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Hypoxia-induced PPFIA4 accelerates the progression of ovarian cancer through glucose metabolic reprogramming

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Abstract

Dysregulated glycolysis promotes growth and metastasis, which is one of the metabolic characteristics of ovarian cancer. Based on bioinformatics analysis, liprin-alpha-4 (PPFIA4) is a gene associated with hypoxia, and we aimed to investigate the potential mechanism of PPFIA4 during the reprogramming of glucose metabolism in ovarian cancer cells. Currently, the cell viability of ovarian cancer cells under the hypoxia treatment was evaluated by CCK-8 assay, and cell migration and invasion were measured by transwell assay and western blot. The effects of hypoxia treatment on glucose uptake, lactate production, extracellular acidification rate (ECAR), adenosine triphosphate (ATP), reactive oxygen species (ROS), Nicotinamide adenine dinucleotide phosphate (NADPH) and its oxidized form NADP + , and oxygen consumption rate (OCR) in ovarian cancer cells were examined. Then PPFIA4 was identified through bioinformatic analysis, and the regulatory effects of PPFIA4 on glucose metabolic reprogramming. Our data suggested that hypoxia enhanced the migration and invasion ability of ovarian cancer cells in vitro, and promoted the glucose metabolic reprogramming of ovarian cancer cells. Ovarian cancer cell viability, migration, and invasion were inhibited after PPFIA4 knockdown. Inhibition of PPFIA4 inhibited hypoxic-induced glucose metabolic reprogramming in ovarian cancer cells. In addition, PPFIA4 was found to bind to hypoxia-inducible factor 1alpha (HIF1A), and HIF1A prominently induced PPFIA4 expression. Collectively, HIF1A mediated upregulation of PPFIA4 and promoted reprogramming of glucose metabolism in ovarian cancer cells. Therefore, PPFIA4 may be a therapeutic target for ovarian cancer intervention.

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Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the Haiyan Scientific Research Fund Youth Project of Harbin Medical University Cancer Hospital (Grant Number JJQN2019-03); Heilongjiang Natural Science Foundation (Grant Number YQ2019H025).

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  1. Department of Gynecology Oncology, Harbin Medical University Cancer Hospital, Nangang District, Harbin City, 150081, Heilongjiang Province, China

    Shu Tan, Ye Xu, Yue Zhao & Ge Lou

  2. Nangang District of Heilongjiang Provincial Hospital, Harbin, China

    Hao Yu

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All authors participated in the design, interpretation of the studies and analysis of the data and review of the manuscript. ST drafted the work and revised it critically for important intellectual content; HY and YX were responsible for the acquisition and analysis of data for the work; YZ was responsible for the interpretation of data for the work; GL made substantial contributions to the conception or design of the work.

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Correspondence to Ge Lou.

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Tan, S., Yu, H., Xu, Y. et al. Hypoxia-induced PPFIA4 accelerates the progression of ovarian cancer through glucose metabolic reprogramming. Med Oncol 40, 272 (2023). https://doi.org/10.1007/s12032-023-02144-0

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