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Published on: June 9, 2023
miR-641 Inhibited Cell Proliferation and Induced Apoptosis by Targeting NUCKS1/PI3K/AKT Signaling Pathway in Breast
Li Li1,2, Da Wei1,2, Junying Zhang1,3
1Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing 210009, China.
Objective:
Studies revealed an important role of microRNAs (miRNAs) in multiple cancers, including breast cancer. In the present study, we evaluated the role and function of miR-641 in breast cancer.
Methods:
The expression level of miR-641 in breast cancer cell lines (Hs-578T, MCF7, HCC1937, and MAD-MB-231) was determined by real-time PCR. Functional analyses, including CCK-8 assay, transwell assay, wound-healing assay, and apoptosis detection, were carried out to explore the roles of miRNA-641 in malignant behaviors of breast cancer. Luciferase report assay was used to investigate the regulatory association of miRNA-641 with its potential targets.
Results:
The expression levels of miR-641 were downregulated, while the expression levels of nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) were increased in breast cancer cell lines. The in vitro results showed that miR-641 repressed proliferation and migration/invasion and promoted apoptosis of breast cancer cells. NUCKS1, a positive regulator of phosphatidylinositol-3-kinases (PI3K)/protein-serine-threonine kinase (AKT) pathway, was confirmed as a direct target of miR-641. The of treatment of the PI3K agonist, 740Y-P, could abrogate the antioncogenic potentials of miR-641 in breast cancer cells.
Conclusion:
miR-641 functioned as a tumor suppressor through the PI3K/AKT signaling pathway via targeting NUCKS1 in breast cancer.
Insights
MicroRNA-641 (miR-641) acts as a tumor suppressor in breast cancer by inhibiting cell proliferation and migration. It targets NUCKS1, regulating the PI3K/AKT pathway to suppress tumor growth.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) play critical roles in various cancers, including breast cancer.
- Understanding the specific functions of individual miRNAs is essential for developing targeted therapies.
Purpose of the Study:
- To investigate the role and function of miR-641 in breast cancer.
- To elucidate the molecular mechanisms underlying miR-641's action in breast cancer.
Main Methods:
- Real-time PCR was used to determine miR-641 expression in breast cancer cell lines.
- Functional assays (CCK-8, transwell, wound-healing, apoptosis) assessed miR-641's impact on malignant behaviors.
- Luciferase reporter assays identified miR-641's direct targets and regulatory pathways.
Main Results:
- miR-641 expression was downregulated in breast cancer cell lines, with inverse correlation to NUCKS1 levels.
- miR-641 suppressed breast cancer cell proliferation, migration, and invasion, while promoting apoptosis.
- NUCKS1, a PI3K/AKT pathway regulator, was validated as a direct miR-641 target; PI3K agonist treatment reversed miR-641's effects.
Conclusions:
- miR-641 functions as a tumor suppressor in breast cancer.
- The tumor-suppressive role of miR-641 is mediated through targeting NUCKS1 and inhibiting the PI3K/AKT signaling pathway.
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