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LncRNA PCAT-1 plays an oncogenic role in epithelial ovarian cancer by modulating cyclinD1/CDK4 expression
Can Ding1, Ruqiong Wei1, Raquel Alarcón Rodríguez1
1Department of Nursing, Physiotherapy and Medicine, Universidad de Almería Almería, Spain.
Abstract:
Epithelial ovarian cancer is one of the most common causes of gynecological cancer deaths. The knockdown of LncRNA PCAT-1 has been reported to suppress tumor growth in various kinds of cancers, including esophageal cancer, breast cancer, bladder cancer, and hepatocellular carcinoma. However, its function in epithelial ovarian cancer (EOC) is still unclear. In the present study, the expression of LncRNA PCAT-1 was investigated. The results indicate that the expression of LncRNA PCAT-1 is up-regulated in EOC tissues compared with non-cancer controls by reverse transcription-quantitative polymerase chain reaction analysis (RT-qPCR), and its higher expression is always associated with larger tumor sizes and advanced tumor grades in patients with EOC. In addition, silencing PCAT-1 in the EOC cell lines SKOV3 and OVCAR3 significantly inhibits cell proliferation, migration and invasion, which is also shown by cell cycle assays, as the proportion of cells in G0/G1 phase is dramatically increased after knocking down PCAT1. Finally, it is observed that PCAT-1's knockdown significantly decreased the levels of cyclin D1 and CDK4 protein expression. Taken together, LncRNA PCAT-1's oncogenic role in EOC by mediating cyclin D1/CDK4 is demonstrated, indicating it is a potential target for EOC treatment.
Insights
Long non-coding RNA PCAT-1 is upregulated in epithelial ovarian cancer (EOC), promoting tumor growth and progression. Silencing PCAT-1 inhibits EOC cell proliferation and invasion by downregulating cyclin D1 and CDK4, suggesting PCAT-1 as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Epithelial ovarian cancer (EOC) is a leading cause of gynecological cancer mortality.
- The role of long non-coding RNA PCAT-1 in EOC remains largely uncharacterized.
- PCAT-1 has demonstrated tumor-suppressive functions in other cancer types.
Purpose of the Study:
- To investigate the expression and function of LncRNA PCAT-1 in epithelial ovarian cancer.
- To determine the association between PCAT-1 expression and clinicopathological features of EOC.
- To elucidate the underlying molecular mechanisms of PCAT-1's role in EOC progression.
Main Methods:
- Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for gene expression analysis.
- In vitro assays including cell proliferation, migration, invasion, and cell cycle analysis.
- Western blot analysis to assess protein expression levels of cyclin D1 and CDK4.
Main Results:
- LncRNA PCAT-1 expression is significantly upregulated in EOC tissues compared to non-cancerous controls.
- Higher PCAT-1 expression correlates with larger tumor size and advanced tumor grade in EOC patients.
- Silencing PCAT-1 in EOC cell lines (SKOV3, OVCAR3) inhibited cell proliferation, migration, and invasion, and increased G0/G1 phase arrest.
- PCAT-1 knockdown led to decreased protein expression of cyclin D1 and CDK4.
Conclusions:
- LncRNA PCAT-1 acts as an oncogene in epithelial ovarian cancer.
- PCAT-1 promotes EOC progression by mediating the cyclin D1/CDK4 pathway.
- Targeting LncRNA PCAT-1 presents a potential therapeutic strategy for EOC treatment.
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