基于高通量转录组探索CCNB1、ASPM在糖尿病足溃疡治疗的应用
Exploring the Application of CCNB1 and ASPM in the Treatment of Diabetes Foot Ulcer Based on High-Throughput Transcriptome
DOI: 10.12677/acm.2024.1461867, PDF,   
作者: 阎复利*:保定泰和康复医院护理部,河北 保定;楚俞君*:中国医学科学院北京协和医学院护理学院,北京;高永昌#:河北易县中医医院外科,河北 保定
关键词: 糖尿病足溃疡分子机制差异表达基因靶点基因Diabetic Foot Ulcer Molecular Mechanisms Differentially Expressed Genes Target Genes
摘要: 背景:糖尿病足溃疡是糖尿病患者常见的并发症,其危害性不容小觑,然而其分子机制尚不完全清楚。方法:利用GEO数据库中的糖尿病足溃疡数据集GSE143735,通过limma包筛选差异表达基因(DEGs),并进行功能富集分析和GSEA。利用WGCNA构建共表达网络,筛选重要模块,再通过STRING数据库构建PPI网络。通过Cytoscape可视化并获取靶点基因。通过基因表达量热图展示核心基因在糖尿病足溃疡和正常样本中的表达差异。miRNA预测网站用于找出调节靶点基因的miRNA。结果:发现了1778个差异表达基因。功能富集分析表明这些基因主要涉及伤口愈合、细胞连接等生物学过程。WGCNA和PPI网络分析鉴定了CCNB1和ASPM等核心基因,并通过热图展示其在疾病样本中的低表达。miRNA预测进一步揭示了这些基因在糖尿病足溃疡中的潜在作用。结论:CCNB1和ASPM在糖尿病足溃疡中低表达,它们可能在糖尿病足溃疡的发展中发挥重要作用。
Abstract: Background: Diabetic foot ulcer (DFU) is a common complication in diabetic patients, posing significant health risks. However, its molecular mechanisms remain incompletely understood. Methods: The diabetic foot ulcer dataset GSE143735 from the GEO database was utilized for differential gene expression analysis using the limma package, followed by functional enrichment analysis and Gene Set Enrichment Analysis (GSEA). Weighted Gene Co-expression Network Analysis (WGCNA) was employed to construct co-expression networks and identify key modules, followed by Protein-Protein Interaction (PPI) network construction using the STRING database. Visualize and obtain target genes through Cytoscape. The differential expression of core genes in diabetes foot ulcer and normal samples was demonstrated by gene expression calorimetry. miRNA prediction websites were utilized to identify miRNAs regulating core genes. Results: A total of 1778 differentially expressed genes were identified. Functional enrichment analysis revealed involvement of these genes in biological processes such as wound healing and cell adhesion. WGCNA and PPI network analysis identified core genes CCNB1 and ASPM, and demonstrated their low expression in disease samples through heatmaps. While miRNA prediction further elucidated their potential roles in diabetic foot ulcers. Conclusions: CCNB1 and ASPM are down regulated in diabetic foot ulcers, suggesting their potential importance in the development of this condition.
文章引用:阎复利, 楚俞君, 高永昌. 基于高通量转录组探索CCNB1、ASPM在糖尿病足溃疡治疗的应用[J]. 临床医学进展, 2024, 14(6): 963-974. https://doi.org/10.12677/acm.2024.1461867

参考文献

[1] American Diabetes Association (2008) Economic Costs of Diabetes in the U.S. in 2007. Diabetes Care, 31, 596-615. [Google Scholar] [CrossRef] [PubMed]
[2] Boulton, A.J., Vileikyte, L., Ragnarson-Tennvall, G. and Apelqvist, J. (2005) The Global Burden of Diabetic Foot Disease. The Lancet, 366, 1719-1724. [Google Scholar] [CrossRef] [PubMed]
[3] Gregg, E.W., Li, Y., Wang, J., Rios Burrows, N., Ali, M.K., Rolka, D., et al. (2014) Changes in Diabetes-Related Complications in the United States, 1990-2010. New England Journal of Medicine, 370, 1514-1523. [Google Scholar] [CrossRef] [PubMed]
[4] Ahmed, A.S. and Antonsen, E.L. (2016) Immune and Vascular Dysfunction in Diabetic Wound Healing. Journal of Wound Care, 25, S35-S46. [Google Scholar] [CrossRef] [PubMed]
[5] Falanga, V. (2005) Wound Healing and Its Impairment in the Diabetic Foot. The Lancet, 366, 1736-1743. [Google Scholar] [CrossRef] [PubMed]
[6] Davis, F.M., Kimball, A., Boniakowski, A. and Gallagher, K. (2018) Dysfunctional Wound Healing in Diabetic Foot Ulcers: New Crossroads. Current Diabetes Reports, 18, Article No. 2. [Google Scholar] [CrossRef] [PubMed]
[7] Pitocco, D., Spanu, T., Di Leo, M., et al. (2019) Diabetic Foot Infections: A Comprehensive Overview. European Review for Medical and Pharmacological Sciences, 23, 26-37.
[8] Gherman, D., Dumitrescu, C.I., Ciocan, A. and Melincovici, C.S. (2018) Histopathological Changes in Major Amputations Due to Diabetic Foot—A Review. Romanian Journal of Morphology and Embryology, 59, 699-702.
[9] Armstrong, D.G., Swerdlow, M.A., Armstrong, A.A., Conte, M.S., Padula, W.V. and Bus, S.A. (2020) Five Year Mortality and Direct Costs of Care for People with Diabetic Foot Complications Are Comparable to Cancer. Journal of Foot and Ankle Research, 13, 16. [Google Scholar] [CrossRef] [PubMed]
[10] Zhang, Y., Zhu, T., He, F., Chen, A.C., Yang, H. and Zhu, X. (2021) Identification of Key Genes and Pathways in Osteoarthritis via Bioinformatic Tools: An Updated Analysis. CARTILAGE, 13, 1457S-1464S. [Google Scholar] [CrossRef] [PubMed]
[11] Canzoneri, R., Lacunza, E. and Abba, M.C. (2019) Genomics and Bioinformatics as Pillars of Precision Medicine in Oncology. Medicina, 79, 587-592.
[12] Merrick, B.A., London, R.E., Bushel, P.R., Grissom, S.F. and Paules, R.S. (2011) Platforms for Biomarker Analysis Using High-Throughput Approaches in Genomics, Transcriptomics, Proteomics, Metabolomics, and Bioinformatics. IARC Scientific Publications, 163, 121-142.
[13] Nie, X., Zhao, J., Ling, H., Deng, Y., Li, X. and He, Y. (2020) Exploring microRNAs in Diabetic Chronic Cutaneous Ulcers: Regulatory Mechanisms and Therapeutic Potential. British Journal of Pharmacology, 177, 4077-4095. [Google Scholar] [CrossRef] [PubMed]
[14] Skyler, J.S., Bakris, G.L., Bonifacio, E., Darsow, T., Eckel, R.H., Groop, L., et al. (2016) Differentiation of Diabetes by Pathophysiology, Natural History, and Prognosis. Diabetes, 66, 241-255. [Google Scholar] [CrossRef] [PubMed]
[15] Petrachkova, T., Wortinger, L.A., Bard, A.J., Singh, J., Warga, R.M. and Kane, D.A. (2019) Lack of Cyclin B1 in Zebrafish Causes Lengthening of G2 and M Phases. Developmental Biology, 451, 167-179. [Google Scholar] [CrossRef] [PubMed]
[16] Pines, J. (1993) Cyclins and Cyclin-Dependent Kinases: Take Your Partners. Trends in Biochemical Sciences, 18, 195-197. [Google Scholar] [CrossRef] [PubMed]
[17] Malumbres, M. and Barbacid, M. (2005) Mammalian Cyclin-Dependent Kinases. Trends in Biochemical Sciences, 30, 630-641. [Google Scholar] [CrossRef] [PubMed]
[18] Zhang, H., Zhang, X., Li, X., Meng, W., Bai, Z., Rui, S., et al. (2018) Effect of CCNB1 Silencing on Cell Cycle, Senescence, and Apoptosis through the p53 Signaling Pathway in Pancreatic Cancer. Journal of Cellular Physiology, 234, 619-631. [Google Scholar] [CrossRef] [PubMed]
[19] Oropeza-Valdez, J.J., Hernandez, J., Jaime-Sánchez, E., López-Ramos, E., Lara-Ramírez, E.E., Hernández, Y.L., et al. (2023) Transcriptome Analysis Identifies Oxidative Stress Injury Biomarkers for Diabetic Nephropathy. Archives of Medical Research, 54, 17-26. [Google Scholar] [CrossRef] [PubMed]
[20] Jin, Y. and Wang, H. (2023) Identification of Hub Genes Affecting Gestational Diabetes Mellitus Based on GEO Database. Biotechnology and Genetic Engineering Reviews. [Google Scholar] [CrossRef] [PubMed]
[21] Lin, Y., Wang, F., Cheng, L., Fang, Z. and Shen, G. (2021) Identification of Key Biomarkers and Immune Infiltration in Sciatic Nerve of Diabetic Neuropathy BKS-db/db Mice by Bioinformatics Analysis. Frontiers in Pharmacology, 12, Article 682005. [Google Scholar] [CrossRef] [PubMed]
[22] Zhu, H.-J., Fan, M. and Gao, W. (2021) Identification of Potential Hub Genes Associated with Skin Wound Healing Based on Time Course Bioinformatic Analyses. BMC Surgery, 21, Article No. 303. [Google Scholar] [CrossRef] [PubMed]
[23] Niméus-Malmström, E., Koliadi, A., Ahlin, C., Holmqvist, M., Holmberg, L., Amini, R.-M., et al. (2010) Cyclin B1 Is a Prognostic Proliferation Marker with a High Reproducibility in a Population-Based Lymph Node Negative Breast Cancer Cohort. International Journal of Cancer, 127, 961-967. [Google Scholar] [CrossRef] [PubMed]
[24] Bond, J., Roberts, E., Mochida, G.H., Hampshire, D.J., Scott, S., Askham, J.M., et al. (2002) ASPM Is a Major Determinant of Cerebral Cortical Size. Nature Genetics, 32, 316-320. [Google Scholar] [CrossRef] [PubMed]
[25] Bikeye, S.N., Colin, C., Marie, Y., Vampouille, R., Ravassard, P., Rousseau, A., et al. (2010) ASPM-Associated Stem Cell Proliferation Is Involved in Malignant Progression of Gliomas and Constitutes an Attractive Therapeutic Target. Cancer Cell International, 10, Article No. 1. [Google Scholar] [CrossRef] [PubMed]
[26] Buchman, J.J., Durak, O. and Tsai, L. (2011) ASPM Regulates Wnt Signaling Pathway Activity in the Developing Brain. Genes & Development, 25, 1909-1914. [Google Scholar] [CrossRef] [PubMed]
[27] Pierzak-Sominka, J., Skonieczna-Żydecka, K., Rudnicki, J. and Karakiewicz, B. (2016) The Impact of rs3762271 and rs930557 Polymorphisms of ASPM and MCPH1 Genes on the Anatomy and Function of the Brain. Biological Research for Nursing, 18, 386-393. [Google Scholar] [CrossRef] [PubMed]
[28] Zhou, J.W., Wang, H., Sun, W., Han, N.N. and Chen, L. (2020) ASPM Is a Predictor of Overall Survival and Has Therapeutic Potential in Endometrial Cancer. American Journal of Translational Research, 12, 1942-1953.
[29] Priya, A., Dashti, M., Thanaraj, T.A., Irshad, M., Singh, V., Tandon, R., et al. (2024) Identification of Potential Regulatory Mechanisms and Therapeutic Targets for Lung Cancer. Journal of Biomolecular Structure and Dynamics. [Google Scholar] [CrossRef] [PubMed]
[30] Horvath, S., Zhang, B., Carlson, M., Lu, K.V., Zhu, S., Felciano, R.M., et al. (2006) Analysis of Oncogenic Signaling Networks in Glioblastoma Identifies ASPM as a Molecular Target. Proceedings of the National Academy of Sciences, 103, 17402-17407. [Google Scholar] [CrossRef] [PubMed]
[31] Wu, J., He, Z., Zhu, Y., Jiang, C., Deng, Y. and Wei, B. (2021) ASPM Predicts Poor Clinical Outcome and Promotes Tumorigenesis for Diffuse Large B-Cell Lymphoma. Current Cancer Drug Targets, 21, 80-89. [Google Scholar] [CrossRef] [PubMed]