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RNA-binding protein PCBP2 modulates glioma growth by regulating FHL3

Wei Han1, Zhongshuai Xin, Zhiqiang Zhao

  • 1State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

The Journal of Clinical Investigation
|April 16, 2013
PubMed

Insights

Poly(C)-binding protein 2 (PCBP2) is upregulated in human gliomas. Inhibiting PCBP2 suppresses glioma growth by halting cell-cycle progression and inducing apoptosis, revealing a new pathway for glioma progression.

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • Poly(C)-binding protein 2 (PCBP2) is implicated in gene regulation and human malignancies.
  • PCBP2 interacts with poly(C) motifs in target mRNAs, influencing posttranscriptional and translational processes.

Purpose of the Study:

  • To investigate the role of PCBP2 in human glioma.
  • To identify PCBP2 targets and elucidate its mechanism in glioma progression.

Main Methods:

  • Analysis of PCBP2 expression in glioma tissues and cell lines.
  • In vitro and in vivo knockdown of PCBP2 in glioma models.
  • RNA immunoprecipitation coupled with ChIP (RIP-ChIP) arrays to identify PCBP2 targets.
  • mRNA stability assays and functional studies of FHL3.

Main Results:

  • PCBP2 is upregulated in human glioma.
  • PCBP2 knockdown inhibits glioma growth, cell-cycle progression, and induces apoptosis.
  • Thirty-five putative PCBP2 target mRNAs were identified, including FHL3.
  • PCBP2 knockdown stabilizes FHL3 mRNA, increasing its expression.
  • FHL3 overexpression attenuates glioma cell growth and induces apoptosis.

Conclusions:

  • PCBP2 plays a significant role in promoting human glioma progression.
  • PCBP2 regulates glioma through modulation of FHL3 expression and stability.
  • This study identifies a novel PCBP2-FHL3 pathway critical for glioma development.

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