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Downregulation of HOXA11 enhances endometrial cancer malignancy and cisplatin resistance via activating PTEN/AKT signaling pathway

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Abstract

Purpose

Endometrial cancer is the most common malignant tumor of female genital system worldwide. Homeobox A11 (HOXA11) is an evolutionarily conserved Homeobox gene closely implicated in carcinogenesis. However, the mechanisms of HOXA11 in the progression and cisplatin resistance of endometrial cancer remain unclear.

Methods

The expression of HOXA11 was analyzed based on 548 endometrial cancer and 35 control tissues from The Cancer Genome Atlas (TCGA) database. Transwell assay was performed to investigate the effect of HOXA11 on endometrial cell migration and invasion. TUNEL staining was carried out to assay the role of HOXA11 in endometrial cell apoptosis. Western blot was employed to detect the protein levels of B cell lymphoma-2 (Bcl-2), Bcl-2 associated X (Bax), cleaved caspase-3, matrix metalloproteinase-2/9 (MMP/9), phosphatase and tensin homolog (PTEN), protein kinase B (AKT) and p-AKT.

Results

TCGA data showed that HOXA11 expression was significantly down-regulated in endometrial cancer tissue samples. The overexpression of HOXA11 promoted the apoptosis, but inhibited the proliferation, migration and invasion of endometrial cancer cells. HOXA11 knockdown with small interfering RNA (siRNA) considerably repressed cell apoptosis, while promoted cell proliferation, migration, and invasion through PTEN/AKT signaling pathway. Interestingly, HOXA11 was lowly expressed in Ishikawa cells treated with cisplatin. In addition, HOXA11 knockdown increased the resistance of endometrial cancer to cisplatin through activating PTEN/AKT signaling pathway.

Conclusion

Low HOXA11 expression may promote the proliferation, migration, invasion of endometrial cancer cells, and increase their resistance to cisplatin through activating PTEN/AKT pathway.

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Data availability

The datasets used during the present study are available from the corresponding authors upon reasonable request.

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Funding

The present research was supported by the National Natural Science Foundation of China (NO.81701516).

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Changzhou Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Changzhou, 213000, Jiangsu, China

    C. Kong, Y. Li, P. Xue & L. Chen

  2. Department of Gynecology and Obstetrics, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China

    Z. Zhu

Authors
  1. C. Kong
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  2. Z. Zhu
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  3. Y. Li
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  4. P. Xue
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  5. L. Chen
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Contributions

CCK was responsible for the conception and design of the study. ZHZ and YL were responsible for acquisition of data. PPX and CCK drafted the manuscript. LC performed the Formal analysis. CCK revised and commented the draft, and all authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to C. Kong.

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There is no conflict of interest in this manuscript.

Ethical approval

The RNA sequencing data of Human endometrial cancer obtained from TCGA dataset. This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Kong, C., Zhu, Z., Li, Y. et al. Downregulation of HOXA11 enhances endometrial cancer malignancy and cisplatin resistance via activating PTEN/AKT signaling pathway. Clin Transl Oncol 23, 1334–1341 (2021). https://doi.org/10.1007/s12094-020-02520-6

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  • DOI: https://doi.org/10.1007/s12094-020-02520-6

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