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The Alteration of MiR-222 and Its Target Genes in Nickel-Induced Tumor

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Abstract

Nickel is an important kind of metal and a necessary trace element in people’s production and livelihood; it is also a well-confirmed human carcinogen. In the past few years, researchers did a large number of studies about the molecular mechanisms of nickel carcinogenesis, and they focused on activation of proto-oncogenes and inactivation of anti-oncogenes caused by gene point mutation, gene deletion, gene amplification, DNA methylation, chromosome condensation, and so on that were induced by nickel. However, the researches on tumorigenic molecular mechanisms regulated by microRNAs (miRNAs) are rare. In this study, we established nickel-induced tumor by injecting Ni3S2 compounds to Wistar Rattus. By establishing a cDNA library of miRNA from rat muscle tumor tissue induced by Ni3S2, we found that the expression of miR-222 was significantly upregulated in tumor tissue compared with the normal tissue. As we expected, the expression levels of target genes of miR-222, CDKN1B and CDKN1C, were downregulated in the nickel-induced tumor. The same alteration of miR-222 and its target genes was also found in malignant 16HBE cells induced with Ni3S2 compounds. We conclude that miR-222 may promote cell proliferation infinitely during nickel-induced tumorigenesis in part by regulating the expression of its target genes CDKN1B and CDKN1C. Our study elucidated a novel molecular mechanism of nickel-induced tumorigenesis.

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Acknowledgments

We thank Dr. Lijuan Zhang for kindly providing 16HBE cell line to our laboratory. This work was supported by the Natural Science Foundation of China (31271120, 31171012, and 81041069), National Key Basic Research Program of China (2011CB965102), and International Cooperation Program of the Ministry of Science and Technology of China (2011DFA30480 and 2011DFB30010).

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Authors and Affiliations

  1. Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai, 200065, China

    Jing Zhang

  2. School of Life Science and Technology, Tongji University, Shanghai, 200092, China

    Jing Zhang, Shunquan Huang, Rongrong Gao & Youjun Wu

  3. Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, 200092, China

    Yang Zhou, Lin Ma, Ruijin Wang, Hongjun Shi & Jun Zhang

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  1. Jing Zhang
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  2. Yang Zhou
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  3. Lin Ma
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  4. Shunquan Huang
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  5. Ruijin Wang
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  7. Youjun Wu
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  8. Hongjun Shi
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  9. Jun Zhang
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Correspondence to Jing Zhang or Jun Zhang.

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Jing Zhang, Yang Zhou, and Lin Ma contributed equally to this work.

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Zhang, J., Zhou, Y., Ma, L. et al. The Alteration of MiR-222 and Its Target Genes in Nickel-Induced Tumor. Biol Trace Elem Res 152, 267–274 (2013). https://doi.org/10.1007/s12011-013-9619-6

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  • DOI: https://doi.org/10.1007/s12011-013-9619-6

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