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  • Original Article
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Hypoxic regulation of stability of connective tissue growth factor/CCN2 mRNA by 3′-untranslated region interacting with a cellular protein in human chondrosarcoma cells

Oncogene volume 25, pages 1099–1110 (2006)Cite this article

Abstract

Connective tissue growth factor (CTGF/CCN2) can be induced by various forms of stress such as exposure to high glucose, mechanical load, or hypoxia. Here, we investigated the molecular mechanism involved in the induction of ctgf/ccn2 by hypoxia in a human chondrosarcoma cell line, HCS-2/8. Hypoxia increased the ctgf/ccn2 mRNA level by altering the 3′-untranslated region (UTR)-mediated mRNA stability without requiring de novo protein synthesis. After a series of extensive analyses, we eventually found that the cis-repressive element of 84 bases within the 3′-UTR specifically bound to a cytoplasmic/nuclear protein. By conducting a UV crosslinking assay, we found the cytoplasmic/nuclear protein to be a 35 kDa molecule that bound to the cis-element in a hypoxia-inducible manner. These results suggest that a cis-element in the 3′-UTR of ctgf/ccn2 mRNA and trans-factor counterpart(s) play an important role in the post-transcriptional regulation by determining the stability of ctgf/ccn2 mRNA.

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Acknowledgements

This work was supported in part by the programs Grants-in-Aid for Scientific Research (SK, SK, MT) and Exploratory Research (MT) of the Ministry of Education, Science, Sports, and Culture of Japan; Grants-in-Aid for JSPS Fellows (SK); Grants-in-Aid for Specific Diseases of the Ministry of Public Health and Welfare of Japan (MT); and by grants from the Naito Foundation (MT), the Nakatomi Health Science Foundation (SK, MT), the Foundation for Growth Science in Japan (MT), the Sumitomo Foundation (MT), and Research for the Future Programme of The Japan Society for the Promotion of Science (JSPS; Project: Biological Tissue Engineering, JSPS-RFTF98I00201). We thank Drs Tohru Nakanishi and Takanori Eguchi for their helpful suggestions, Kazumi Ohyama for technical assistance, and Yuki Nonami for secretarial help.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    S Kondo, S Kubota, Y Mukudai, N Moritani, T Nishida & M Takigawa

  2. Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan

    S Kondo, N Moritani & T Sugahara

  3. Biosciences Business Division, Nichirei Corporation, Chuo-ku, Tokyo, Japan

    H Matsushita & S Matsumoto

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  1. S Kondo
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Correspondence to M Takigawa.

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Kondo, S., Kubota, S., Mukudai, Y. et al. Hypoxic regulation of stability of connective tissue growth factor/CCN2 mRNA by 3′-untranslated region interacting with a cellular protein in human chondrosarcoma cells. Oncogene 25, 1099–1110 (2006). https://doi.org/10.1038/sj.onc.1209129

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