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.

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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