Haohao Li1, Chunlin Zhao1, Hongchao Zhao1, Guanghui Liu1, Haoxun Mao1, Yanfen Liu2. 1. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. 2. Department of Oncology, Biological Therapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address: Liuyanfen2332@163.com.
Abstract
OBJECTIVE: Gastric cancer (GC) is a malignant tumor originated from gastric mucosa. Without effective therapy, this study was to investigate the mechanism of long intergenic noncoding RNA 00936 (linc00936)/microRNA-425-3p (miR-425-3p)/monocyte chemotactic protein-induced protein 1 (ZC3H12A) axis mediating immune escape of GC cells. METHODS: Peripheral blood samples, GC tissues and adjacent tissues were collected. The levels of CD3+, CD4+, and CD8+ in peripheral blood were detected. The expression levels of linc00936, miR-425-3p and ZC3H12A in GC tissues and cells were detected. The correlation between the expression of linc00936 in the tissues and the levels of CD3+, CD4+ and CD8+ in the peripheral blood of GC patients was analyzed. Cytokine-induced killer (CIK) cells were induced, and co-incubated with GC cells. BGC-823 and MKN-45 cells were screened and transfected with linc00936- or miR-425-3p-related oligonucleotides to figure out their roles in immune escape, migration, apoptosis and the cytotoxicity of CIK cells in GC cells. RESULTS: Elevated miR-425-3p and reduced linc00936, and ZC3H12A expression levels were found in GC tissues and cells. Linc00936 expression was positively correlated with CD3+ and CD4+, and negatively correlated with CD8+ in peripheral blood of patients with GC. Up-regulating linc00936 or down-regulating miR-425-3p inhibited immune escape, migration, promoted apoptosis of GC cells, as well induced CIK cell cytotoxicity to GC cells. Down-regulated linc00936 or elevated miR-425-3p facilitated immune escape, migration, depressed apoptosis of GC cells, and reduced the cytotoxicity of CIK cells to GC cells. CONCLUSION: The study concludes that up-regulated linc00936 or silenced miR-425-3p inhibits immune escape of GC cells via elevation of ZC3H12A.
OBJECTIVE:Gastric cancer (GC) is a malignant tumor originated from gastric mucosa. Without effective therapy, this study was to investigate the mechanism of long intergenic noncoding RNA 00936 (linc00936)/microRNA-425-3p (miR-425-3p)/monocyte chemotactic protein-induced protein 1 (ZC3H12A) axis mediating immune escape of GC cells. METHODS: Peripheral blood samples, GC tissues and adjacent tissues were collected. The levels of CD3+, CD4+, and CD8+ in peripheral blood were detected. The expression levels of linc00936, miR-425-3p and ZC3H12A in GC tissues and cells were detected. The correlation between the expression of linc00936 in the tissues and the levels of CD3+, CD4+ and CD8+ in the peripheral blood of GC patients was analyzed. Cytokine-induced killer (CIK) cells were induced, and co-incubated with GC cells. BGC-823 and MKN-45 cells were screened and transfected with linc00936- or miR-425-3p-related oligonucleotides to figure out their roles in immune escape, migration, apoptosis and the cytotoxicity of CIK cells in GC cells. RESULTS: Elevated miR-425-3p and reduced linc00936, and ZC3H12A expression levels were found in GC tissues and cells. Linc00936 expression was positively correlated with CD3+ and CD4+, and negatively correlated with CD8+ in peripheral blood of patients with GC. Up-regulating linc00936 or down-regulating miR-425-3p inhibited immune escape, migration, promoted apoptosis of GC cells, as well induced CIK cell cytotoxicity to GC cells. Down-regulated linc00936 or elevated miR-425-3p facilitated immune escape, migration, depressed apoptosis of GC cells, and reduced the cytotoxicity of CIK cells to GC cells. CONCLUSION: The study concludes that up-regulated linc00936 or silenced miR-425-3p inhibits immune escape of GC cells via elevation of ZC3H12A.
Authors: Angelina Huseinovic; Annelieke Jaspers; Annina P van Splunter; Hanne Sørgård; Saskia M Wilting; Dorian R A Swarts; Ida H van der Meulen; Victor W van Beusechem; Renée X de Menezes; Renske D M Steenbergen Journal: Int J Mol Sci Date: 2022-04-26 Impact factor: 6.208