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Published on: June 9, 2023
MicroRNA-494 inhibits breast cancer progression by directly targeting PAK1
Meng-Na Zhan1, Xiao-Ting Yu2, Jun Tang3
1Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology and Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
Abstract:
MicroRNA (miRNA) is involved in the progression and metastasis of diverse human cancers, including breast cancer, as strong evidence has been found that miRNAs can act as oncogenes or tumor suppressor genes. Here, we show that miR-494 is decreased in human breast cancer specimens and breast cancer cell lines. Ectopic expression of miR-494 in basal-like breast cancer cell lines MDA-MB-231-LUC-D2H3LN and BT-549 inhibits clonogenic ability and metastasis-relevant traits in vitro. Moreover, ectopic expression of miR-494 suppresses neoplasm initiation as well as pulmonary metastasis in vivo. Further studies have identified PAK1, as a direct target gene of miR-494, contributes to the functions of miR-494. Remarkably, the expression of PAK1 is inversely correlated with the level of miR-494 in human breast cancer samples. Furthermore, re-expression of PAK1 partially reverses miR-494-mediated proliferative and clonogenic inhibition as well as migration and invasion suppression in breast cancer cells. Taken together, these findings highlight an important role for miR-494 in the regulation of progression and metastatic potential of breast cancer and suggest a potential application of miR-494 in breast cancer treatment.
Insights
MicroRNA 494 (miR-494) acts as a tumor suppressor in breast cancer. Lower miR-494 levels correlate with increased cancer progression and metastasis, suggesting its therapeutic potential.
Area of Science:
- Molecular Biology
- Oncology
- Cancer Research
Background:
- MicroRNAs (miRNAs) play critical roles in cancer development and metastasis, functioning as oncogenes or tumor suppressors.
- Evidence suggests miRNAs are implicated in various human cancers, including breast cancer.
Purpose of the Study:
- To investigate the role of miR-494 in human breast cancer progression and metastasis.
- To identify the molecular mechanisms underlying miR-494's function in breast cancer.
Main Methods:
- Quantitative analysis of miR-494 expression in breast cancer specimens and cell lines.
- In vitro studies using breast cancer cell lines to assess the effects of miR-494 ectopic expression on clonogenic ability, migration, and invasion.
- In vivo studies to evaluate the impact of miR-494 on tumor initiation and pulmonary metastasis.
- Identification of PAK1 as a direct target gene of miR-494 and assessment of its role in miR-494-mediated effects.
Main Results:
- miR-494 expression is significantly decreased in human breast cancer tissues and cell lines.
- Ectopic expression of miR-494 inhibits breast cancer cell proliferation, clonogenic ability, migration, and invasion in vitro.
- miR-494 suppresses tumor initiation and pulmonary metastasis in vivo.
- PAK1 is a direct target of miR-494, and its expression is inversely correlated with miR-494 levels in breast cancer samples.
- Re-expression of PAK1 partially reverses the inhibitory effects of miR-494 on breast cancer cell proliferation and metastasis.
Conclusions:
- miR-494 functions as a tumor suppressor in breast cancer by inhibiting progression and metastasis.
- The miR-494/PAK1 axis is a key regulatory pathway in breast cancer.
- miR-494 holds potential as a therapeutic agent for breast cancer treatment.
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