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miR-335-5p Targets SDC1 to Regulate the Progression of Breast Cancer
Guoqing Song1, Yao Ma1, Yinghan Ma1
1Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Abstract:
The objective of the study was to explore the role of SDC1 in breast cancer cells. Our study also investigated the regulatory relationship between SDC1 and the microRNA (miRNA) miR-335-5p as well as the impact of these two genes on the progression of breast cancer. Bioinformatic approaches were employed to analyze the differentially expressed messenger RNAs (mRNAs) and miRNAs (DE-mRNAs and DE-miRNAs) in breast cancer tissue. Then mRNA SC1 was obtained. Differentially downregulated mRNAs were intersected with target miRNAs predicted by databases, and miR-335-5p was determined as the study object. Quantitative reverse transcription polymerase chain reaction was applied to assess the expressions of SDC1 and miR-335-5p in each cell line. Next, Western blot assay was conducted to detect the protein level of SDC1 and dual-luciferase assay was performed to verify the binding relationship between miR-335-5p and SDC1. Finally, we conducted methyl thiazolyl tetrazolium (MTT), colony formation, and Transwell assays and flow cytometry to further investigate the impacts of SDC1 and miR-335-5p on the progression of breast cancer. SDC1 was significantly highly expressed while miR-335-5p was remarkably lowly expressed in human breast cancer. Silencing SDC1 in breast cancer blocked the proliferation, migration and invasion of the cells. In breast cancer, SDC1 was a target gene of miR-335-5p and silencing miR-335-5p notably increased SDC1 expression. Compared with the silence of miR-335-5p, simultaneous silences of miR-335-5p and SDC1 significantly reduced the proliferative, migratory and invasive abilities of breast cancer cells. The result revealed the interaction between miR-335-5p and SDC1 in the progression of breast cancer, which may contribute to the treatments for this cancer.
Insights
This study reveals Syndecan-1 (SDC1) is highly expressed and promotes breast cancer progression. Its downregulation, alongside increased microRNA (miRNA) miR-335-5p, inhibits cancer cell proliferation, migration, and invasion.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Breast cancer is a significant global health concern with complex molecular underpinnings.
- Understanding the roles of specific genes and microRNAs is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of Syndecan-1 (SDC1) in breast cancer progression.
- To explore the regulatory relationship between SDC1 and microRNA (miRNA) miR-335-5p.
- To assess the combined impact of SDC1 and miR-335-5p on breast cancer development.
Main Methods:
- Bioinformatic analysis of differentially expressed genes and miRNAs in breast cancer tissues.
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) for gene expression analysis.
- Western blot, dual-luciferase assay, MTT, colony formation, Transwell, and flow cytometry assays to evaluate gene function and interactions.
Main Results:
- SDC1 was significantly upregulated, while miR-335-5p was downregulated in human breast cancer.
- Silencing SDC1 inhibited breast cancer cell proliferation, migration, and invasion.
- SDC1 was identified as a direct target of miR-335-5p, with miR-335-5p silencing increasing SDC1 expression.
- Simultaneous silencing of both miR-335-5p and SDC1 markedly reduced cancer cell abilities.
Conclusions:
- The study elucidates a critical interaction between miR-335-5p and SDC1 in breast cancer progression.
- This regulatory axis presents a potential therapeutic target for breast cancer treatment.
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