hnRNP G elicits tumor-suppressive activity in part by upregulating the expression of Txnip.
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| Abstract |
Heterogeneous nuclear ribonuclearproteins (hnRNPs) are nucleic acid-binding proteins and have critical roles in DNA repair, telomere regulation, and transcriptional gene regulation. Previously, we showed that hnRNP G has tumor-suppressive activity in human oral squamous cell carcinoma cells. Therefore, the identification of hnRNP G target genes is important for understanding the function of hnRNP G and its tumor-suppressive activity. In this study, we identify a known tumor suppressor gene, thioredoxin-interacting protein (Txnip) gene as a novel target of hnRNP G. Expression of Txnip is upregulated by wild-type (wt) hnRNP G but not by a suppression-defective mutant hnRNP G (K22R) in human squamous cell carcinoma. Wt hnRNP G binds and transactivates the Txnip promoter in vivo, whereas the K22R mutant does not. Furthermore, overexpression of Txnip alone in cancer cells leads to the inhibition of anchorage-independent growth and in vivo tumorigenicity in immunocompromised mice, suggesting a reversion of the transformation phenotype. These studies indicate that hnRNP G promotes the expression of Txnip and mediates its tumor-suppressive effect.
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| Authors | Ki-Hyuk Shin, Reuben H Kim, Roy H Kim, Mo K Kang, No-Hee Park |
| Journal | Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 372 Issue 4 Pg. 880-5 (Aug 08 2008) ISSN: 1090-2104 [Electronic] United States |
| PMID | 18541147 (Publication Type: Journal Article, Research Support, N.I.H., Extramural) |
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