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Hsa_circ_0014606 Derived from Exosomes Promotes Gastric Carcinoma Tumorigenesis and Proliferation by Sponging miR-514b-3p to Upregulate HNRNPC

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Abstract

Gastric cancer is a common malignant tumor, and due to its insidious onset and limited screening methods, most patients are diagnosed with advanced disease and have a poor prognosis. The circRNA in exosomes has an essential role in cancer diagnosis and treatment. However, the part of hsa_circ_0014606 within exosomes in gastric cancer progression is unclear. Firstly, we extracted exosomes from the serum of gastric cancer patients and healthy individuals by ultracentrifugation and analyzed the expression of hsa_circ_0014606 in both exosomes; then knocked down hsa_circ_0014606 in vivo and in vitro, respectively, to observe its effect on the physiological function of gastric cancer cells; finally, we used bioinformatics to screen hsa_circ_0014606 targeting miRNAs and mRNAs, and experiments were performed to verify the interrelationship between the three. The results showed that the level of hsa_circ_0014606 in the serum exosomes of gastric cancer patients was significantly higher than that of the healthy population. The knockdown of hsa_circ_0014606 slowed the proliferation of gastric cancer cells, significantly reduced migration and invasion ability, accelerated apoptosis, and reduced tumor size in mice. In addition, the expression of hsa_circ_0014606 was negatively correlated with the expression of miR-514b-3p and positively correlated with the expression of heterogeneous nuclear ribonucleoprotein C (HNRNPC). In conclusion, hsa_circ_0014606 exerted a pro-cancer effect indirectly through miR-514b-3p targeting gene HNRNPC, and this study provides a new potential target for treating gastric cancer.

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Data Availability

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

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Funding

This work was supported by a grant from “1 + X” program for clinical competency enhancement–interdisciplinary innovation project, the Second Hospital of Dalian Medical University (2022JCXKYB02).

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Author notes

  1. Tao Jiang and Lingling Xu contributed equally for this work.

Authors and Affiliations

  1. Department of Otolaryngology, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China

    Tao Jiang & Rui Li

  2. Department of Medical Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China

    Lingling Xu, Xiaona Qu, Ye Cheng & Hongmei He

Authors
  1. Tao Jiang
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  2. Lingling Xu
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  3. Xiaona Qu
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  4. Rui Li
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  6. Hongmei He
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Contributions

JT, XL, and HH conceived and designed the experiments. JT, XL, QX, LR, and CY performed the experiments and contributed reagents/materials/analysis tools. JT, XL, and HH wrote the paper. All authors have read and approved the manuscript. JT is the first author; XL is the co-first author; HH is the corresponding author.

Corresponding author

Correspondence to Hongmei He.

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All experiments were approved by the Second Hospital of Dalian Medical University, Dalian, China. And all experiments were performed in accordance with relevant guidelines and regulations.

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Jiang, T., Xu, L., Qu, X. et al. Hsa_circ_0014606 Derived from Exosomes Promotes Gastric Carcinoma Tumorigenesis and Proliferation by Sponging miR-514b-3p to Upregulate HNRNPC. Dig Dis Sci 69, 811–820 (2024). https://doi.org/10.1007/s10620-023-08254-z

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  • DOI: https://doi.org/10.1007/s10620-023-08254-z

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