RNA-binding protein PCBP2 modulates glioma growth by regulating FHL3
Wei Han, … , Boqin Qiang, Xiaozhong Peng
Wei Han, … , Boqin Qiang, Xiaozhong Peng
Published April 15, 2013
Citation Information: J Clin Invest. 2013;123(5):2103-2118. https://doi.org/10.1172/JCI61820.
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RNA-binding protein PCBP2 modulates glioma growth by regulating FHL3

Abstract

PCBP2 is a member of the poly(C)-binding protein (PCBP) family, which plays an important role in posttranscriptional and translational regulation by interacting with single-stranded poly(C) motifs in target mRNAs. Several PCBP family members have been reported to be involved in human malignancies. Here, we show that PCBP2 is upregulated in human glioma tissues and cell lines. Knockdown of PCBP2 inhibited glioma growth in vitro and in vivo through inhibition of cell-cycle progression and induction of caspase-3–mediated apoptosis. Thirty-five mRNAs were identified as putative PCBP2 targets/interactors using RIP-ChIP protein-RNA interaction arrays in a human glioma cell line, T98G. Four-and-a-half LIM domain 3 (FHL3) mRNA was downregulated in human gliomas and was identified as a PCBP2 target. Knockdown of PCBP2 enhanced the expression of FHL3 by stabilizing its mRNA. Overexpression of FHL3 attenuated cell growth and induced apoptosis. This study establishes a link between PCBP2 and FHL3 proteins and identifies a new pathway for regulating glioma progression.

Authors

Wei Han, Zhongshuai Xin, Zhiqiang Zhao, Wen Bao, Xihua Lin, Bin Yin, Jizong Zhao, Jiangang Yuan, Boqin Qiang, Xiaozhong Peng

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Figure 1

PCBP2 is upregulated in glioma tissues and cell lines compared with normal brain tissues and normal human astrocytes.

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PCBP2 is upregulated in glioma tissues and cell lines compared with norm...
(A) Real-time PCR analysis of PCBP2 in 2 normal brain tissues (N1, N2) and 26 glioma tissues (T1–T9 grade II, T10–T18 grade III, and T19–T26 grade IV). Columns represent means and bars represent SD. (B) Representative Western blot showing PCBP2 protein levels in 2 normal brain tissues and 27 glioma tissues. β-Actin was used as a loading control. (C) Immunohistochemical staining of PCBP2 in glioma (Grade II, Grade III, Grade IV) and pericarcinous tissues (Normal) using anti-human PCBP2 antibodies. There was no staining with rabbit IgG. Original magnification, ×400. (D) Real-time PCR analysis of PCBP2 in 2 normal human astrocyte cell lines (NHA and HA) and 5 glioma cell lines (T98G, A172, U251, U87MG, and CCF-STTG1). (E) Representative Western blot showing PCBP2 protein levels in 2 NHA cell lines and the 5 indicated glioma cell lines.