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Comprehensive analysis of the HOXA gene family identifies HOXA13 as a novel oncogenic gene in kidney renal clear cell carcinoma

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Objectives

Kidney renal clear cell carcinoma (KIRC) is one of the most common lethal cancers in the human urogenital system. As members of the Homeobox (HOX) family, Homeobox-A (HOXA) cluster genes have been reported to be involved in the development of many cancer types. However, the expression and clinical significance of HOXA genes in KIRC remain largely unknown.

Materials and methods

In this study, we comprehensively analyzed the mRNA expression and prognostic values of HOXA genes in KIRC using The Cancer Genome Atlas (TCGA) analysis databases online. Colony formation assay, flow cytometry and Western blot were used to detect cell proliferation, apoptosis, cell cycle, and protein level of the indicated gene.

Results

We found that the HOXA genes were differentially expressed in KIRC tissues when compared with normal tissues. The expression of HOXA4 and HOXA13 were significantly up-regulated, while HOXA7 and HOXA11 were down-regulated in KIRC. High mRNA levels of HOXA2, HOXA3 and HOXA13, and low level of HOXA7 predicted poor overall survival (OS) of KIRC patients. High mRNA level of HOXA13 further indicated a poor disease-free survival (DFS) of KIRC patients. Functionally, knockdown of HOXA13 significantly suppressed cell proliferation of KIRC in vitro, increased the protein level of p53 and decreased the protein level of cyclin D1 in KIRC cells. Over-expression of HOXA13 had the opposite effects on KIRC cells.

Conclusion

Collectively, our findings suggest that HOXA13 functions as a novel oncogene in KIRC and may be a potential biomarker for this malignancy.

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Acknowledgements

We thank all participants for this manuscript.

Funding

This work was supported by the Key Scientific Research Projects of Institutions of Higher Learning in Henan Province (20A310018), the Provincial Co-construction Project of Medical Science and Technology in Henan (SB201903032), the Key Scientific and Technological Project in Henan Province (182102310328).

Author information

Author notes

  1. Yuanbo Cui and Ming Yan contributed equally to this work.

Authors and Affiliations

  1. Department of Translational Medicine Center, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou, 450007, China

    Yuanbo Cui & Wei Cao

  2. School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, China

    Yuanbo Cui, Shanshan Ma & Fangxia Guan

  3. Basic Medical College, Zhengzhou University, Zhengzhou, 450001, China

    Ming Yan

  4. Department of Clinical Laboratory, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou, 450007, China

    Chunyan Zhang

  5. Department of Pathology, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou, 450007, China

    Jinhui Xue & Quanwu Zhang

Authors
  1. Yuanbo Cui
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  2. Ming Yan
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  4. Jinhui Xue
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  7. Fangxia Guan
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  8. Wei Cao
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Contributions

YBC conceived and designed this study and wrote the manuscript. MY, CYZ, JHX, QWZ and SSM participated in functional experiments and data analysis. WC and FXG assisted in the revision of the manuscript and sample collection. All authors read the manuscript and approved it for publication.

Corresponding authors

Correspondence to Yuanbo Cui, Fangxia Guan or Wei Cao.

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The authors have declared that they have no competing interests.

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This study was approved by the Ethics Committee of the Zhengzhou Central Hospital Affiliated to Zhengzhou University.

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Cui, Y., Yan, M., Zhang, C. et al. Comprehensive analysis of the HOXA gene family identifies HOXA13 as a novel oncogenic gene in kidney renal clear cell carcinoma. J Cancer Res Clin Oncol 146, 1993–2006 (2020). https://doi.org/10.1007/s00432-020-03259-x

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  • DOI: https://doi.org/10.1007/s00432-020-03259-x

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