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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Breast Cancer
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1476731
This article is part of the Research Topic Non-coding RNAs in Breast Cancer - Volume II View all 12 articles

EIF4A3-induced circ_0022382 promotes breast cancer cell progression through the let-7a-5p/PI3K/AKT/mTOR signaling pathway and SLC7A11 axis

Provisionally accepted
Wei Liu Wei Liu 1Jun Zhang Jun Zhang 2*Jiawen Zhang Jiawen Zhang 1*Yu Ye Yu Ye 1*Jianqin Zhu Jianqin Zhu 1*Qiwen Yu Qiwen Yu 1*Tao Li Tao Li 3Xiaochun Sun Xiaochun Sun 1*Huabiao Chen Huabiao Chen 3*
  • 1 Jiangsu University, Zhenjiang, China
  • 2 Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, China
  • 3 Ningbo University, Ningbo, Zhejiang Province, China

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

    Abstract: Breast cancer is one of the most common cancers in women and poses a serious threat to women's health. In this paper, we screened out circ_0022382 in breast cancer by differential analysis of breast cancer and adjacent tissues in the Gene Expression Omnibus database. The high expression of circ_0022382 in breast cancer cell lines MDA-MB-231, MCF-7 as well as breast cancer tissues was confirmed by quantitative real-time PCR (qRT-PCR). Cell Counting Kit-8 experiment and migration assay showed that the proliferative and migratory capacity in MDA-MB-231 and MCF-7 cells transfected with si-circ_0022382 were significantly decreased. In terms of regulatory mechanisms, qRT-PCR and dual luciferase reporter assay showed that circ_0022382 could act as a sponge of let-7a-5p. Kyoto Encyclopedia of Genes and Genomes enrichment analysis and cell immunofluorescence showed that circ_0022382 could activate PI3K/AKT/mTOR signaling pathway and SLC7A11 by sponging let-7a-5p. Clone formation assay and scratch wound healing experiment showed that dithiothreitol (cystine inhibitor) could rescue the proliferative and migratory capacity of MDA-MB-231 and MCF-7 cells transfected with si-circ_0022382, whose concentration of glucose and NADPH also declined, which confirmed the occurrence of disulfidptosis. In addition, qRT-PCR and RNA immunoprecipitation showed that EIF4A3 could promote the expression of circ_0022382 in MDA-MB-231 and MCF-7. In conclusion, EIF4A3 promotes the expression of circ_0022382, increasing circ_0022382 could activate PI3K/AKT/mTOR signaling pathway and SLC7A11 by sponging let-7a-5p, while knockdown of circ_0022382 could inhibit the proliferation and migration of breast cancer cells, and meanwhile contribute to the occurrence of disulfidptosis. Therefore, circ_0022382 and its related molecules may be effective targets for diagnosis or targeted therapy of breast cancer.

    Keywords: breast cancer, circ_0022382, Let-7a-5p, PI3K/Akt/mTOR signaling pathway, SLC7A11, disulfidptosis, EIF4A3

    Received: 06 Aug 2024; Accepted: 16 Dec 2024.

    Copyright: © 2024 Liu, Zhang, Zhang, Ye, Zhu, Yu, Li, Sun and Chen. 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:
    Jun Zhang, Affiliated Hospital of Yangzhou University, Yangzhou, 225001, Jiangsu Province, China
    Jiawen Zhang, Jiangsu University, Zhenjiang, China
    Yu Ye, Jiangsu University, Zhenjiang, China
    Jianqin Zhu, Jiangsu University, Zhenjiang, China
    Qiwen Yu, Jiangsu University, Zhenjiang, China
    Xiaochun Sun, Jiangsu University, Zhenjiang, China
    Huabiao Chen, Ningbo University, Ningbo, 315211, Zhejiang Province, China

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