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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1455909
This article is part of the Research Topic The Role of Circular RNAs and MicroRNAs in Non-Small Cell Lung Cancer: From Mechanisms to Therapeutic Potential View all articles

circUBE2G1 Interacts with hnRNPU to Promote VEGF-C-Mediated Lymph Node Metastasis of Lung Adenocarcinoma

Provisionally accepted
Yuting Li Yuting Li 1Hui Chen Hui Chen 2,3*Yue Zhao Yue Zhao 4*Qilu Yan Qilu Yan 1*Lulu Chen Lulu Chen 1*Qibin Song Qibin Song 1*
  • 1 Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
  • 2 Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
  • 3 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, State Key Laboratory of Oncology in South China, Guangzhou, China
  • 4 Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

The final, formatted version of the article will be published soon.

    Background: Patients with lymph node(LN)metastasis-positive Lung adenocarcinoma (LUAD)suffer from a significantly reduced five-year survival rate. Increasing evidence indicates circular RNAs(circRNAs)play crucial roles in regulating cancer progression. However, the specific regulatory mechanisms of circRNAs in the LN metastasis of LUAD have not been fully explored.Methods: GEO datasets and sequence analysis were applied for the identification of differentially expressed circRNAs between LUAD tissues and adjacent normal tissues. In vitro and in vivo experiments were performed to evaluate the function of circUBE2G1. The interaction between circUBE2G1 and VEGF-C was determined by RNA pulldown, ChIP, ChIRP and luciferase assays.In this study, we identified a novel circRNA, circUBE2G1 (hsa_circ_0041555), which is upregulated in LUAD and positively correlated with LN metastasis in patients with LUAD. Functionally, overexpression of circUBE2G1 promotes lymphangiogenesis and LN metastasis of LUAD both in vitro and in vivo. Mechanistically, circUBE2G1 activates the transcription of vascular endothelial growth factor C (VEGF-C) by recruiting hnRNPU to enhance H3K27ac on the VEGF-C promoter, thereby facilitating lymphangiogenesis and LN metastasis in LUAD.Our findings offer new insights into the mechanisms behind circRNA-mediated LN metastasis in LUAD and suggest that circUBE2G1 may serve as a potential therapeutic target for LN metastasis in LUAD.

    Keywords: Lung Adenocarcinoma, Vascular Endothelial Growth Factor C, Lymphangiogenesis, lymph node metastasis, circular RNAs

    Received: 27 Jun 2024; Accepted: 08 Nov 2024.

    Copyright: © 2024 Li, Chen, Zhao, Yan, Chen and Song. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Hui Chen, Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
    Yue Zhao, Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
    Qilu Yan, Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
    Lulu Chen, Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
    Qibin Song, Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China

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