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C10ORF97 is a novel tumor-suppressor gene of non-small-cell lung cancer and a functional variant of this gene increases the risk of non-small-cell lung cancer

Oncogene volume 30, pages 4107–4117 (2011)Cite this article

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Abstract

In an earlier study we showed that C10ORF97 (chromosome-10, open reading frame-97) was expressed in almost all of the tissues and cell lines tested, and that it inhibited the growth of seven tumor cell lines, including two lung carcinoma cell lines (A549 and PG). Here, we show that C10ORF97 is downregulated in non-small-cell lung cancer (NSCLC) tissue compared with normal lung tissue. Overexpression of C10ORF97 significantly suppressed human lung carcinoma A549 cell growth (proliferation and anchorage-independent growth in soft agar) and motility (migration and adhesion). This tumor-suppressive function of C10ORF97 was also verified in vivo. We further found that C10ORF97 caused G1 arrest of A549 cells and modulated the expression level of several cell-cycle regulators (such as CDK2, cyclin-E and p27). These effects of C10ORF97 were mediated by physical association between C10ORF97 and Jun-activating domain-binding protein-1 (JAB1), and blocking of JAB1-mediated translocation of p27 from the nucleus to the cytoplasm. Together, these results indicated that C10ORF97 functions as a novel tumor suppressor by modulating several key G1/S-regulatory proteins by interacting with JAB1. These findings led us to hypothesize that a single-nucleotide polymorphism (SNP) in the C10ORF97 gene that affects its expression might be associated with susceptibility to NSCLC. SNP216 C>T (rs2297882) in the C10ORF97 Kozak sequence was identified, and allele T of SNP216 suppressed C10ORF97 expression in vitro and in vivo. Furthermore, the TT genotype of SNP216 was associated with an increased risk of NSCLC (adjusted odds ratio=1.73 (95% confidence interval: 1.33–2.25), P=4.6 × 10–5). These data indicated that C10ORF97 is a tumor suppressor of NSCLC progression and C10ORF97-SNP216 may serve as a predictor of NSCLC.

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Acknowledgements

We thank Professor Gu Xiaocheng and Zheng Xiaofeng (Department of Biochemistry and Molecular Biology, College of Life Sciences, Peking University, Beijing, China) for preparation and purification of the C10ORF97 protein. Sources of support: This study was supported by the National High Technology Research and Development Program of China (863 Program, No. 2006AA02Z477 to RH), the National Natural Science Foundation of China (No. 30500199 to JC and No. 30900809 to YS) and the Foundation of Beijing Municipal Committee of Science and Technology (No. D0905001040631 to JJ).

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  1. Y Shi, J Chen and Z Li: These authors contributed equally to this work.

Authors and Affiliations

  1. Sino-German Laboratory for Molecular Medicine, Key Laboratory for Clinical Cardiovascular Genetics, Ministry of Education, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China

    Y Shi, J Chen, Z Zhang, H Yu, K Sun, X Wang, X Song, Y Wang, Y Zhen, T Yang, K Lou, Y Zhang & R Hui

  2. Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China

    Y Shi

  3. Department of Surgery, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital and Institute, Beijing, China

    Z Li, G Zhang, Y Hu & J Ji

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Shi, Y., Chen, J., Li, Z. et al. C10ORF97 is a novel tumor-suppressor gene of non-small-cell lung cancer and a functional variant of this gene increases the risk of non-small-cell lung cancer. Oncogene 30, 4107–4117 (2011). https://doi.org/10.1038/onc.2011.116

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