2. Academic Validation
  3. Anti-NSCLC role of SCN4B by negative regulation of the cGMP-PKG pathway: Integrated utilization of bioinformatics analysis and in vitro assay validation

Anti-NSCLC role of SCN4B by negative regulation of the cGMP-PKG pathway: Integrated utilization of bioinformatics analysis and in vitro assay validation

  • Drug Dev Res. 2024 May;85(3):e22192. doi: 10.1002/ddr.22192.
Xiujun Yang 1,  Qun Liu 2,  Gang Li 3
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, Huai'an People's Hospital of Hongze District, Huai'an, China.
  • 2 Medical Ward 20, Lianshui County People's Hospital, Huai'an, China.
  • 3 Department of Respiratory and Critical Care Medicine, Huai'an Second People's Hospital, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.
PMID: 38678552 DOI: 10.1002/ddr.22192
Abstract

Non-small cell lung Cancer (NSCLC) is a malignant tumor with low overall cure and survival rates. Uncovering abnormally expressed genes is significantly important for developing novel targeted therapies in NSCLC. This study aimed to discover new differentially expressed genes (DEGs) of NSCLC. The DEGs of NSCLC were identified in eight data sets from Gene Expression Omnibus (GEO) database. The expression profiles and the prognostic significance of SCN4B in LUAD and LUSC were analyzed using GEPIA database. LinkedOmics was used to identify co-expressed genes with SCN4B, which were further subjected to KEGG pathway enrichment analysis. SCN4B-overexpressing plasmid (pcDNA/SCN4B) was transfected into A549 and NCI-H2170 cells to elevate the expression of SCN4B. MTT and TUNEL assays were performed to evaluate cell viability and Apoptosis. Relying on the screened DEGs from GEO database, we identified that SCN4B was significantly downregulated in LUAD and LUSC. We confirmed the downregulation of SCN4B in NSCLC tissues using GEPIA database. SCN4B has a prognostic value in LUAD, but not LUSC. KEGG pathway enrichment analysis of SCN4B-related genes showed that cGMP-PKG signaling pathway might be involved in the role of SCN4B in NSCLC. Overexpression of SCN4B in A549 and NCI-H2170 cells inhibited the cell viability. Besides, SCN4B overexpression induced Apoptosis of A549 and NCI-H2170 cells. SCN4B inhibited the expression of PKG1 and p-CREB in NSCLC cells. Moreover, the inhibitory effects of SCN4B on tumor malignancy were attenuated by the activator of PKG. In conclusion, integrated bioinformatical analysis proved that SCN4B was downregulated and had a prognostic significance in NSCLC. In vitro experimental studies demonstrated that SCN4B regulated NSCLC cells viability and Apoptosis via inhibiting cGMP-PKG signaling pathway.

Keywords

SCN4B; bioinformatical analysis; cGMP‐PKG; differentially expressed genes; non‐small cell lung cancer.

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