Abstract：
OBJECTIVE: This study aimed to conclude the effect and mechanism of ZIC2 on immune infiltration in lung adenocarcinoma (LUAD).
METHODS: Expression of ZIC2 in several kinds of normal tissues of TCGA data was analyzed and its correlation with the baseline characteristic of LUAD patients were analyzed. The immune infiltration analysis of LUAD patients was performed by CIBERSORT algorithm. The correlation analysis between ZIC2 and immune cell composition was performed. Additionally, the potential upstream regulatory mechanisms of ZIC2 were predicted to identify the possible miRNAs and lncRNAs that regulated ZIC2 in LUAD. In vitro and in vivo experiments were also conducted to confirm the potential effect of ZIC2 on cell proliferation and invasion ability of LUAD cells.
RESULTS: ZIC2 expression was decreased in various normal tissues, but increased in multiple tumors, including LUAD, and correlated with the prognosis of LUAD patients. Enrichment by GO and KEGG suggested the possible association of ZIC2 with cell cycle and p53 signal pathway. ZIC2 expression was significantly correlated with T cells CD4 memory resting, Macrophages M1, and plasma cells, indicating that dysregulated ZIC2 expression in LUAD may directly influence immune infiltration. ZIC2 might be regulated by several different lncRNA-mediated ceRNA mechanisms. In vitro experiments validated the promotive effect of ZIC2 on cell viability and invasion ability of LUAD cells. In vivo experiments validated ZIC2 can accelerate tumor growth in nude mouse.
CONCLUSIONS: ZIC2 regulated by different lncRNA-mediated ceRNA mechanisms may play a critical regulatory role in LUAD through mediating the composition of immune cells in tumor microenvironment.
METHODS: Expression of ZIC2 in several kinds of normal tissues of TCGA data was analyzed and its correlation with the baseline characteristic of LUAD patients were analyzed. The immune infiltration analysis of LUAD patients was performed by CIBERSORT algorithm. The correlation analysis between ZIC2 and immune cell composition was performed. Additionally, the potential upstream regulatory mechanisms of ZIC2 were predicted to identify the possible miRNAs and lncRNAs that regulated ZIC2 in LUAD. In vitro and in vivo experiments were also conducted to confirm the potential effect of ZIC2 on cell proliferation and invasion ability of LUAD cells.
RESULTS: ZIC2 expression was decreased in various normal tissues, but increased in multiple tumors, including LUAD, and correlated with the prognosis of LUAD patients. Enrichment by GO and KEGG suggested the possible association of ZIC2 with cell cycle and p53 signal pathway. ZIC2 expression was significantly correlated with T cells CD4 memory resting, Macrophages M1, and plasma cells, indicating that dysregulated ZIC2 expression in LUAD may directly influence immune infiltration. ZIC2 might be regulated by several different lncRNA-mediated ceRNA mechanisms. In vitro experiments validated the promotive effect of ZIC2 on cell viability and invasion ability of LUAD cells. In vivo experiments validated ZIC2 can accelerate tumor growth in nude mouse.
CONCLUSIONS: ZIC2 regulated by different lncRNA-mediated ceRNA mechanisms may play a critical regulatory role in LUAD through mediating the composition of immune cells in tumor microenvironment.
摘要：
目的：本研究旨在探讨ZIC2在肺腺癌(LUAD)免疫浸润中的作用及其机制。
方法：分析TCGA数据中几种正常组织中ZIC2的表达，并分析其与LUAD患者基线特征的相关性。LUAD患者的免疫浸润分析采用CIBERSORT算法。对ZIC2与免疫细胞组成进行相关性分析。此外,预测ZIC2的潜在上游调控机制,以鉴定在LUAD中可能调控ZIC2的miRNA和lncRNA.还进行了体外和体内实验以证实ZIC2对LUAD细胞的细胞增殖和侵袭能力的潜在影响。
结果：ZIC2在各种正常组织中表达降低，但在多个肿瘤中增加，包括LUAD,并与LUAD患者的预后相关。GO和KEGG的富集表明ZIC2可能与细胞周期和p53信号通路有关。ZIC2表达与T细胞CD4记忆静息、巨噬细胞M1和浆细胞,表明LUAD中ZIC2表达失调可能直接影响免疫浸润。ZIC2可能受几种不同的lncRNA介导的ceRNA机制调控。体外实验验证了ZIC2对LUAD细胞活力和侵袭能力的促进作用。体内实验验证了ZIC2可以加速裸鼠中的肿瘤生长。
结论：由不同lncRNA介导的ceRNA机制调控的ZIC2可能通过介导肿瘤微环境中免疫细胞的组成在LUAD中发挥关键的调节作用。
方法：分析TCGA数据中几种正常组织中ZIC2的表达，并分析其与LUAD患者基线特征的相关性。LUAD患者的免疫浸润分析采用CIBERSORT算法。对ZIC2与免疫细胞组成进行相关性分析。此外,预测ZIC2的潜在上游调控机制,以鉴定在LUAD中可能调控ZIC2的miRNA和lncRNA.还进行了体外和体内实验以证实ZIC2对LUAD细胞的细胞增殖和侵袭能力的潜在影响。
结果：ZIC2在各种正常组织中表达降低，但在多个肿瘤中增加，包括LUAD,并与LUAD患者的预后相关。GO和KEGG的富集表明ZIC2可能与细胞周期和p53信号通路有关。ZIC2表达与T细胞CD4记忆静息、巨噬细胞M1和浆细胞,表明LUAD中ZIC2表达失调可能直接影响免疫浸润。ZIC2可能受几种不同的lncRNA介导的ceRNA机制调控。体外实验验证了ZIC2对LUAD细胞活力和侵袭能力的促进作用。体内实验验证了ZIC2可以加速裸鼠中的肿瘤生长。
结论：由不同lncRNA介导的ceRNA机制调控的ZIC2可能通过介导肿瘤微环境中免疫细胞的组成在LUAD中发挥关键的调节作用。
