دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: Anti-NSCLC role of SCN4B by negative regulation of the cGMP-PKG pathway: Integrated utilization of bioinformatics analysis and in vitro assay validation.
المؤلفون: Yang X; Department of Respiratory and Critical Care Medicine, Huai'an People's Hospital of Hongze District, Huai'an, China., Liu Q; Medical Ward 20, Lianshui County People's Hospital, Huai'an, China., Li G; 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.
المصدر: Drug development research [Drug Dev Res] 2024 May; Vol. 85 (3), pp. e22192.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-Liss Country of Publication: United States NLM ID: 8204468 Publication Model: Print Cited Medium: Internet ISSN: 1098-2299 (Electronic) Linking ISSN: 02724391 NLM ISO Abbreviation: Drug Dev Res Subsets: MEDLINE
أسماء مطبوعة: Publication: New York Ny : Wiley-Liss
Original Publication: New York : Alan R. Liss, c1981-
مواضيع طبية MeSH: Carcinoma, Non-Small-Cell Lung*/genetics , Carcinoma, Non-Small-Cell Lung*/metabolism , Carcinoma, Non-Small-Cell Lung*/pathology , Computational Biology* , Cyclic GMP*/metabolism , Lung Neoplasms*/genetics , Lung Neoplasms*/metabolism , Lung Neoplasms*/pathology, Humans ; A549 Cells ; Apoptosis ; Cell Line, Tumor ; Cell Survival ; Cyclic GMP-Dependent Protein Kinases/metabolism ; Cyclic GMP-Dependent Protein Kinases/genetics ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; Signal Transduction
مستخلص: 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.
(© 2024 Wiley Periodicals LLC.)
References: Bai, M., Ke, S., Yu, H., Xu, Y., Yu, Y., Lu, S., Wang, C., Huang, J., Ma, Y., Dai, W., & Wu, Y. (2022). Key molecules associated with thyroid carcinoma prognosis: A study based on transcriptome sequencing and GEO datasets. Frontiers in Immunology, 13, 964891. https://doi.org/10.3389/fimmu.2022.964891.
Barrett, T., & Edgar, R. (2006). Gene expression omnibus: Microarray data storage, submission, retrieval, and analysis. Methods in Enzymology, 411, 352–369. https://doi.org/10.1016/S0076-6879(06)11019-8.
Barrett, T., Wilhite, S. E., Ledoux, P., Evangelista, C., Kim, I. F., Tomashevsky, M., Marshall, K. A., Phillippy, K. H., Sherman, P. M., Holko, M., Yefanov, A., Lee, H., Zhang, N., Robertson, C. L., Serova, N., Davis, S., & Soboleva, A. (2012). NCBI GEO: Archive for functional genomics data sets‐‐update. Nucleic Acids Research, 41(Database issue), D991–D995. https://doi.org/10.1093/nar/gks1193.
Bon, E., Driffort, V., Gradek, F., Martinez‐Caceres, C., Anchelin, M., Pelegrin, P., Cayuela, M. L., Marionneau‐Lambot, S., Oullier, T., Guibon, R., Fromont, G., Gutierrez‐Pajares, J. L., Domingo, I., Piver, E., Moreau, A., Burlaud‐Gaillard, J., Frank, P. G., Chevalier, S., Besson, P., & Roger, S. (2016). SCN4B acts as a metastasis‐suppressor gene preventing hyperactivation of cell migration in breast cancer. Nature Communications, 7, 13648. https://doi.org/10.1038/ncomms13648.
Bouza, A. A., & Isom, L. L. (2018). Voltage‐gated sodium channel β subunits and their related diseases. Handbook of Experimental Pharmacology, 246, 423–450. https://doi.org/10.1007/164_2017_48.
Browning, D. D., Kwon, I. K., & Wang, R. (2010). cGMP‐dependent protein kinases as potential targets for colon cancer prevention and treatment. Future Medicinal Chemistry, 2(1), 65–80. https://doi.org/10.4155/fmc.09.142.
Bu, D., Luo, H., Huo, P., Wang, Z., Zhang, S., He, Z., Wu, Y., Zhao, L., Liu, J., Guo, J., Fang, S., Cao, W., Yi, L., Zhao, Y., & Kong, L. (2021). KOBAS‐i: Intelligent prioritization and exploratory visualization of biological functions for gene enrichment analysis. Nucleic Acids Research, 49(W1), W317–W325. https://doi.org/10.1093/nar/gkab447.
Clough, E., & Barrett, T. (2016). The Gene Expression Omnibus Database. Methods in Molecular Biology, 1418, 93–110. https://doi.org/10.1007/978-1-4939-3578-9_5.
Dai, W., Zhou, J., Wang, H., Zhang, M., Yang, X., & Song, W. (2020). miR‐424‐5p promotes the proliferation and metastasis of colorectal cancer by directly targeting SCN4B. Pathology ‐ Research and Practice, 216(1), 152731. https://doi.org/10.1016/j.prp.2019.152731.
Duma, N., Santana‐Davila, R., & Molina, J. R. (2019). Non–small cell lung cancer: Epidemiology, screening, diagnosis, and treatment. Mayo Clinic Proceedings, 94(8), 1623–1640. https://doi.org/10.1016/j.mayocp.2019.01.013.
Fallahian, F., Karami‐Tehrani, F., Salami, S., & Aghaei, M. (2011). Cyclic GMP induced apoptosis via protein kinase G in oestrogen receptor‐positive and ‐negative breast cancer cell lines. The FEBS Journal, 278(18), 3360–3369. https://doi.org/10.1111/j.1742-4658.2011.08260.x.
Gong, L., Lei, Y., Tan, X., Dong, Y., Luo, Z., Zhang, D., & Han, S. (2019). Propranolol selectively inhibits cervical cancer cell growth by suppressing the cGMP/PKG pathway. Biomedicine & Pharmacotherapy, 111, 1243–1248. https://doi.org/10.1016/j.biopha.2019.01.027.
Gong, Y., Yang, J., Wu, W., Liu, F., Su, A., Li, Z., Zhu, J., & Wei, T. (2018). Preserved SCN4B expression is an independent indicator of favorable recurrence‐free survival in classical papillary thyroid cancer. PLoS One, 13(5), e0197007. https://doi.org/10.1371/journal.pone.0197007.
Gridelli, C., Rossi, A., Carbone, D. P., Guarize, J., Karachaliou, N., Mok, T., Petrella, F., Spaggiari, L., & Rosell, R. (2015). Non‐small‐cell lung cancer. Nature Reviews Disease Primers, 1, 15009. https://doi.org/10.1038/nrdp.2015.9.
Herbst, R. S., Morgensztern, D., & Boshoff, C. (2018). The biology and management of non‐small cell lung cancer. Nature, 553(7689), 446–454. https://doi.org/10.1038/nature25183.
Jin, X., Guan, Y., Zhang, Z., & Wang, H. (2020). Microarray data analysis on gene and miRNA expression to identify biomarkers in non‐small cell lung cancer. BMC Cancer, 20(1), 329. https://doi.org/10.1186/s12885-020-06829-x.
Jonna, S., & Subramaniam, D. S. (2019). Molecular diagnostics and targeted therapies in non‐small cell lung cancer (NSCLC): An update. Discovery medicine, 27(148), 167–170.
Kong, X., Wang, J. S., & Yang, H. (2021). Upregulation of lncRNA DARS‐AS1 accelerates tumor malignancy in cervical cancer by activating cGMP‐PKG pathway. Journal of Biochemical and Molecular Toxicology, 35(6), 1–11. https://doi.org/10.1002/jbt.22749.
Li, W., Yin, X., Yan, Y., Liu, C., & Li, G. (2021). STEAP4 knockdown inhibits the proliferation of prostate cancer cells by activating the cGMP‐PKG pathway under lipopolysaccharide‐induced inflammatory microenvironment. International Immunopharmacology, 101(Pt B), 108311. https://doi.org/10.1016/j.intimp.2021.108311.
Liu, X., Liu, X., Li, J., & Ren, F. (2019). Identification and integrated analysis of key biomarkers for diagnosis and prognosis of non‐small cell lung cancer. Medical Science Monitor, 25, 9280–9289. https://doi.org/10.12659/MSM.918620.
Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real‐time quantitative PCR and the 2− ΔΔCT method. Methods, 25(4), 402–408. https://doi.org/10.1006/meth.2001.1262.
Lv, Y., Wang, X., Li, X., Xu, G., Bai, Y., Wu, J., Piao, Y., Shi, Y., Xiang, R., & Wang, L. (2020). Nucleotide de novo synthesis increases breast cancer stemness and metastasis via cGMP‐PKG‐MAPK signaling pathway. PLoS Biology, 18(11), e3000872. https://doi.org/10.1371/journal.pbio.3000872.
O'Malley, H. A., & Isom, L. L. (2015). Sodium channel β subunits: Emerging targets in channelopathies. Annual Review of Physiology, 77, 481–504. https://doi.org/10.1146/annurev-physiol-021014-071846.
Piazza, G. A., Ward, A., Chen, X., Maxuitenko, Y., Coley, A., Aboelella, N. S., Buchsbaum, D. J., Boyd, M. R., Keeton, A. B., & Zhou, G. (2020). PDE5 and PDE10 inhibition activates cGMP/PKG signaling to block Wnt/β‐catenin transcription, cancer cell growth, and tumor immunity. Drug Discovery Today, 25(8), 1521–1527. https://doi.org/10.1016/j.drudis.2020.06.008.
Sankar, K., Gadgeel, S. M., & Qin, A. (2020). Molecular therapeutic targets in non‐small cell lung cancer. Expert Review of Anticancer Therapy, 20(8), 647–661. https://doi.org/10.1080/14737140.2020.1787156.
Seo, M. S., Jung, K. H., Kim, K., Lee, J. E., Han, B. S., Ko, S., Kim, J. H., Hong, S., Lee, S. H., & Hong, S. S. (2022). Discovery of a novel NUAK1 inhibitor against pancreatic cancer. Biomedicine & Pharmacotherapy, 152, 113241. https://doi.org/10.1016/j.biopha.2022.113241.
Tang, Z., Li, C., Kang, B., Gao, G., Li, C., & Zhang, Z. (2017). GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Research, 45(W1), W98–W102. https://doi.org/10.1093/nar/gkx247.
Vasaikar, S. V., Straub, P., Wang, J., & Zhang, B. (2018). LinkedOmics: Analyzing multi‐omics data within and across 32 cancer types. Nucleic Acids Research, 46(D1), D956–D963. https://doi.org/10.1093/nar/gkx1090.
Wang, G., Jia, Y., Ye, Y., Kang, E., Chen, H., Wang, J., & He, X. (2021). Identification of key methylation differentially expressed genes in posterior fossa ependymoma based on epigenomic and transcriptome analysis. Journal of Translational Medicine, 19(1), 174. https://doi.org/10.1186/s12967-021-02834-1.
Wang, K., Chen, R., Feng, Z., Zhu, Y. M., Sun, X. X., Huang, W., & Chen, Z. N. (2019). Identification of differentially expressed genes in non‐small cell lung cancer. Aging, 11(23), 11170–11185. https://doi.org/10.18632/aging.102521.
Wang, Y., Fang, J., Zeng, H. F., Zhong, J. F., Li, H. X., & Chen, K. L. (2022). Identification and bioinformatics analysis of differentially expressed milk exosomal microRNAs in milk exosomes of heat‐stressed Holstein cows. Functional & Integrative Genomics, 22(1), 77–87. https://doi.org/10.1007/s10142-021-00814-8.
Wang, Z., Zhang, C., Chang, J., Tian, X., Zhu, C., & Xu, W. (2020). LncRNA EMX2OS, regulated by TCF12, interacts with FUS to regulate the proliferation, migration and invasion of prostate cancer cells through the cGMP‐PKG signaling pathway. OncoTargets and Therapy, 13, 7045–7056. https://doi.org/10.2147/OTT.S243552.
Wong, J. C., Bathina, M., & Fiscus, R. R. (2012). Cyclic GMP/protein kinase G type‐Iα (PKG‐Iα) signaling pathway promotes CREB phosphorylation and maintains higher c‐IAP1, livin, survivin, and Mcl‐1 expression and the inhibition of PKG‐Iα kinase activity synergizes with cisplatin in non‐small cell lung cancer cells. Journal of Cellular Biochemistry, 113(11), 3587–3598. https://doi.org/10.1002/jcb.24237.
Wu, Z., Hui, X., Huo, L., Sun, D., Peng, W., Zhang, Y., Li, X., Ma, T., Li, W., Liang, J., & Sun, Z. (2022). Antiproliferative effects of isoalantolactone in human liver cancer cells are mediated through caspase‐dependent apoptosis, ROS generation, suppression of cell migration and invasion and targeting Ras/Raf/MEK signalling pathway. Acta Biochimica Polonica, 69(2), 299–304. https://doi.org/10.18388/abp.2020_5704.
Yassemi, A., Kashanian, S., & Zhaleh, H. (2020). Folic acid receptor‐targeted solid lipid nanoparticles to enhance cytotoxicity of letrozole through induction of caspase‐3 dependent‐apoptosis for breast cancer treatment. Pharmaceutical Development and Technology, 25(4), 397–407. https://doi.org/10.1080/10837450.2019.1703739.
Yin, Y., Wu, S., Niu, L., & Huang, S. (2023). Protective mechanism of TCF7L1 against retinal photoreceptor cell injury following retinitis pigmentosa based on the GEO database. The FASEB Journal, 37(5), e22885. https://doi.org/10.1096/fj.202201737RR.
Yu, H., Gu, D., & Qian, P. (2020). Prognostic value of ESR2 expression on adjuvant chemotherapy in completely resected NSCLC. PLoS One, 15(12), e0243891. https://doi.org/10.1371/journal.pone.0243891.
Yu, H., Pang, Z., Li, G., & Gu, T. (2021). Bioinformatics analysis of differentially expressed miRNAs in non‐small cell lung cancer. Journal of Clinical Laboratory Analysis, 35(2), e23588. https://doi.org/10.1002/jcla.23588.
فهرسة مساهمة: Keywords: SCN4B; bioinformatical analysis; cGMP‐PKG; differentially expressed genes; non‐small cell lung cancer
المشرفين على المادة: H2D2X058MU (Cyclic GMP)
EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinases)
0 (SCN4B protein, human)
تواريخ الأحداث: Date Created: 20240428 Date Completed: 20240428 Latest Revision: 20240507
رمز التحديث: 20240508
DOI: 10.1002/ddr.22192
PMID: 38678552
قاعدة البيانات: MEDLINE
الوصف
تدمد:1098-2299
DOI:10.1002/ddr.22192