Long non-coding RNA CDKN2B antisense RNA 1 gene inhibits Gemcitabine sensitivity in bladder urothelial carcinoma

Dalong Xie1, Hui Zhang2, Chao Shang3

  • 1Department of Anatomy, College of Basic Medicine, China Medical University, Shenyang, 110001, China.

Journal of Cancer
|June 26, 2018
PubMed

Insights

High expression of CDKN2B-AS, a long noncoding RNA, is linked to reduced Gemcitabine sensitivity in bladder urothelial carcinoma (BUC). Targeting CDKN2B-AS may improve BUC treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Bladder urothelial carcinoma (BUC) is a prevalent cancer with varying responses to chemotherapy.
  • Gemcitabine is a standard chemotherapeutic agent, but resistance remains a challenge.
  • Long noncoding RNAs (lncRNAs) are emerging as critical regulators in cancer progression and drug resistance.

Purpose of the Study:

  • To investigate the clinical significance of the lncRNA CDKN2B-AS gene in BUC.
  • To determine the effect of CDKN2B-AS on Gemcitabine sensitivity in BUC.
  • To elucidate the underlying molecular mechanisms involving the Wnt signaling pathway.

Main Methods:

  • Real-time quantitative PCR to assess CDKN2B-AS gene expression.
  • CCK-8 assay for cell proliferation and Gemcitabine IC50 determination.
  • Annexin V-FITC/PI staining for apoptosis analysis.
  • Western blotting for protein expression.
  • TOP/FOP luciferase assay to evaluate Wnt signaling pathway activity.

Main Results:

  • CDKN2B-AS was significantly upregulated in BUC tissues and cell lines compared to normal controls.
  • High CDKN2B-AS expression correlated with advanced pathological grade and decreased Gemcitabine sensitivity.
  • CDKN2B-AS expression was higher in Gemcitabine-resistant cells.
  • Knockdown of CDKN2B-AS enhanced Gemcitabine sensitivity and induced cytotoxicity by inactivating the Wnt signaling pathway.

Conclusions:

  • LncRNA CDKN2B-AS is overexpressed in BUC and associated with poor Gemcitabine sensitivity.
  • CDKN2B-AS promotes Gemcitabine resistance in BUC, potentially through the activation of the Wnt signaling pathway.
  • Targeting CDKN2B-AS represents a potential therapeutic strategy to overcome Gemcitabine resistance in BUC.

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