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A Circular RNA, hsa_circ_0018180 (circPARD3), Triggers Glycolysis and Promotes Malignancy of Head and Neck Squamous Cell Carcinoma Through the miR-5194/ENO1 Axis

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Abstract

Emerging evidence has demonstrated the pivotal roles of circular RNAs (circRNAs) in the modulation of malignancy and pathological progression among multiple human cancers. Glucose metabolism reprogramming is a widely identified characteristic for contributing to facilitate tumorigenesis. Nonetheless, their contributions to head and neck squamous cell carcinoma (HNSCC) cell glycolysis remain to be further elucidated. Herein, we aim to investigate the role of circRNA, hsa_circ_0018180 (also named as circPARD3) in HNSCC. Expression patterns of circPARD3 in HNSCC tissues and different cell lines were determined by qRT-PCR assay, as well as its correlation with the prognosis of survival. CCK-8, EdU incorporation, and transwell assays were carried out to assess the cell viability, proliferation, migration, and invasion, respectively. Glucose uptake and lactate production were evaluated by preforming glycolysis. Mechanistically, the circPARD3/miR-5194/ENO1 axis was verified by RNA immunoprecipitation (RIP) and luciferase reporter assays. Western blot analysis was employed to measure the epithelial-mesenchymal transition (EMT)-associated biomarkers. Upregulated circPARD3 observed in HNSCC tissues and cell lines indicated the poor prognosis of patients. Stable knockdown of circPARD3 dramatically exerted the suppressive effects on cell viability, proliferation, migration, and invasion, as well as glucose uptake and lactate production. Mechanistically, circPARD3 harbored miR-5194, serving as a miRNA sponge, thereby increasing ENO1 expression. Moreover, ENO1 evidently reversed miR-5194-mediated attenuated malignant behaviors. Collectively, our study identified an oncogenic role of circPARD3 in HNSCC through a novel machinery of circPARD3/miR-5194/ENO1 and provided a promising therapeutic target for HNSCC.

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Funding

This study was supported by the Natural Science Foundation of China (Nos. 82073006, 81902757, 82002757).

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Authors and Affiliations

  1. Department of Maxillofacial and Otorhinolaryngology Oncology and Department of Head and Neck Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer & Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, West Huan-Hu Rd, Ti Yuan Bei, Hexi District, Tianjin, 300060, People’s Republic of China

    Jing-Tao Luo, Ya-fei Wang, Yun Wang, Chun-Li Wang, Ruo-Yan Liu & Ze Zhang

Authors
  1. Jing-Tao Luo
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  2. Ya-fei Wang
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  3. Yun Wang
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  4. Chun-Li Wang
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  5. Ruo-Yan Liu
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  6. Ze Zhang
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Contributions

J-TL: Conceptualization; Writing-original draft; Methodology; Formal analysis; Y-fW: Supervision; Validation; YW, R-YL: Data curation; Resources; C-LW: Investigation; ZZ: Funding acquisition; Project administration; Writing-review & editing. All authors have read and approved the final version of this manuscript to be published.

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Correspondence to Jing-Tao Luo or Ze Zhang.

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The authors declare that there are no conflicts of interest.

Ethical Approval

This study was approved by the Ethics Committee of Tianjin Cancer Hospital in accordance to the Declaration of Helsinki. All experiments involving the clinical patients were conducted on the order with provisions of the Declaration of Helsinki and Good Clinical Practice guidelines.

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10528_2022_10253_MOESM1_ESM.tif

Supplementary file1 Figure S1. Verification of circPARD3/miR-5194/ENO1 axis. (A) circPARD3 in the HN30 and SCC-25 cell lysates was pulled down and enriched with circPARD3 specific probe and then assessed by qRT-PCR. (B and C) The relative five candidate miRNAs in the HN30 and SCC-25 cell lysates were measured by qRT-PCR. (D) The biotinylated miR-5193 was transfected into HN30 and SCC-25 cells, and the enrichment of circpARD3 was quantified by qRT-PCR. (E) Dual-luciferase reporter assay in 293T cells was used to validate the binding relationship of circPARD3 and miR-5194. (F) Dual-luciferase reporter gene system in 293T cells for examining the binding sites between miR-5194 and ENO1. Data were representative images or were expressed as the mean ± SD of n = 3 experiments. *, P < 0.05, **, P < 0.01, ***, P < 0.001. (TIF 338 kb)

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Luo, JT., Wang, Yf., Wang, Y. et al. A Circular RNA, hsa_circ_0018180 (circPARD3), Triggers Glycolysis and Promotes Malignancy of Head and Neck Squamous Cell Carcinoma Through the miR-5194/ENO1 Axis. Biochem Genet 61, 316–335 (2023). https://doi.org/10.1007/s10528-022-10253-0

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