Identification and validation of non‐coding RNA‐mediated high expression of IQGAP3 in poor prognosis of lung adenocarcinoma

小RNA 基因沉默 腺癌 癌基因 肺癌 生物 癌症研究 癌症 肿瘤科 内科学 基因 医学 细胞周期 遗传学
作者
Ziwei Su,Yang Wang,Jialing Cao,Jie Ma,Guangzhao Wang,Huijuan Ren,Yihan Zhang,Kangliang Sheng,Xueying Zhu,Yongzhong Wang
出处
期刊:Journal of Gene Medicine [Wiley]
卷期号:26 (1) 被引量:1
标识
DOI:10.1002/jgm.3664
摘要

Abstract Background 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. 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.

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