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circDCUN1D4 suppresses tumor metastasis and glycolysis in lung adenocarcinoma by stabilizing TXNIP expression

Yingkuan Liang1,2,3,4, Hui Wang1,2,3, Bing Chen1,2,3

  • 1The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, PR China.

Molecular Therapy. Nucleic Acids
|January 11, 2021
PubMed

Insights

A novel circular RNA, circDCUN1D4, is downregulated in lung cancer, promoting metastasis and glycolysis by interacting with HuR and TXNIP mRNA. Its reduced expression is linked to poor patient survival.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • RNA Biology

Background:

  • Aberrant circular RNA (circRNA) expression is implicated in cancer progression.
  • RNA-binding proteins (RBPs) play a crucial role in regulating circRNA function.
  • Human antigen R (HuR) is an RBP involved in post-transcriptional gene regulation.

Purpose of the Study:

  • To identify and characterize novel circRNAs involved in lung cancer progression.
  • To elucidate the mechanism by which circDCUN1D4 affects lung cancer metastasis and glycolysis.
  • To investigate the clinical significance of circDCUN1D4 in lung adenocarcinoma (LUAD).

Main Methods:

  • Screening of circRNA expression in A549 cells using circBase.
  • Analysis of crosslinking immunoprecipitation (CLIP) data for HuR.
  • In vitro and in vivo assays to assess the impact of circDCUN1D4 depletion on cell invasion and metastasis.
  • RNA immunoprecipitation (RIP) and RNA pull-down assays to confirm interactions.
  • Quantitative real-time PCR and Western blotting to analyze gene and protein expression.

Main Results:

  • A novel circRNA, circDCUN1D4, was identified and found to be downregulated in LUAD tissues.
  • circDCUN1D4 suppresses invasion and metastasis by interacting with HuR and stabilizing TXNIP mRNA.
  • circDCUN1D4 forms a ternary complex with HuR and TXNIP mRNA, inhibiting glycolysis and metastasis.
  • Downregulated circDCUN1D4 correlates with lymph node metastasis and predicts poor overall survival in LUAD patients.

Conclusions:

  • circDCUN1D4 acts as a tumor suppressor in LUAD by inhibiting metastasis and glycolysis.
  • The circDCUN1D4/HuR/TXNIP axis represents a potential therapeutic target for LUAD.
  • circDCUN1D4 is a novel independent prognostic biomarker for LUAD patients.
Keywords:
DCUN1D4HuRLUADRNA binding proteinTXNIPcircDCUN1D4circRNAcircular RNAglycolysismetastasis

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