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南京医科大学学报(自然科学版)                                  第41卷第7期
               ·956 ·                     Journal of Nanjing Medical University(Natural Sciences)   2021年7月


             ·基础医学·

              miR⁃16/15a 小鼠NK细胞功能及其对结肠癌移植瘤敏感度分析
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              魏莹莹,胡翔宇,祖丽皮耶·艾尔肯,龚卫娟,贾筱琴                     *
              扬州大学医学院基础医学系,江苏 扬州               225001




             [摘    要] 目的:观察miR⁃16是否通过调节NKG2D表达而影响自然杀伤(natural killer,NK)细胞的生物学功能及其抗肿瘤活
              性。方法:miR⁃16/15a 小鼠和对照小鼠经皮下注射MC38细胞制备结肠癌移植瘤模型,观察两组小鼠皮下实体瘤生长情况;
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              比较普通小鼠生理或荷瘤状态下NK1.1 NKG2D 细胞和NK1.1 NKG2D 细胞内miR⁃16的表达;分析生理及荷瘤状态下miR⁃16/
              15a 小鼠NK细胞NKG2D表达、γ干扰素(interferon⁃γ,IFN⁃γ)分泌及细胞毒性作用。结果:与同品系小鼠比较,miR⁃16/15a 小
                                                                                                           -/-
                 -/-
              鼠中MC38结肠癌移植瘤的生长受到显著抑制,生理状态小鼠NK1.1 NKG2D 细胞miR⁃16的表达明显低于NK1.1 NKG2D 细胞,
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              而在荷瘤小鼠来源的两组细胞中无明显差异;与野生型小鼠相比,生理及荷瘤状态下的miR⁃16/15a 小鼠NK1.1 NKG2D 细胞的
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              比例及NK细胞活性无明显变化。结论:miR⁃16/15a敲除抑制MC38结肠癌移植瘤生长,而miR⁃16/15a敲除小鼠体内NK细胞的比
              例及功能及荷瘤状态下NK细胞活性并无明显变化,提示miR⁃16/15a缺失并非通过NK细胞抑制MC38结肠癌移植瘤生长。
             [关键词] miR⁃16/miR⁃15a;结肠癌;NK细胞;NKG2D;活性
             [中图分类号] R735.3                   [文献标志码] A                        [文章编号] 1007⁃4368(2021)07⁃956⁃07
              doi:10.7655/NYDXBNS20210704
              Analysis of NK cell function in miR⁃16/15a    -/-  mice and its sensitivity to colon transplanted
              tumor
                                                                                  *
              WEI Yingying,HU Xiangyu,ZULIEPIERRE Elken,GONG Weijuan,JIA Xiaoqin
              Department of Basic Medicine,Medical Academy,Yangzhou Univeristy,Yangzhou 225001,China

             [Abstract] Objective:To investigate whether miR⁃16 affected the biological function and anti⁃tumor activity of natural killer(NK)
                                                                           -/-
              cells by regulating NKG2D expression. Methods:The control mice and miR⁃16/15a  mice were subcutaneously injected with MC38
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              cells to prepare the colon cancer tumor model,and the growth of transplanted colon cancer in miR⁃16/15a mice and control mice were
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              observed. Then,the transcription level of miR⁃16 in NK1.1 NKG2D cells and NK1.1 NKG2D cells was compared under physiological
              or tumor⁃bearing conditions in wild⁃type mice. Finally,in comparison with wild⁃type mice,we analyzed NKG2D expression,interferon⁃γ
                                                            -/-
             (IFN⁃γ)production and cytotoxicity of NK cells in miR⁃16/15a mice. Results:Compared with the control mice,the growth of MC38
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              transplanted tumor was significantly inhibited in miR⁃16/15a -/-  mice. The transcription level of miR⁃16 in NK1.1 NKG2D cells was
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                                                ⁃
              significantly lower than that in NK1.1 NKG2D cells in normal mice,while there was no significant difference between the two groups
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              in tumor ⁃ bearing mice. Compared with the control mice,NK1.1 NKG2D cell frequency and NK cell activity did not change
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              significantly in miR⁃16/15a mice. Conclusion:MiR⁃16/15a knockout inhibited the growth of MC38 transplanted tumor,while the
              ratio and function of NK cells in miR⁃16/15a knockout mice and the activity of NK cells in the tumor⁃bearing state did not significantly
              change,suggesting that miR⁃16/15a dificiency does not inhibit the growth of MC38 transplanted tumor though NK cells.
             [Key words] miR⁃16/miR⁃15a;colon cancer;natural killer cell;NKG2D;activity
                                                                            [J Nanjing Med Univ,2021,41(07):956⁃962]
                                                                     microRNA(miRNA)是一类内生的、长度约为
                                                                20~24个核苷酸的非编码RNA,不仅参与细胞增殖、
             [基 金 项 目] 国 家 自 然 科 学 基 金(81873867,81273214,
              81671547)                                         发育、分化、凋亡等基本生理过程,还和肿瘤、炎症
                                                                                        [1]
              ∗                                                 等病理过程有着密切关系 。miR⁃16和miR⁃15a基
              通信作者(Corresponding author),E⁃mail: jxqbl@163.com
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