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A novel lncRNA NR4A1AS up-regulates orphan nuclear receptor NR4A1 expression by blocking UPF1-mediated mRNA

Xina Xie1,2, Jiatian Lin3, Jianlan Liu4

  • 1Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, Institute of Translational Medicine, First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, China.

Clinical Science (London, England : 1979)
|June 30, 2019
PubMed

Insights

A novel long non-coding RNA, NR4A1AS, promotes colorectal cancer (CRC) by stabilizing NR4A1 mRNA, inhibiting UPF1-mediated decay. NR4A1AS inhibition suppressed tumor growth and metastasis, suggesting its potential as an anti-CRC therapeutic target.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • RNA Biology

Background:

  • Long non-coding RNAs (lncRNAs) are implicated in cancer development.
  • Nuclear receptor subfamily 4 group A member 1 (NR4A1) is an oncogene in colorectal cancer (CRC).
  • The regulatory mechanisms of NR4A1 by lncRNAs in CRC are not well understood.

Purpose of the Study:

  • To identify lncRNAs regulating NR4A1 expression in CRC.
  • To elucidate the molecular mechanisms underlying NR4A1 regulation by lncRNAs in CRC.
  • To evaluate the therapeutic potential of NR4A1AS in CRC.

Main Methods:

  • Identification of NR4A1 antisense lncRNA (NR4A1AS) using RACE.
  • Correlation analysis of NR4A1AS and NR4A1 mRNA levels in CRC tissues.
  • Assessment of NR4A1AS function via siRNA knockdown, RNA immunoprecipitation (RIP), and in vitro/in vivo assays.

Main Results:

  • NR4A1AS was identified as an antisense lncRNA upregulated in CRC and positively correlated with NR4A1 mRNA.
  • NR4A1AS stabilizes NR4A1 mRNA by forming RNA-RNA complexes, upregulating NR4A1 expression and inhibiting UPF1-mediated decay.
  • NR4A1AS depletion suppressed CRC cell proliferation, migration, invasion, and induced apoptosis and cell cycle arrest, mimicking NR4A1 knockdown.

Conclusions:

  • NR4A1AS promotes CRC progression by stabilizing NR4A1 mRNA and blocking UPF1-mediated decay.
  • NR4A1AS regulates CRC cell growth, metastasis, apoptosis, and cell cycle via NR4A1.
  • NR4A1AS represents a potential therapeutic target for RNA-based anti-CRC drug development.
Keywords:
Colorectal cancerLncRNA NR4A1ASNR4A1UPF1mRNA stability

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