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
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南京医科大学罕见代谢性疾病研究重点实验室

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国家自然科学基金面上项目


ZDHHC9 regulates the proliferation, migration and invasion of non-small cell lung cancer and related mechanisms
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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

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General program of National Natural Science Foundation of China

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    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 datasets数据库和GEPIA(Gene Expression Profiling Interactive Analysis)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ZDHHC9在56例NSCLC患者的癌和癌旁组织以及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:ZDHHC9在NSCLC组织中较癌旁组织显著升高,GEO datasets和GEPIA数据库生物信息技术分析结果与临床结果相吻合,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。

    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 datasets and Gene Expression Profiling Interactive Analysis (GEPIA) database. The expression levels of ZDHHC9 in tumor and adjacent tissues of 56 NSCLC patients, 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 mi-gration and invasion were detected by Transwell and Scratch assay, and the indicated protein levels were detected by Western blot. Results: ZDHHC9 was significantly higher in NSCLC tissue than in paracancer tissue. Moreover, the expression of ZDHHC9 was upregulated in the lung cancer microarray from GEO datasets, 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 mi-gratory and invasive abilities assessed by the wound healing and transwell assays. Of note, knock-ing ZDHHC9 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 in NSCLC cells.

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  • 收稿日期:2023-03-24
  • 最后修改日期:2023-04-13
  • 录用日期:2023-08-09
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