MiR-128-3p suppresses breast cancer cellular progression via targeting LIMK1
Junyong Zhao1, Dengfeng Li1, Lin Fang1
1Department of Thyroid and Breast, Division of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, People's Republic of China.
Abstract:
Breast cancer is the most common malignancy in women all over the world. MiRNAs are a type of small noncoding RNA that can regulate various cellular processes via binding different target genes in cancer cells. In this study, we found that miR-128-3p could suppress cellular proliferation and motility abilities of breast cancer. In addition, we found that overexpression of miR-128-3p arrested breast cancer cells in G0/G1 phase by affecting expression of CDK4/CDK6/Cyclin D1 and CDK2/Cyclin E1. Furthermore, we confirmed that LIM domain kinase 1 (LIMK1) is a direct target gene of miR-128-3p and that overexpression of miR-128-3p could suppress the expression levels of LIMK1 and Cofilin 1, which is downstream of LIMK1. TCGA clinical database showed that miR-128-3p was highly expressed in breast cancer patients and that high expression of miR-128-3p indicates a better prognosis of breast cancer. Our findings demonstrated that miR-128-3p could regulate cellular progression of breast cancer via regulating the LIMK1/CFL1 signaling pathway, and this new avenue could broaden existing versions of molecular mechanisms in breast cancer and perhaps represent potential novel direction of breast cancer treatment in the future.
Insights
MicroRNAs (miRNAs) like miR-128-3p can suppress breast cancer growth and movement. High miR-128-3p levels in patients correlate with better breast cancer prognosis, suggesting therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Breast cancer is a leading global malignancy in women.
- MicroRNAs (miRNAs) are key regulators of cellular processes, including cancer development.
- Understanding miRNA roles offers insights into breast cancer mechanisms and treatment.
Purpose of the Study:
- To investigate the function of miR-128-3p in breast cancer.
- To identify target genes and pathways regulated by miR-128-3p.
- To explore the prognostic value of miR-128-3p in breast cancer patients.
Main Methods:
- Cell proliferation and motility assays were performed.
- Cell cycle analysis was conducted to assess effects on cell cycle regulators (CDK4/CDK6/Cyclin D1, CDK2/Cyclin E1).
- Target gene validation (LIMK1) and downstream effects (Cofilin 1) were confirmed. TCGA database analysis was used for clinical correlation.
Main Results:
- miR-128-3p significantly suppressed breast cancer cell proliferation and motility.
- Overexpression of miR-128-3p induced G0/G1 cell cycle arrest.
- LIM domain kinase 1 (LIMK1) was identified as a direct target, leading to reduced LIMK1 and Cofilin 1 expression.
- High miR-128-3p expression in patients correlated with better prognosis.
Conclusions:
- miR-128-3p acts as a tumor suppressor in breast cancer.
- The miR-128-3p/LIMK1/CFL1 pathway is crucial for regulating breast cancer progression.
- miR-128-3p represents a potential therapeutic target and biomarker for breast cancer treatment.
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