2. Academic Validation
  3. EIF4A3-mediated circ_0042881 activates the RAS pathway via miR-217/SOS1 axis to facilitate breast cancer progression

EIF4A3-mediated circ_0042881 activates the RAS pathway via miR-217/SOS1 axis to facilitate breast cancer progression

  • Cell Death Dis. 2023 Aug 25;14(8):559. doi: 10.1038/s41419-023-06085-4.
Chenxi Ju # 1,  Mingxia Zhou # 2,  Dan Du # 1,  Chang Wang 1,  Jieqiong Yao 3,  Hongle Li 4,  Yang Luo 5 6,  Fucheng He 7,  Jing He 8
Affiliations

Affiliations

  • 1 Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
  • 2 Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
  • 3 Department of Pathology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450014, China.
  • 4 Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, China.
  • 5 Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. luoy@cqu.edu.cn.
  • 6 Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University, Chongqing, 400044, China. luoy@cqu.edu.cn.
  • 7 Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. hefucheng@zzu.edu.cn.
  • 8 Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. hejing92921@163.com.
  • # Contributed equally.
PMID: 37626035 DOI: 10.1038/s41419-023-06085-4
Abstract

Breast Cancer (BC) is one of the most frequent cancer-related deaths in women worldwide. Studies have shown the potential impact of circRNAs in multiple human tumorigeneses. Research on the vital signaling pathways and therapeutic targets of circRNAs is indispensable. Here, we aimed to investigate the clinical implications and underlying mechanisms of circ_0042881 in BC. RT-qPCR validated circ_0042881 was notably elevated in BC tissues and plasma, and closely associated with BC clinicopathological features. Functionally, circ_0042881 significantly accelerated the proliferation, migration, and invasion of BC cells in vitro and tumor growth and metastasis in vivo. Mechanistically, circ_0042881 promoted BC progression by sponging miR-217 to relieve its inhibition effect in son of sevenless 1 (SOS1), which further activated Ras protein and initiated downstream signaling cascades, including MEK/ERK pathway and PI3K/Akt pathway. We also demonstrated that treatment of BAY-293, an inhibitor of SOS1 and Ras interaction, attenuated BC progression induced by circ_0042881 overexpression. Furthermore, Eukaryotic initiation factor 4A-III (EIF4A3) could facilitate circ_0042881 circularization. Altogether, we proposed a novel signaling network in which circ_0042881, induced by EIF4A3, influences the process of BC tumorigenesis and metastasis by miR-217/SOS1 axis.

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