Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Department of Oncology, Biological Therapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Int Immunopharmacol. 2021 Jun;95:107559. doi: 10.1016/j.intimp.2021.107559. Epub 2021 Mar 20.
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.
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.
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.
The study concludes that up-regulated linc00936 or silenced miR-425-3p inhibits immune escape of GC cells via elevation of ZC3H12A.
胃癌（GC）是一种起源于胃黏膜的恶性肿瘤。本研究旨在探讨长链非编码 RNA 00936（linc00936）/微小 RNA-425-3p（miR-425-3p）/单核细胞趋化蛋白诱导蛋白 1（ZC3H12A）轴介导 GC 细胞免疫逃逸的机制。
收集外周血样本、GC 组织和相邻组织。检测外周血中 CD3、CD4 和 CD8 的水平。检测 GC 组织和细胞中 linc00936、miR-425-3p 和 ZC3H12A 的表达水平。分析 GC 患者组织中 linc00936 的表达与外周血中 CD3、CD4 和 CD8 水平的相关性。诱导细胞因子诱导的杀伤（CIK）细胞，并与 GC 细胞共孵育。筛选 BGC-823 和 MKN-45 细胞，并转染 linc00936 或 miR-425-3p 相关寡核苷酸，以研究其在 GC 细胞免疫逃逸、迁移、凋亡和 CIK 细胞细胞毒性中的作用。
GC 组织和细胞中发现 miR-425-3p 升高和 linc00936、ZC3H12A 表达水平降低。GC 患者外周血中 linc00936 表达与 CD3 和 CD4 呈正相关，与 CD8 呈负相关。上调 linc00936 或下调 miR-425-3p 抑制 GC 细胞免疫逃逸、迁移，促进凋亡，并诱导 CIK 细胞对 GC 细胞的细胞毒性。下调 linc00936 或上调 miR-425-3p 促进 GC 细胞免疫逃逸、迁移，抑制凋亡，并降低 CIK 细胞对 GC 细胞的细胞毒性。
研究表明，上调 linc00936 或沉默 miR-425-3p 通过上调 ZC3H12A 抑制 GC 细胞的免疫逃逸。
