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Checkpoint kinase 1 is negatively regulated by miR-497 in hepatocellular carcinoma

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Abstract

Checkpoint kinase 1 (CHEK1) is an evolutionarily conserved Ser/Thr kinase, which mediates cell-cycle arrest after DNA damage, and we previously reported that CHEK1 was overexpressed and associated with poor prognosis in hepatocellular carcinoma (HCC), indicating it was oncogenic gene. In this study, we aimed to elucidate the mechanism of CHEK1 overexpression in HCC. We first verified the upregulated CHEK1 by qRT-PCR and western blot in 30 HCC samples compared with corresponding non-tumor liver tissues. In silico analysis showed that CHEK1 was a candidate target of miR-497, which was previously found to be downregulated in HCC by us. To test whether miR-497 could bind to 3′untranslated region (3′UTR) of CHEK1, luciferase reporter assay was conducted. The result revealed that miR-497 could bind to the 3′untranslated region (3′UTR) of CHEK1 mRNA. Western blot showed that ectopic expression of miR-497 suppressed the CHEK1 expression and inhibition of miR-497 led to significant upregulation of CHEK1. Finally, miR-497 expression was measured in the same 30 HCC samples, and the correlation between miR-497 and CHEK1 was analyzed. The results indicated that miR-497 was downregulated in HCC and had a significant negative correlation with CHEK1. Taken together, these results demonstrated that CHEK1 was negatively regulated by miR-497, and the overexpressed CHEK1 was resulted from the downregulated miR-497 in HCC, which provided a potential molecular target for HCC therapy.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No: 30973397 to H-Y W).

Conflict of interest

The authors declare no conflicts of interest in this work.

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Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong Province, China

    Yin Xie, Rong-Rong Wei, Mei-Yin Zhang & Hui-Yun Wang

  2. Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong Province, China

    Yin Xie, Rong-Rong Wei, Mei-Yin Zhang & Hui-Yun Wang

  3. Sino-American Cancer Research Institute, Guangdong Medical College, Dongguan, 523808, China

    Guo-Liang Huang

  4. Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong Province, China

    Yun-Fei Yuan

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  1. Yin Xie
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  2. Rong-Rong Wei
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  3. Guo-Liang Huang
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  4. Mei-Yin Zhang
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Correspondence to Hui-Yun Wang.

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Xie, Y., Wei, RR., Huang, GL. et al. Checkpoint kinase 1 is negatively regulated by miR-497 in hepatocellular carcinoma. Med Oncol 31, 844 (2014). https://doi.org/10.1007/s12032-014-0844-4

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  • DOI: https://doi.org/10.1007/s12032-014-0844-4

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