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The long non-coding RNA DDX11-AS1 facilitates cell progression and oxaliplatin resistance via regulating miR-326/IRS1

W Song1, Y Qian, M-H Zhang

  • 1Department of Gastroenterology, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, China. rhxbod@163.com.

European Review for Medical and Pharmacological Sciences
|April 10, 2020
PubMed
Abstract

Insights

The long non-coding RNA DDX11-AS1 promotes gastric cancer progression and oxaliplatin resistance by targeting miR-326 and increasing IRS1 expression. This suggests DDX11-AS1 as a potential therapeutic target for gastric cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Gastric cancer (GC) exhibits resistance to oxaliplatin (OXA) chemotherapy.
  • Long non-coding RNAs (lncRNAs) play crucial roles in cancer progression and drug resistance.
  • DDX11 antisense RNA 1 (DDX11-AS1) is implicated in various cancers.

Purpose of the Study:

  • To investigate the role of DDX11-AS1 in oxaliplatin resistance in gastric cancer.
  • To elucidate the molecular mechanism underlying DDX11-AS1's function in GC chemoresistance.

Main Methods:

  • Quantitative Real-time polymerase chain reaction (qRT-PCR) to measure RNA levels.
  • Cellular assays (MTT, Transwell, flow cytometry) to assess proliferation, migration, invasion, and apoptosis.
  • Western blot for protein level detection.
  • Dual-Luciferase reporter and RNA immunoprecipitation (RIP) assays to confirm molecular interactions.
  • Xenograft models for in vivo validation.

Main Results:

  • DDX11-AS1 was significantly overexpressed in oxaliplatin-resistant GC tissues and cells.
  • Knockdown of DDX11-AS1 inhibited proliferation, migration, invasion, and oxaliplatin resistance while promoting apoptosis in GC cells.
  • DDX11-AS1 was found to directly target microRNA-326 (miR-326), and miR-326 targeted insulin receptor substrate 1 (IRS1).
  • Silencing DDX11-AS1 repressed GC progression and oxaliplatin resistance by down-regulating IRS1 via sponging miR-326, both in vitro and in vivo.

Conclusions:

  • DDX11-AS1 accelerates gastric cancer progression and oxaliplatin chemoresistance.
  • The mechanism involves DDX11-AS1 sponging miR-326 to increase IRS1 expression.
  • DDX11-AS1 represents a potential prognostic biomarker and therapeutic target for gastric cancer.

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