微小RNA-152/人类白细胞抗原-G轴影响非小细胞肺癌细胞的增殖和免疫逃逸。
The microRNA-152/human leukocyte antigen-G axis affects proliferation and immune escape of non-small cell lung cancer cells.
作者信息
Fu Jun, Mao Jun, Wang Chun
机构信息
Department of Thoracic Surgery, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Department of Thyroid and Breast Surgery, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
出版信息
J Int Med Res. 2020 Nov;48(11):300060520970758. doi: 10.1177/0300060520970758.
OBJECTIVE
To investigate the role of human leukocyte antigen (HLA-G) on proliferation, invasion, and immune escape in non-small cell lung cancer (NSCLC).
METHODS
The relationship between HLA-G and overall survival (OS) of NSCLC patients was analyzed using the KMPlot database. The expression of micro (mi)R-152 or HLA-G was modulated by transfecting synthetic oligonucleotides, and the impact of the miR-152/HLA-G axis on proliferation, invasion, colony formation in soft agar, and tolerance to natural killer (NK) cell cytolysis was measured.
RESULTS
Bioinformatics analysis showed that high HLA-G expression was correlated with poor OS in NSCLC patients. The tolerance of NSCLC cells to NK cytotoxicity was negatively correlated with HLA-G and positively correlated with miR-152 expression. Over-expressing miR-152 inhibited HLA-G expression in A549 cells and attenuated cell proliferation, migration, colony formation ability, and tolerance to NK cells. However, blocking HLA-G expression by small interfering RNA did not affect migration or colony formation, but only proliferation and tolerance to NK cells and . Blocking Ig-like transcript 2 on the surface of NK cells increased their killing effect in the presence of high HLA-G expression.
CONCLUSIONS
miR-152/HLA-G axis plays an oncogenic role in NSCLC by affecting cell proliferation and immune escape.
目的
探讨人类白细胞抗原（HLA - G）在非小细胞肺癌（NSCLC）增殖、侵袭及免疫逃逸中的作用。
方法
使用KMPlot数据库分析HLA - G与NSCLC患者总生存期（OS）的关系。通过转染合成寡核苷酸来调节微小（mi）R - 152或HLA - G的表达，并检测miR - 152/HLA - G轴对增殖、侵袭、软琼脂集落形成以及对自然杀伤（NK）细胞溶解的耐受性的影响。
结果
生物信息学分析表明，NSCLC患者中高HLA - G表达与较差的OS相关。NSCLC细胞对NK细胞毒性的耐受性与HLA - G呈负相关，与miR - 152表达呈正相关。过表达miR - 152可抑制A549细胞中HLA - G的表达，并减弱细胞增殖、迁移、集落形成能力以及对NK细胞的耐受性。然而，用小干扰RNA阻断HLA - G表达并不影响迁移或集落形成，仅影响增殖以及对NK细胞的耐受性。在高HLA - G表达情况下，阻断NK细胞表面的免疫球蛋白样转录物2可增强其杀伤作用。
结论
miR - 152/HLA - G轴通过影响细胞增殖和免疫逃逸在NSCLC中发挥致癌作用。
Zotero 插件