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Abnormal activation of RFC3, A YAP1/TEAD downstream target, promotes gastric cancer progression

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Abstract

Background

Gastric cancer (GC) is a malignant tumor with a high mortality rate, and thus, it is necessary to explore molecular mechanisms underlying its progression. While replication factor C subunit 3 (RFC3) has been demonstrated to function as an oncogene in many cancers, its role in GC remains unclear.

Methods

Tumor tissues were collected from clinical GC patients, and the expression of RFC3 was analyzed. NCI-N87 and HGC-27 cells were infected with lentivirus sh-RFC3 to knock down RFC3 expression. RFC3 expression levels were determined, in addition to cell biological behaviors both in vitro and in vivo. The relationship between RFC3 and the YAP1/TEAD signaling pathway was detected by dual luciferase reporter assay.

Results

RFC3 was upregulated in GC tumor tissues. RFC3 knockdown inhibited cell proliferation, promoted cell apoptosis of GC cells, and suppressed cell migration and invasion. Moreover, depleted RFC3 suppressed tumor growth and metastasis in vivo. Mechanistically, the YAP1/TEAD axis activated RFC3 expression transcriptionally by binding to the RFC3 promoter.

Conclusions

RFC3 was transcriptional activated by the YAP1/TEAD signaling pathway, thus promoting GC progression. RFC3 may be a promising therapeutic target for GC.

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Data availability

The data used to support the findings of this study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Operating Room, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning, People’s Republic of China

    Zijun Guo

  2. Department of General Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, People’s Republic of China

    Lin Guo

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  1. Zijun Guo
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Contributions

All authors were involved in conceptualization and methodology; ZG performed formal analysis and investigation, and writing––original draft preparation; LG performed writing––review and editing, resources, and supervision.

Corresponding author

Correspondence to Lin Guo.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Ethics Committee of Shengjing Hospital of China Medical University with Approval No.2021PS644K for clinical specimen collection and Approval No. 2021PS645K for animal experiments.

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Guo, Z., Guo, L. Abnormal activation of RFC3, A YAP1/TEAD downstream target, promotes gastric cancer progression. Int J Clin Oncol 29, 442–455 (2024). https://doi.org/10.1007/s10147-024-02478-3

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  • DOI: https://doi.org/10.1007/s10147-024-02478-3

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