Shuguang Cao1, Beilei Fu1, Jing Cai2, Dingli Zhang1, Chenxing Wang1, Hao Wu3. 1. Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 West College Road, Wenzhou, 325000, Zhejiang, China. 2. Department of Comprehensive Medicine, Wenzhou Central Hospital Medical Group, the Affiliated Second Hospital of Shanghai University, Affiliated Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, 325000, China. 3. Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 West College Road, Wenzhou, 325000, Zhejiang, China. Wuhao0577@163.com.
Abstract
OBJECTIVE: Cisplatin (DDP)-based chemotherapy is commonly referred to as advanced gastric cancer (GC). The purpose of this study was to unravel whether Linc00852 from DDP-resistant tumor cell-derived exosomes (Exos) promotes DDP resistance of GC cells. METHODS: Reverse transcription quantitative polymerase chain reaction was used to detect the expression of Linc00852, miR-514a-5p, COMM domain protein 7 (COMMD7) mRNA, Bax mRNA, and Bcl-2 mRNA. Western blot was used to measure the expression of COMMD7 protein. The IC50 value of DDP is determined by MTT assay. The cell proliferation ability was measured by colony formation test. The apoptosis ability was measured by flow cytometry. The interaction between Linc00852, miR-514a-5p, and COMMD7 was confirmed by luciferase reporter gene assay and RNA pull-down assay. Xenograft tumor model was used to study the effect of Linc00852 on DDP resistance in vivo. RESULTS: Linc00852 was up-regulated in DDP-resistant GC cells and their secreted exosomes. Down-regulating Linc00852 facilitated the sensitivity of DDP-resistant GC cells to DDP. Linc00852 bound to miR-514a-5p and COMMD7 was a target of miR-514a-5p. Linc00852 could regulate COMMD7 expression via targeting miR-514a-5p. Exosomes from DDP-resistant GC cells enhanced the resistance of recipient GC cells to DDP via exosomal delivery of Linc00852. Depletion of Linc00852 repressed the growth and DDP resistance of GC cells in vivo. CONCLUSION: Linc00852 from DDP-resistant tumor cell-derived Exos regulates COMMD7 to promote drug resistance of GC cells through miR-514a-5p.
OBJECTIVE: Cisplatin (DDP)-based chemotherapy is commonly referred to as advanced gastric cancer (GC). The purpose of this study was to unravel whether Linc00852 from DDP-resistant tumor cell-derived exosomes (Exos) promotes DDP resistance of GC cells. METHODS: Reverse transcription quantitative polymerase chain reaction was used to detect the expression of Linc00852, miR-514a-5p, COMM domain protein 7 (COMMD7) mRNA, Bax mRNA, and Bcl-2 mRNA. Western blot was used to measure the expression of COMMD7 protein. The IC50 value of DDP is determined by MTT assay. The cell proliferation ability was measured by colony formation test. The apoptosis ability was measured by flow cytometry. The interaction between Linc00852, miR-514a-5p, and COMMD7 was confirmed by luciferase reporter gene assay and RNA pull-down assay. Xenograft tumor model was used to study the effect of Linc00852 on DDP resistance in vivo. RESULTS: Linc00852 was up-regulated in DDP-resistant GC cells and their secreted exosomes. Down-regulating Linc00852 facilitated the sensitivity of DDP-resistant GC cells to DDP. Linc00852 bound to miR-514a-5p and COMMD7 was a target of miR-514a-5p. Linc00852 could regulate COMMD7 expression via targeting miR-514a-5p. Exosomes from DDP-resistant GC cells enhanced the resistance of recipient GC cells to DDP via exosomal delivery of Linc00852. Depletion of Linc00852 repressed the growth and DDP resistance of GC cells in vivo. CONCLUSION: Linc00852 from DDP-resistant tumor cell-derived Exos regulates COMMD7 to promote drug resistance of GC cells through miR-514a-5p.