2. Academic Validation
  3. CircBIRC6 facilitates the malignant progression via miR-488/GRIN2D-mediated CAV1-autophagy signal axis in gastric cancer

CircBIRC6 facilitates the malignant progression via miR-488/GRIN2D-mediated CAV1-autophagy signal axis in gastric cancer

  • Pharmacol Res. 2024 Mar 2:202:107127. doi: 10.1016/j.phrs.2024.107127.
Zhiyuan Tang 1,  Jieying Li 1,  Bing Lu 1,  Xiaojing Zhang 1,  Lei Yang 1,  Yue Qi 1,  Sutian Jiang 1,  Qianqian Wu 1,  Yingjing Wang 1,  Tong Cheng 1,  Manyu Xu 1,  Pingping Sun 1,  Xudong Wang 2,  Kai Miao 3,  Han Wu 4,  Jianfei Huang 5
Affiliations

Affiliations

  • 1 Department of Clinical Biobank, Department of Pharmacy, Affiliated Hospital of Nantong University & Department of Pathology, Medical School of Nantong University, Nantong 226001, China.
  • 2 Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong 226001, China.
  • 3 MOE Frontier Science Centre for Precision Oncology, University of Macau, Macau. Electronic address: [email protected].
  • 4 Department of General Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China. Electronic address: [email protected].
  • 5 Department of Clinical Biobank, Department of Pharmacy, Affiliated Hospital of Nantong University & Department of Pathology, Medical School of Nantong University, Nantong 226001, China. Electronic address: [email protected].
PMID: 38438090 DOI: 10.1016/j.phrs.2024.107127
Abstract

Circular RNAs (circRNAs) represent a novel class of non-coding RNAs that play significant roles in tumorigenesis and tumor progression. High-throughput sequencing of gastric Cancer (GC) tissues has identified circRNA BIRC6 (circBIRC6) as a potential circRNA derived from the BIRC6 gene, exhibiting significant upregulation in GC tissues. The expression of circBIRC6 is notably elevated in GC patients. Functionally, it acts as a molecular Sponge for miR-488, consequently upregulating GRIN2D expression and promoting GC proliferation, migration, and invasion. Moreover, overexpression of circBIRC6 leads to increased GRIN2D expression, which in turn enhances caveolin-1 (CAV1) expression, resulting in Autophagy deficiency due to miR-488 sequestration. This cascade of events significantly influences tumorigenesis in vivo. Our findings collectively illustrate that the CircBIRC6-miR-488-GRIN2D axis fosters CAV1 expression in GC cells, thereby reducing Autophagy levels. Both circBIRC6 and GRIN2D emerge as potential targets for treatment and independent prognostic factors for GC patients.

Keywords

CircBIRC6; Gastric cancer; Grin2D.

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