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ERCC6L that is up-regulated in high grade of renal cell carcinoma enhances cell viability in vitro and promotes tumor growth in vivo potentially through modulating MAPK signalling pathway

Cancer Gene Therapy volume 26, pages 323–333 (2019)Cite this article

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A Correction to this article was published on 28 January 2022

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Abstract

Renal cell carcinoma (RCC), which is one of the most diagnosed urological malignancies worldwide, is usually associated with abnormality in both genetic and cellular processes. In the present study, through analyzing The Cancer Genome Atlas (TCGA) dataset, we screened out ERCC6L as a candidate gene that is potentially related to the development of RCC based on its increased expression in ccRCC tissues compared with normal kidney tissues as well as its possible relevance to cancer prognosis. Evidence indicates that ERCC6L is an indispensable component of mammalian cell mitosis, while it fails to disclose the role of ERCC6L in tumorigenesis. By using RT-PCR, it was confirmed that the mRNA expression of ERCC6L was upregulated in RCC tissues as compared to normal controls in 28 pared samples. In addition, the immunohistochemistry study in a tissue microarray (TMA) containing 150 ccRCC samples showed that the staining score of ERCC6L was positively correlated with the Fuhrman grade of cancers. Next, when the expression of ERCC6L was lowered by specific shRNA, the cell viability was significantly inhibited in 786-O and Caki-1 cells, while the apoptosis was induced accordingly. At the same time, RCC cells those were transfected with shRNA targeting to ERCC6L grew significantly slower than parental cells in immunodeficient mice. These results consistently suggest that ERCC6L may play a role in regulating the cell viability of RCC both in vitro and in vivo. Further, gene expression microarray analysis followed by the validating western blot after knocking down ERCC6L expression in 786-O cells highlighted the involvement of MAPK signaling pathway in regulation of ERCC6L on cellular process of RCC. In conclusion, the present study suggests a likely promoting role of ERCC6L on the development of RCC. Thus, further study to explore the potential utility of ERCC6L as a novel therapeutic target of RCC is clearly needed.

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Acknowledgements

Funding

This study is partially supported by the National Natural Science Foundation of China (grant nos. 81372766 and 81572532), and the Liaoning “Climbing” scholarship.

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Authors and Affiliations

  1. Department of Urology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, 110042, China

    Gejun Zhang, Zi Yu, Shui Fu, Chengcheng Lv, Qingzhuo Dong, Cheng Fu & Yu Zeng

  2. Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, China

    Gejun Zhang, Zi Yu & Chuize Kong

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  1. Gejun Zhang
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Correspondence to Yu Zeng.

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Additional information

The original online version of this article was revised: The authors wish to notify the readers of the following change: In “Depletion of ERCC6L induces apoptosis” section, in the sentence “The percentages of apoptotic cells in the sh-ERCC6L and sh-Ctrl groups were 8.33% and 3.80% respectively (P < 0.01) and 9.29% and 3.94% respectively (P < 0.01) in the 786-O cells and Caki-1 cells (Fig. 2G)”; the percentages of apoptotic cell in the sh-ERCC6L and sh-Ctrl groups in the 786-0 cells should be “8.46% and 5.02%” and the P value should be “P < 0.05”. Figure 2G, left panel, the above two graphs of flow cytometry of 786-0 cells should be replaced by the correct graphs, and in the right panel, the left two columns representing apoptotic cells of 786-0 cells should be replaced by those representing the correct number of apoptotic cells of 786-0 cells. Finally, at the end of “Fig. 2” legend, “*P < 0.05” should be added before the last sentence “P < 0.01”.

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Zhang, G., Yu, Z., Fu, S. et al. ERCC6L that is up-regulated in high grade of renal cell carcinoma enhances cell viability in vitro and promotes tumor growth in vivo potentially through modulating MAPK signalling pathway. Cancer Gene Ther 26, 323–333 (2019). https://doi.org/10.1038/s41417-018-0064-8

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