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UNC5B-AS1 promoted ovarian cancer progression by regulating the H3K27me on NDRG2 via EZH2
Hao Wang1, Hong Su2, Yujie Tan1
1Department of Obstetrics, Luoyang Central Hospital Affiliated to Zhengzhou University, Zhongzhouzhong Road 288, XiGong District, Luoyang, 471009, Henan, China.
Abstract:
The role of long non-coding RNAs (lncRNAs) in tumorigenesis and development of ovarian cancer (OC) has caught the attention of scientists. UNC5B antisense RNA 1 (UNC5B-AS1) is a newly identified carcinogenic lncRNA in thyroid papillary carcinoma, but its role in OC remains unclear. This study is proposed to investigate the function and mechanism of UNC5B-AS1 in OC. UNC5B-AS1 expression in OC samples was obtained from gene expression profiling interactive analysis (GEPIA) based on The Cancer Genome Atlas data. Gene expressions were detected by quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. Biological functions of UNC5B-AS1 were assessed by cell counting kit-8, colony formation, and caspase-3 analysis. GEPIA revealed the UNC5B-AS1 upregulation in OC samples. RT-qPCR assay confirmed the upregulation of UNC5B-AS1 in OC cells. Functionally, depletion of UCN5B-AS1 hindered proliferation and prompted apoptosis in OC cells. Mechanistically, we found that UNC5B-AS1 interacted with zeste 2 polycomb repressive complex 2 subunit (EZH2) to trigger trimethylation of histone H3 at lysine 27 (H3K27me3) on N-myc downstream regulated gene-2 (NDRG2) promoter and epigenetically repressed NDRG2. Rescue assay indicated the participation of NDRG2 in the regulation of UNC5B-AS1 on OC progression. Together, we first illustrated that UNC5B-AS1 promoted OC progression by regulating the H3K27me on NDRG2 via EZH2, indicating UNC5B-AS1 as a potential molecular target for OC treatment.
Insights
Long non-coding RNA UNC5B-AS1 promotes ovarian cancer (OC) progression by epigenetically repressing NDRG2 via EZH2. This study identifies UNC5B-AS1 as a potential therapeutic target for OC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer development.
- The specific function of UNC5B antisense RNA 1 (UNC5B-AS1) in ovarian cancer (OC) is currently unknown.
- UNC5B-AS1 has been identified as a carcinogenic lncRNA in other cancers, suggesting a potential role in OC.
Purpose of the Study:
- To investigate the functional role of UNC5B-AS1 in ovarian cancer (OC).
- To elucidate the underlying molecular mechanism of UNC5B-AS1 in OC progression.
- To assess UNC5B-AS1 as a potential therapeutic target for OC.
Main Methods:
- Analysis of UNC5B-AS1 expression in OC samples using The Cancer Genome Atlas (TCGA) data via GEPIA.
- Validation of gene and protein expression using quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot.
- Functional assays including cell counting kit-8, colony formation, and caspase-3 analysis to assess proliferation and apoptosis. Mechanistic studies involved assessing interactions with EZH2 and its effect on NDRG2 promoter methylation.
Main Results:
- UNC5B-AS1 was found to be significantly upregulated in OC tissues and cell lines.
- Depletion of UNC5B-AS1 inhibited OC cell proliferation and induced apoptosis.
- UNC5B-AS1 was shown to interact with EZH2, leading to H3K27me3 on the NDRG2 promoter, thereby epigenetically repressing NDRG2 expression. NDRG2 was confirmed to be involved in UNC5B-AS1-mediated OC progression.
Conclusions:
- UNC5B-AS1 promotes ovarian cancer progression.
- The mechanism involves the UNC5B-AS1/EZH2 axis, which epigenetically represses NDRG2.
- UNC5B-AS1 represents a promising molecular target for ovarian cancer therapy.
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