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EF1A1-actin interactions alter mRNA stability to determine differential osteopontin expression in HepG2 and Hep3B cells.

Publication ,  Journal Article
Zhang, J; Guo, H; Mi, Z; Gao, C; Bhattacharya, S; Li, J; Kuo, PC
Published in: Exp Cell Res
January 15, 2009

Cancer progression depends on an accumulation of metastasis-supporting physiological changes which are regulated by cell signaling molecules. One such molecule, osteopontin (OPN), is a secreted phosphoprotein which mediates increased cellular migratory and invasive behavior, increased metastasis, protection from apoptosis, promotion of colony formation and 3D growth ability, induction of tumor-associated inflammatory cells, and induction of expression of angiogenic factors. Studies show that OPN expression is controlled by complex regulatory pathways at the transcriptional level in several cancers, but the molecular mechanisms which determine expression of OPN in HCC are largely unknown. In HepG2 and Hep3B tumor cell lines that differentially express OPN mRNA and protein, we identify elongation translation factor-1A1 (EF1A1) to be the trans-acting factor regulating differential OPN mRNA stability between HepG2 and Hep3B cell lines and characterize its interactions with G- and F-actin. EF1A1 binds to the OPN 5'-UTR to regulate OPN mRNA half-life. EF1A1 binds to actin in Hep3B cells. Pharmacologic manipulation to increase the G:F actin ratio in Hep3B increases OPN mRNA half-life and protein expression with simultaneous decrease in EF1A1 binding to OPN 5'-UTR. The converse findings were noted in HepG2 cells. Overall, our results suggest that EF1A1 regulation of OPN mRNA stability is actin dependent. EF1A1 has not been previously identified as a regulatory factor in OPN expression in cancer.

Duke Scholars

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Published In

Exp Cell Res

DOI

EISSN

1090-2422

Publication Date

January 15, 2009

Volume

315

Issue

2

Start / End Page

304 / 312

Location

United States

Related Subject Headings

  • Transfection
  • Sequence Deletion
  • Regulatory Elements, Transcriptional
  • RNA, Small Interfering
  • RNA Stability
  • Protein Binding
  • Peptide Elongation Factor 1
  • Osteopontin
  • Marine Toxins
  • Liver Neoplasms
 

Citation

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Zhang, J., Guo, H., Mi, Z., Gao, C., Bhattacharya, S., Li, J., & Kuo, P. C. (2009). EF1A1-actin interactions alter mRNA stability to determine differential osteopontin expression in HepG2 and Hep3B cells. Exp Cell Res, 315(2), 304–312. https://doi.org/10.1016/j.yexcr.2008.10.042
Zhang, Jinping, Hongtao Guo, Zhiyong Mi, Chengjiang Gao, Syamal Bhattacharya, Jiansheng Li, and Paul C. Kuo. “EF1A1-actin interactions alter mRNA stability to determine differential osteopontin expression in HepG2 and Hep3B cells.Exp Cell Res 315, no. 2 (January 15, 2009): 304–12. https://doi.org/10.1016/j.yexcr.2008.10.042.
Zhang J, Guo H, Mi Z, Gao C, Bhattacharya S, Li J, et al. EF1A1-actin interactions alter mRNA stability to determine differential osteopontin expression in HepG2 and Hep3B cells. Exp Cell Res. 2009 Jan 15;315(2):304–12.
Zhang, Jinping, et al. “EF1A1-actin interactions alter mRNA stability to determine differential osteopontin expression in HepG2 and Hep3B cells.Exp Cell Res, vol. 315, no. 2, Jan. 2009, pp. 304–12. Pubmed, doi:10.1016/j.yexcr.2008.10.042.
Zhang J, Guo H, Mi Z, Gao C, Bhattacharya S, Li J, Kuo PC. EF1A1-actin interactions alter mRNA stability to determine differential osteopontin expression in HepG2 and Hep3B cells. Exp Cell Res. 2009 Jan 15;315(2):304–312.
Journal cover image

Published In

Exp Cell Res

DOI

EISSN

1090-2422

Publication Date

January 15, 2009

Volume

315

Issue

2

Start / End Page

304 / 312

Location

United States

Related Subject Headings

  • Transfection
  • Sequence Deletion
  • Regulatory Elements, Transcriptional
  • RNA, Small Interfering
  • RNA Stability
  • Protein Binding
  • Peptide Elongation Factor 1
  • Osteopontin
  • Marine Toxins
  • Liver Neoplasms