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Hypoxia-induced PLOD2 regulates invasion and epithelial-mesenchymal transition in endometrial carcinoma cells

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Abstract

Background

Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) was induced in hypoxia and participated in cancer development. However, the role of PLOD2 in endometrial carcinoma remains unclear.

Objective

To explore the influences and regulation mechanism of PLOD2 in endometrial carcinoma under hypoxic condition.

Methods

The small interfering RNA (siRNA) targeting to PLOD2 and pcDNA3.1-PLPD2 were transfected to endometrial carcinoma cells to alter PLOD2 expression. Cell proliferation ability was determined by colony formation assay. Wound healing assay used to detect cell migration ability. Transwell invasion assay was used to detect cell invasion ability.

Results

PLOD2 and Hypoxia-inducible factor-1α (HIF-1α) were induced by hypoxia. Down-regulation of PLOD2 did not affect endometrial carcinoma cell proliferation ability, while inhibited cell migration, invasion under hypoxic condition. Besides, down-regulation of PLOD2 increased the levels of γ-catenin and E-cadherin and decreased levels of Fibronectin and Snail under hypoxic condition. Down-regulation of PLOD2 also inactivated Src and phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) signaling under hypoxic condition. The promoting effects of PLOD2 overexpression on migration, invasion and epithelial-mesenchymal transition (EMT) of endometrial carcinoma cells were reversed by Akt inhibitor (MK2206) under hypoxic condition.

Conclusion

PLOD2 expression was increased in endometrial carcinoma cells under hypoxic condition. PLOD2 modulated migration, invasion, and EMT of endometrial carcinoma cells via PI3K/Akt signaling. PLOD2 may be a potential therapeutic target for endometrial carcinoma.

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Availability of data and materials

All data generated or analyzed during this study are included in this published article.

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Funding

This work was supported by the National Natural Science Foundation (Grant nos. 81860462, 81460227).

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Author notes

  1. Junhui Wan and Junli Qin contributed equally to the work.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, 1st Affiliated Hospital of Nanchang University, 17# Yongwai Zheng Street, Nanchang City, Jiangxi Province, 330006, China

    Junhui Wan, Junli Qin & Chunhua Tu

  2. Department of Obstetrics and Gynecology, Medical College of Nanchang University, Nanchang City, Jiangxi Province, 330006, China

    Qinyue Cao, Ping Hu & Chunmei Zhong

Authors
  1. Junhui Wan
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  2. Junli Qin
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  3. Qinyue Cao
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  4. Ping Hu
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  5. Chunmei Zhong
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  6. Chunhua Tu
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Contributions

JHW, JLQ and CHT conceived and designed the experiments,QYC and PH analyzed and interpreted the results of the experiments, CMZ performed the experiments.

Corresponding author

Correspondence to Chunhua Tu.

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Conflict of interest

Junhui Wan, Junli Qin, Qinyue Cao, Ping Hu, Chunmei Zhong, and Chunhua Tu declare that they have no conflict of interest.

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The animal use protocol listed below has been reviewed and approved by the Animal Ethical and Welfare Committee.

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Not Applicable.

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Wan, J., Qin, J., Cao, Q. et al. Hypoxia-induced PLOD2 regulates invasion and epithelial-mesenchymal transition in endometrial carcinoma cells. Genes Genom 42, 317–324 (2020). https://doi.org/10.1007/s13258-019-00901-y

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  • DOI: https://doi.org/10.1007/s13258-019-00901-y

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