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Published on: August 2, 2024
MiR181c inhibits ovarian cancer metastasis and progression by targeting PRKCD expression
Lijuan Yao1, Li Wang1, Fengxia Li2
1Department of Gynaecology and Obstetrics, Affiliated Hospital of Binzhou Medical College Binzhou 256603, China.
Abstract:
MicroRNAs (miRNAs) regulate many important cancer related gene expression in the posttranscriptional process. Dysregulated expression of miRNAs has been observed in numerous human cancers including ovarian cancer. In this study, we found that the expression of the miR-181c was significantly decreased in ovarian cancer tissue and in tissues with lymph node metastasis when compared with their control samples, respectively. Moreover, among pathological stages, the expression of miR-181c was significantly decreased in the tissues with IV stage compared with other stages. In vitro, miR-181c significantly inhibited the proliferation, metastasis of A2780 cell line, and induced G1 phase arrest. Through bioinformatics prediction, protein kinase C delta (PRKCD) was identified as a target gene of miR-181c. Western blot results showed that PRKCD was increased in ovarian cancer tissue, in tissues with lymph node metastasis and IV stage of ovarian cancer pathological samples. After knocking down PRKCD, the cell cycle of A2780 cells was also arrested in G1 phase. The proliferation and the metastasis of A2780 cells were reduced. The dual luciferase reporter experiments showed that miR-181c regulated the expression of PRKCD by combining with its 3'UTR. These results indicate that miR-181c inhibits ovarian cancer metastasis and progression by targeting PRKCD expression.
Insights
MicroRNA-181c (miR-181c) is decreased in ovarian cancer, inhibiting tumor progression and metastasis by targeting protein kinase C delta (PRKCD). Lower miR-181c levels correlate with advanced stages and lymph node involvement.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- MicroRNAs (miRNAs) are key posttranscriptional regulators of gene expression.
- Dysregulated miRNA expression is implicated in various cancers, including ovarian cancer.
- Ovarian cancer progression and metastasis are complex processes influenced by genetic alterations.
Purpose of the Study:
- To investigate the role of miR-181c in ovarian cancer.
- To identify the downstream targets of miR-181c in ovarian cancer.
- To elucidate the mechanism by which miR-181c affects ovarian cancer progression and metastasis.
Main Methods:
- Quantitative real-time PCR to measure miR-181c expression in ovarian cancer tissues and cell lines.
- In vitro functional assays (proliferation, migration, invasion) using A2780 cells.
- Bioinformatics analysis and dual-luciferase reporter assays to identify and validate miR-181c targets.
- Western blotting to assess protein expression levels.
Main Results:
- miR-181c expression was significantly decreased in ovarian cancer tissues, particularly in those with lymph node metastasis and advanced pathological stage (IV).
- Overexpression of miR-181c in A2780 cells inhibited proliferation, metastasis, and induced G1 phase arrest.
- Protein kinase C delta (PRKCD) was identified as a direct target of miR-181c, with its expression inversely correlated with miR-181c levels in ovarian cancer samples.
- Knockdown of PRKCD mimicked the effects of miR-181c, reducing cell proliferation, metastasis, and inducing G1 arrest.
Conclusions:
- miR-181c acts as a tumor suppressor in ovarian cancer.
- The miR-181c/PRKCD axis plays a critical role in regulating ovarian cancer cell proliferation, metastasis, and cell cycle progression.
- miR-181c may serve as a potential therapeutic target or biomarker for ovarian cancer.
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