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LPA3 is a precise therapeutic target and potential biomarker for ovarian cancer

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Abstract

Current studies have demonstrated that significant increased LPA levels to be observed in ascites in patients with ovarian cancer. Although several studies have shown that Lysophosphatidic acid (LPA) related to the progression of ovarian cancer, which LPA receptors (LPARs) and G-coupled protein subtypes mediated in LPA actions have not been clearly elucidated. This study aimed to clarify the roles of LPA and it is subtype-specific LPARs mediating mechanisms in ovarian cancer integrated using bioinformatic analysis and biological experimental approaches. The big data analysis shown that LPA3 was the only differentially expressed LPA receptor among the six LPARs in ovarian cancer and further verified in immunohistochemistry of tissue microarrays. Also found that LPA3 was also highly expressed in ovarian cancer tissue and ovarian cancer cells. Importantly, LPA significantly promoted the proliferation and migration of LPA3-overexpressing ovarian cancer cells, while the LPA-induced actions blocked by Ki16425, a LPAR1/3 antagonist treated, and LPA3-shRNA transfected. In vivo study indicated that the LPA3-overexpressing cell-derived tumors metastasis, tumors volume, and tumors mass were apparently increased in xenografted nude mice. In addition, we also observed that LPA3 was differential high expression in ovarian cancer tissue of the patients. Our studies further confirmed the LPA3/Gi/MAPKs/NF-κB signals were involved in LPA-induced oncogenic actions in ovarian cancer cells. Our findings indicated that the LPA3 might be a novel precise therapeutic target and potential biomarker for ovarian cancer.

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Data availability

All data included in this study are available upon request by contact with the corresponding author.

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Acknowledgements

We are grateful to Prof. Fumikazu Okajima at Gunma University for a generous gift of the Ki16425.

Funding

This work was supported by the National Natural Science Foundation of China (No. 31860253, 31971219).

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Authors and Affiliations

  1. The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia, China

    Pengfei Zhao, Qingru Yun, Aodungerile Li, Rong Li, Yali Yan, Yuewu Wang, Hongju Sun & Alatangaole Damirin

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  1. Pengfei Zhao
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  2. Qingru Yun
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  3. Aodungerile Li
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  4. Rong Li
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  5. Yali Yan
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  6. Yuewu Wang
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  7. Hongju Sun
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  8. Alatangaole Damirin
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Contributions

AD and PZ contributed to design the study. PZ, QY, AL, RL, and YY performed the experiment and collected data. YW performed the animal experiments. PZ and HS analyzed the data and wrote the manuscript. AD revised manuscript critically for important intellectual content and final approval of the version submitted for publication. All the authors approved the final manuscript.

Corresponding authors

Correspondence to Hongju Sun or Alatangaole Damirin.

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The authors report no conflict of interest for this work.

Ethical approval

All experiments used in this study were performed with ethical standards that the Declaration of Helsinki and national and international guidelines. This investigation was reviewed and approved by the Institutional Animal Care and Use Committee of Inner Mongolia University (Approval Number 2020001).

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Zhao, P., Yun, Q., Li, A. et al. LPA3 is a precise therapeutic target and potential biomarker for ovarian cancer. Med Oncol 39, 17 (2022). https://doi.org/10.1007/s12032-021-01616-5

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  • DOI: https://doi.org/10.1007/s12032-021-01616-5

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