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

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 LU...

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Veröffentlicht in:The journal of gene medicine 2024-01, Vol.26 (1), p.e3664-n/a
Hauptverfasser: Su, Ziwei, Wang, Yang, Cao, Jialing, Ma, Jie, Wang, Guangzhao, Ren, Huijuan, Zhang, Yihan, Sheng, Kangliang, Zhu, Xueying, Wang, Yongzhong
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Sprache:eng
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Zusammenfassung: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. The diagnostic and prognostic values of IQ motif‐containing GTPase activating protein 3 (IQGAP3) overexpression in lung adenocarcinoma (LUAD) patients are revealed in the present study. An upstream regulatory mechanism of IQGAP3 in LUAD, namely, the TYMSOS/GSEC‐hsa‐miR‐101‐3p axis and the AC005034.3‐hsa‐miR‐135a‐5p axis, was also investigated.
ISSN:1099-498X
1521-2254
DOI:10.1002/jgm.3664