downregulated in breast cancer tissues and cells compared to normal controls.
- Restoration of miR-491 expression suppressed the invasion and migration capabilities of BC cells.
- Targeting protein for Xklp2 (TPX2) was identified as a direct target of miR-491, and its knockdown reversed the anti-metastatic effects of miR-491.
Conclusions:
- miR-491 functions as a tumor suppressor in breast cancer by directly targeting TPX2.
- The findings suggest that miR-491 restoration holds promise as a potential therapeutic approach for breast cancer treatment.