دورية أكاديمية

Identification of SRXN1 and KRT6A as Key Genes in Smoking-Related Non-Small-Cell Lung Cancer Through Bioinformatics and Functional Analyses

التفاصيل البيبلوغرافية
العنوان: Identification of SRXN1 and KRT6A as Key Genes in Smoking-Related Non-Small-Cell Lung Cancer Through Bioinformatics and Functional Analyses
المؤلفون: Jiazhen Zhou, Guanqing Jiang, Enwu Xu, Jiaxin Zhou, Lili Liu, Qiaoyuan Yang
المصدر: Frontiers in Oncology, Vol 11 (2022)
بيانات النشر: Frontiers Media S.A., 2022.
سنة النشر: 2022
المجموعة: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
مصطلحات موضوعية: lung cancer, non-small-cell lung cancer, smoking-related gene, KRT6A, SRXN1, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: BackgroundLung cancer is the leading cause of cancer-related mortality worldwide. Although cigarette smoking is an established risk factor for lung cancer, few reliable smoking-related biomarkers for non-small-cell lung cancer (NSCLC) are available. An improved understanding of these biomarkers would further the development of new biomarker-targeted therapies and lead to improvements in overall patient survival.MethodsWe performed bioinformatic analysis to screened potential target genes, then quantitative PCR, western, siRNA, CCK-8, flow cytometry, tumorigenicity assays in nude mice were performed to validated the function.ResultsIn this study, we identified 83 smoking-related genes (SRGs) based on an integration analysis of two Gene Expression Omnibus (GEO) datasets, and 27 hub SRGs with potential carcinogenic effects by analyzing a dataset of smokers with NSCLC in The Cancer Genome Atlas (TCGA) database. A survival analysis revealed three genes with potential prognostic value, namely SRXN1, KRT6A and JAKMIP3. A univariate Cox analysis revealed significant associations of elevated SRXN1 and KRT6A expression with prognosis. A receiver operating characteristic (ROC) curve analysis indicated the high diagnostic value of SRXN1 and KRT6A for smoking and cancer. Quantitative PCR and western blotting validated the increased expression of SRXN1 and KRT6A mRNA and protein, respectively, in lung cancer cell lines and NSCLC tissues. In patients with NSCLC, SRXN1 and KRT6A expression was associated with the tumor–node–metastasis (TNM) stage, presence of metastasis, history of smoking and daily smoking consumption. Furthermore, inhibition of SRXN1 or KRT6A suppressed viability and enhanced apoptosis in the A549 human lung carcinoma cell line. Tumorigenicity assays in nude mice confirmed that the siRNA-mediated downregulation of SRXN1 and KRT6A expression inhibited tumor growth in vivo.ConclusionsIn summary, SRXN1 and KRT6A act as oncogenes in NSCLC and might be potential biomarkers of smoking exposure and the early diagnosis and prognosis of NSCLC in smokers, which is vital for lung cancer therapy.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2234-943X
العلاقة: https://www.frontiersin.org/articles/10.3389/fonc.2021.810301/fullTest; https://doaj.org/toc/2234-943XTest
DOI: 10.3389/fonc.2021.810301
الوصول الحر: https://doaj.org/article/a3af0aa28c9e4a2d8378e1a2e07fa82bTest
رقم الانضمام: edsdoj.3af0aa28c9e4a2d8378e1a2e07fa82b
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2234943X
DOI:10.3389/fonc.2021.810301