METHODS: The relationship between IQGAP3 and the poor prognosis of LUAD was analyzed using The Cancer Genome Atlas (TCGA) database. This analysis was further validated on lung cancer tissues and cell lines. The function of IQGAP3 was investigated by silencing it in LUAD cell lines. To predict microRNA (miRNA) and long non-coding RNA associated with IQGAP3, the starBase database was utilized, and the predictions were verified by enhancing the function of miRNA. Finally, the relationship between IQGAP3 and tumor immunity was evaluated using Spearman\'s correlation analysis.
RESULTS: TCGA database revealed that higher levels of IQGAP3 were associated with advanced tumor stage, N stage and poor prognosis in LUAD patients. To confirm that, we conducted experiments on lung cancer tissues and cell lines and found that silencing IQGAP3 significantly inhibited tumor cell proliferation and migration. The expression of IQGAP3 showed a negative correlation with has-miR-101-3p and has-miR-135a-5p, whereas it showed a positive correlation with GSEC, AC005034.3 and TYMSOS. Furthermore, the introduction of miRNA-mimics into lung cancer cell resulted in a significant inhibition of cancer cell growth and migration. Following that, the level of IQGAP3 showed a positive correlation with the infiltration of immune cells in tumors.
CONCLUSIONS: These results reveal that IQGAP3 significantly promotes LUAD progression and could serve as a prognostic biomarker for LUAD. Furthermore, IQGAP3 is most likely regulated by the GSEC/TYMSOS-hsa-miR-101-3p axis and the AC005034.3-hsa-miR-135a-5p axis in LUAD.
方法:使用癌症基因组图谱(TCGA)数据库分析IQGAP3与LUAD不良预后之间的关系。该分析在肺癌组织和细胞系上进一步验证。通过在LUAD细胞系中沉默IQGAP3来研究IQGAP3的功能。为了预测与IQGAP3相关的microRNA(miRNA)和长链非编码RNA,利用了starBase数据库,并通过增强miRNA的功能来验证预测结果。最后,采用Spearman相关分析评价IQGAP3与肿瘤免疫的关系。
结果:TCGA数据库显示,较高水平的IQGAP3与晚期肿瘤分期相关,LUAD患者的N分期与预后不良。为了证实这一点,我们对肺癌组织和细胞系进行了实验,发现沉默IQGAP3显著抑制肿瘤细胞的增殖和迁移。IQGAP3的表达与has-miR-101-3p和has-miR-135a-5p呈负相关,而它与GSEC呈正相关,AC005034.3和TYMSOS。此外,将miRNA模拟物引入肺癌细胞导致癌细胞生长和迁移的显著抑制.在此之后,IQGAP3水平与肿瘤免疫细胞浸润呈正相关。
结论:这些结果表明IQGAP3显著促进LUAD进展,并可作为LUAD的预后生物标志物。此外,IQGAP3很可能受LUAD中的GSEC/TYM0S-hsa-miR-101-3p轴和AC005034.3-hsa-miR-135a-5p轴调节。