Tong Ruiying, Meng Jiqing, Wu Ting, Wu Zhouying, Yin Yunhao, Yu Lan
Clinical Medical Research Center, Inner Mongolian People's Hospital, Hohhot 010017, China.
Department of Pharmacy, Inner Mongolian People's Hospital, Hohhot 010017, China.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2024 Oct;40(10):894-900.
Objective To investigate the impact of dipeptidyl peptidase 3 (DPP3) on the immune escape of gastric cancer cells by regulating the expression of major histocompatibility complex class I chain-related gene B (MICB). Methods Knocking down DPP3 in MKN-45 human gastric cancer cells and overexpressing DPP3 in MGC-803 human gastric cancer cells, observing changes in cell proliferation, migration ability, and responses to natural killer (NK) cell cytotoxicity; using whole-transcriptome sequencing to identify the MICB gene, and knocking down MICB in DPP3-overexpressing cells to verify changes in cellular behavior. In C57 mice, the in vivo tumorigenic ability of DPP3-knockout cells and the infiltration of CD56 cells in tissues were examined. Results Knocking out DPP3 promoted the proliferation and migration of gastric cancer cells, reduced MICB expression, and made the cells less sensitive to NK cell cytotoxicity; the tumorigenic ability in mice increased and CD56 cells tissue infiltration decreased by DPP3 knocking out in the gastric cancer cells, but DPP3 overexpression showed the opposite results. Knocking down MICB could reverse the phenotypic changes induced by high DPP3 expression. Conclusion DPP3 inhibits the immune escape of gastric cancer cells by downregulating MICB expression.
目的 通过调节主要组织相容性复合体I类链相关基因B（MICB）的表达，探讨二肽基肽酶3（DPP3）对胃癌细胞免疫逃逸的影响。方法 在人胃癌MKN-45细胞中敲低DPP3，在人胃癌MGC-803细胞中过表达DPP3，观察细胞增殖、迁移能力及对自然杀伤（NK）细胞细胞毒性反应的变化；采用全转录组测序鉴定MICB基因，并在过表达DPP3的细胞中敲低MICB以验证细胞行为的变化。在C57小鼠中，检测DPP3基因敲除细胞的体内致瘤能力及组织中CD56细胞的浸润情况。结果 敲除DPP3促进胃癌细胞增殖和迁移，降低MICB表达，使细胞对NK细胞细胞毒性的敏感性降低；敲除胃癌细胞中的DPP3可使小鼠体内致瘤能力增强，CD56细胞组织浸润减少，但过表达DPP3则呈现相反结果。敲低MICB可逆转高表达DPP3诱导的表型变化。结论 DPP3通过下调MICB表达抑制胃癌细胞的免疫逃逸。
