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第43卷第8期 南京医科大学学报(自然科学版)
2023年8月 Journal of Nanjing Medical University(Natural Sciences) ·1061 ·
·基础研究·
棕榈酰化转移酶9调控非小细胞肺癌增殖、迁移、侵袭及相关机
制研究
周 容,高琛梓,赵廷枫,顾 遥,王 倩 *
南京医科大学罕见代谢性疾病研究重点实验室,生物化学与分子生物学系,江苏省人类功能基因组重点实验室,江苏 南京
211166
[摘 要] 目的:探讨棕榈酰化转移酶 9(zinc finger DHHC⁃type containing 9,ZDHHC9)在非小细胞肺癌(non⁃small cell lung
cancer,NSCLC)中的表达及预后,及ZDHHC9对NSCLC细胞增殖、迁移和侵袭能力的影响及作用机制。方法:通过NCBI GEC
数据库和基于基因表达水平值的交互式分析平台(gene expression profiling interactive analysis,GEPIA)数据库分析ZDHHC9在
NSCLC 中的表达及其与患者预后之间的关系。利用实时定量 PCR(Real⁃time qPCR)检测正常支气管上皮细胞系(16HBE)及
NSCLC细胞系(A549、H1299、H1703)的表达情况。在H1703和A549细胞系中敲降ZDHHC9,利用CCK⁃8实验检测细胞增殖能
力,Transwell和划痕实验检测细胞迁移、侵袭能力,Western blot检测相关蛋白水平变化。结果:GEO和GEPIA数据库生物信息
技术分析结果显示,ZDHHC9 在 NSCLC 组织中较癌旁组织显著升高,并且 ZDHHC9 表达量与患者的无病生存率相关(P <
0.01)。敲降 ZDHHC9 后,H1703 和 A549 细胞增殖活力显著下降,同时侵袭和迁移能力受到抑制,并且敲降 ZDHHC9 降低
NSCLC细胞脂肪酸合成关键酶的表达水平。结论:ZDHHC9可能通过调控NSCLC细胞脂肪酸合成促进NSCLC细胞的增殖、迁
移和侵袭。
[关键词] 棕榈酰化转移酶9;非小细胞肺癌;增殖;迁移;侵袭;脂代谢
[中图分类号] R734.2 [文献标志码] A [文章编号] 1007⁃4368(2023)08⁃1061⁃07
doi:10.7655/NYDXBNS20230804
ZDHHC9 regulates the proliferation,migration and invasion of non⁃small cell lung cancer
ZHOU Rong,GAO Chenzi,ZHAO Tingfeng,GU Yao,WANG Qian *
Key Laboratory of Rare Metabolic Disease,Department of Molecular Biology and Biochemistry,Nanjing Medical
University,the Key Laboratory of Human Functional Genomics of Jiangsu Province,Nanjing 211166,China
[Abstract] Objective:To investigate the expression and prognosis of zinc finger DHHC⁃type containing 9(ZDHHC9)in non⁃small
cell lung cancer(NSCLC)and explore its effect and mechanism on the proliferation,migration and invasion of NSCLC cells. Methods:
The expressions of ZDHHC9 in NSCLC and its relationship with prognosis were analyzed by NCBI GEO datasets and Gene Expression
Profiling Interactive Analysis(GEPIA)database. The expression levels of ZDHHC9 in normal bronchial epithelial cell line(16HBE)
and NSCLC cell lines(A549,H1299,H1703)were detected by real⁃time qPCR. ZDHHC9 was knocked down by siRNA in H1703 and
A549 cell lines. Cell proliferation was detected by CCK⁃8 assay. Cell migration and invasion were detected by transwell and scratch
assay,and the indicated protein levels were detected by Western blot. Results:The results of GEO datasets and GEPIA data analysis
showed that ZDHHC9 was significantly increased in NSCLC tissues compared with para⁃cancer tissues,and the expression level of
ZDHHC9 correlated with disease⁃free survival of patients by GEPIA data analysis(P < 0.01). The proliferation activity of H1703 and
A549 cells was significantly decreased following ZDHHC9 knockdown. Compared with control,inhibition of ZDHHC9 in both H1703
and A549 cells displayed significant decreases in the migratory and invasive abilities assessed by the wound healing and transwell
assays. Of note,ZDHHC9 knocking down decreased the protein levels of key fatty acid synthesis enzymes in NSCLC cells. Conclusion:
ZDHHC9 may promote proliferation,migration and invasion of NSCLC cells by regulating fatty acid synthesis.
[Key words] ZDHHC9;non⁃small cell lung cancer;proliferation;migration;invasion;fatty acid metabolism
[基金项目] 国家自然科学基金(82170838) [J Nanjing Med Univ,2023,43(08):1061⁃1067]
∗
通信作者(Corresponding author),E⁃mail:wqian@njmu.edu.cn