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The role of c2orf68 and PI3K/Akt/mTOR pathway in human colorectal cancer

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Abstract

The aim of the research is to determine whether c2orf68 gene plays a role in the carcinogenesis of human colorectal cancer and to study the function of c2orf68 belonging to the UPF0561 family. The mRNA expression levels of c2orf68 were examined in 30 pairs of human colorectal adenocarcinoma tissues and adjacent normal colorectal tissues by qRT-PCR. The SW480 and SW620 cell lines were transfected with siRNA against the c2orf68 gene and set gene. The expressed mRNA levels of Akt, PI3K, Bax, Bcl-2, caspase3, c-Myc, cyclinD1, pp2a and set were determined by qRT-PCR, and the protein levels of C2ORF68, c-Myc, PP2A and SET were examined by Western blot. Cell proliferation was tested by MTT assay, and apoptosis and cell cycle were studied by flow cytometry. Cancer metastasis assay was performed by transwell chamber. The c2orf68 mRNA expression was down-regulated in 63.33 % of the cancer samples, and a positive correlation was found between the mRNA expression of c-Myc and pp2a that of c2orf68. Meanwhile, there was a negative correlation between the mRNA expression of c2orf68 and set. The c2orf68 mRNA was significantly down-regulated in SW480−c2orf68 and SW620−c2orf68 cells. The inhibitory rate in the two cell lines was, respectively, 65.2 and 71.6 % by qRT-PCR. A 22.7 % inhibition on cell proliferation in SW480−c2orf68 cells and a 21.2 % inhibition in SW620−c2orf68 cells were observed using the MTT assay. Flow cytometry analysis indicates that the cell apoptosis rate was 21.42 % in SW480−c2orf68 cells and 17.78 % in SW620−c2orf68 cells, whereas the percentage of G1 phase cells was 61.8 and 58.6 % in SW480−c2orf68 and SW620−c2orf68 cells, respectively. In addition, the mRNA expression of set and Bax was up-regulated after c2orf68 interfered in SW480−c2orf68 and SW620−c2orf68 cells, whereas that of Bcl-2, c-Myc, cyclinD1, caspase3 and pp2a was down-regulated. Consistent with the mRNA results, the protein expression of C2ORF68, PP2A and c-Myc was down-regulated, whereas that of SET was up-regulated. Our data thus suggest that c2orf68 promotes carcinogenesis through the regulation of mammalian target of rapamycin signaling pathway.

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Acknowledgments

This study was supported by the research funds from the Project of Sichuan Science and Technique (2014SZ0002-14).

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Authors and Affiliations

  1. Department of Anatomy, College of Basic and Forensic Medicine, Sichuan University, Chengdu, Sichuan, People’s Republic of China

    Xiaoxia Wen, Jianjun Zhu, Lei Dong & Yao Chen

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  1. Xiaoxia Wen
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  2. Jianjun Zhu
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  3. Lei Dong
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  4. Yao Chen
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Correspondence to Yao Chen.

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Wen, X., Zhu, J., Dong, L. et al. The role of c2orf68 and PI3K/Akt/mTOR pathway in human colorectal cancer. Med Oncol 31, 92 (2014). https://doi.org/10.1007/s12032-014-0092-7

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  • DOI: https://doi.org/10.1007/s12032-014-0092-7

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