School of Life Sciences, Anhui University, Hefei, Anhui, China.
Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, China.
J Gene Med. 2024 Jan;26(1):e3664. doi: 10.1002/jgm.3664.
The primary reason for tumor-related deaths worldwide is lung adenocarcinoma (LUAD). The oncogene IQ motif-containing GTPase activating protein 3 (IQGAP3) is crucial for contributing to tumor initiation and progression. However, the precise function and molecular mechanism of IQGAP3 in LUAD remain unknown. The present study aimed to investigate the expression, prognosis, mechanism and tumor immunity associated with IQGAP3 in LUAD.
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.
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.
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.
全球肿瘤相关死亡的主要原因是肺腺癌 (LUAD)。癌基因 IQ -motif 富含 GTP 酶激活蛋白 3 (IQGAP3) 对于促进肿瘤的发生和发展至关重要。然而,IQGAP3 在 LUAD 中的精确功能和分子机制尚不清楚。本研究旨在探讨 IQGAP3 在 LUAD 中的表达、预后、机制和肿瘤免疫相关。
利用癌症基因组图谱 (TCGA) 数据库分析 IQGAP3 与 LUAD 不良预后的关系。在肺癌组织和细胞系中进一步验证了这一点。通过在 LUAD 细胞系中沉默 IQGAP3 来研究 IQGAP3 的功能。利用 starBase 数据库预测与 IQGAP3 相关的 microRNA (miRNA) 和长链非编码 RNA,并通过增强 miRNA 的功能验证预测。最后,通过 Spearman 相关分析评估 IQGAP3 与肿瘤免疫的关系。
TCGA 数据库显示,IQGAP3 水平较高与 LUAD 患者的晚期肿瘤分期、N 分期和不良预后相关。为了证实这一点,我们在肺癌组织和细胞系中进行了实验,发现沉默 IQGAP3 可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,与 GSEC、AC005034.3 和 TYMSOS 呈正相关。此外,将 miRNA-mimics 引入肺癌细胞中可显著抑制癌细胞的生长和迁移。之后,IQGAP3 的水平与肿瘤中免疫细胞的浸润呈正相关。
这些结果表明,IQGAP3 显著促进 LUAD 进展,可作为 LUAD 的预后生物标志物。此外,IQGAP3 很可能在 LUAD 中受 GSEC/TYMSOS-hsa-miR-101-3p 轴和 AC005034.3-hsa-miR-135a-5p 轴的调节。