Related Experiment Video

Updated: Jun 25, 2025

Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation
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DRAIC mediates hnRNPA2B1 stability and m6A-modified IGF1R instability to inhibit tumor progression

Ya Wen1,2,3, Xiwang Yang2, Yifei Li2,4

  • 1Medical College, Guizhou University, Guiyang, 550025, China.

Oncogene
|May 29, 2024
PubMed

Insights

Downregulated RNA in Cancer (DRAIC) suppresses clear cell Renal Carcinoma (ccRCC) by stabilizing hnRNPA2B1, which then degrades IGF1R mRNA via m6A modification, inhibiting tumor progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Type 1 insulin-like growth factor receptor (IGF1R) is crucial in cancer development.
  • The posttranscriptional regulation of IGF1R, particularly via N6-methyladenosine (m6A) modification, is not well understood.
  • Clear cell Renal Carcinoma (ccRCC) is a major subtype of kidney cancer with complex regulatory mechanisms.

Purpose of the Study:

  • To investigate the role of the lncRNA Downregulated RNA in Cancer (DRAIC) in ccRCC progression.
  • To elucidate the molecular mechanism by which DRAIC affects tumor growth and metastasis.
  • To identify potential therapeutic targets within the DRAIC regulatory pathway.

Main Methods:

  • Investigated the interaction between DRAIC and heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1).
  • Assessed the effect of DRAIC on hnRNPA2B1 protein stability and its interaction with E3 ligase FBXO11.
  • Analyzed the impact of the DRAIC/hnRNPA2B1 axis on m6A-modified IGF1R mRNA stability and ccRCC progression.
  • Identified specific m6A modification sites on IGF1R mRNA.

Main Results:

  • DRAIC was found to suppress tumor growth and metastasis in ccRCC.
  • DRAIC enhances hnRNPA2B1 protein stability by inhibiting FBXO11-mediated ubiquitination and degradation.
  • hnRNPA2B1 destabilizes m6A-modified IGF1R mRNA, thereby inhibiting ccRCC progression.
  • Four m6A modification sites on IGF1R mRNA were identified as critical for its degradation.

Conclusions:

  • The DRAIC/hnRNPA2B1 axis regulates IGF1R mRNA stability in an m6A-dependent manner.
  • This study reveals a novel mechanism linking m6A-modified RNA and ubiquitin-modified protein.
  • The DRAIC/hnRNPA2B1/FBXO11/IGF1R axis represents a promising therapeutic target for ccRCC treatment.

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