Expression and biological role of potassium voltage-gated channel subfamily G member 1 in lung cancer
CHENG Feng1, PENG Shiqing1, CAO Yang1, LU Yimin2
（1. School of Medicine, Jiangsu University, Zhenjiang Jiangsu 212013; 2. Pulmonary and Critical Care Medicine, Kunshan Hostipal Affiliated to Jiangsu University, Suzhou Jiangsu 215300, China)
Abstract： Objective： To investigate the expression level and clinical significance of potassium voltage-gated channel subfamily G member 1 (KCNG1) in human lung cancer tissues, and its role in the malignant biological behavior of lung cancer cells. Methods: The Cancer Genome Atlas (TCGA) database was consulted to explore the expression level of KCNG1 mRNA in human lung cancers, and the relationship between KCNG1 mRNA and clinicopathological features and prognosis of patients with lung cancer; nomogram model was constructed to predict the prognosis of lung cancer patients based on the KCNG1 mRNA expression; Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to explore the potential biological functions of KCNG1; gene set enrichment analysis (GSEA) was employed to analyze the differentially expressed genes, through comparing KCNG1 high-expression lung cancer tissues with the KCNG1 low-expression lung cancer tissues retrieved from TCGA database. The expression level of KCNG1 mRNA and protein in lung cancer A549 and H1299 cell lines and normal lung epithelial cells were detected by Western blotting and qRT-PCR assays, respectively. The KCNG1 knockdown cell lines were constructed by transfection of siRNA, and the biological behavior changes of the cell lines were detected by EdU, Transwell, Matrigel Transwell, scratch wound healing and angiogenesis mimicry tests, respectively. Results: The expression of KCNG1 mRNA was significantly upregulated in human lung cancer tissues and was correlated with poor prognosis of lung cancer patients (P<0.05). The nomogram model preliminarily confirmed that KCNG1 may be a potential biomarker of lung cancer and has a good prognostic function. GO and KEGG enrichment analysis suggested that KCNG1 plays an important role in regulating hormone secretion, ion transportation, neuropeptide signaling pathway, and intercellular adhesion. GSEA showed that KCNG1 related differentially expressed genes were enriched in KRAS, MTORC1, MYC, P53, and WNT signaling pathways. The proliferation, migration, invasion and tube formation of si-KCNG1 lung cancer cells were significantly inhibited (P<0.05). Conclusion: The expression of KCNG1 mRNA is significantly overexpressed in lung cancer and is closely related to poor prognosis. SiRNA-mediated knockdown of KCNG1 could significantly inhibit the malignant behaviors of lung cancer cell.
［Key words］lung cancer; potassium voltagegated channel modifier subfamily G member 1; molecular therapeutic target; differentially expressed genes; biomarkers
