Objective: To investigate the expression and significance of MNAT1 in non-small cell lung cancer (NSCLC) and to explore the biological impact of MNAT1 expression in lung cancer cells at the cellular level and related signaling pathway. Methods: Forty-eight cases of NSCLC tissues and paired normal tissues was collected at Nanfang Hospital, Southern Medical University from 2015 to 2017. The expression level of MNAT1 was detected by immunohistochemistry, and the relationship between MNAT1 and clinicopathological features was analyzed. The expression of MNAT1 was detected in lung cancer cells, MNAT1 level was analyzed after knocking down in A549 and H322 cells by siRNA; Plasmid vector of overexpressing MNAT1 was constructed, followed by transfecting H1299 cells and observing proliferation and migration at the cellular level. Flow cytometry was used to analyze the effect of the expression of MNAT1 on cell cycle, and Western blot was used to explore the possible molecular mechanism of MNAT1 on cell proliferation and cell cycle. Results: Immunohistochemistry showed that the expression score of MNAT1 was (4.07±3.55) in normal lung tissue and (7.33±4.09) in NSCLC tissue (P<0.01), and correlated with lymph node metastasis. At the cellular level, MNAT1 promoted cell proliferation(P<0.05), migration(P<0.05) and cell cycle progression(P<0.01). Conclusions: MNAT1 may be involved in the development of non-small cell lung cancer.MNAT1 affects cell cycle and proliferation through the Akt/p21 pathway.
目的： 探讨MNAT1在非小细胞肺癌组织中的表达及意义；观察MNAT1在细胞水平上对肺癌细胞的生物学行为的影响并探讨其可能潜在的通路。 方法： （1）收集南方医科大学南方医院2015至2017年48例非小细胞肺癌组织及配对正常组织标本，用免疫组织化学法检测MNAT1的表达水平，分析其与非小细胞肺癌临床病理学特征之间的关系。（2）检测肺癌细胞株中MNAT1的表达水平，利用siRNA沉默A549及H322细胞株的MNAT1，同时构建过表达MNAT1质粒载体并转染H1299细胞，观察MNAT1的表达在细胞水平上对非小细胞肺癌细胞增殖、迁移的影响。（3）采用流式细胞术分析MNAT1低表达及过表达对细胞周期的影响，并用Western blot实验探索MNAT1对细胞增殖和细胞周期影响的可能分子机制。 结果： 免疫组织化学结果显示，MNAT1在正常肺组织的表达分数为（4.07±3.55），非小细胞肺癌组织的表达分数为（7.33±4.09；P<0.01），且与淋巴结转移相关；在细胞中，MNAT1促进了细胞的增殖（P<0.05）、迁移（P<0.05）及细胞周期（P<0.01）的进程。 结论： MNAT1可能参与了非小细胞肺癌的发生发展过程。MNAT1可能通过Akt/p21途径影响细胞周期和增殖。.
Keywords: Cell cycle; Cell proliferation; Cyclin-dependent kinases; Gene silencing; Lung neoplasms.