乙肝病毒与类风湿性关节炎关键基因的筛选鉴定
Screening and Identification of Key Genesfor HBV and RA
DOI: 10.12677/ACM.2024.141268, PDF,    国家自然科学基金支持
作者: 赵娜, 王洪星, 张义*:山东大学齐鲁医院检验科,山东济南;张小钰:中国人民解放军联勤保障部队第九六〇医院检验科,山东济南
关键词: 乙型肝炎病毒类风湿性关节炎生物信息学MLF2TRAFD1Hepatitis B Virus Rheumatoid Arthritis Bioinformatics MLF2 TRAFD1
摘要: 目的:探究乙肝病毒(HBV)与类风湿性关节炎(RA)的共同基因特性。方法:在GEO综合数据库获得HBV 和RA基因芯片数据。采用加权基因共表达网络分析(WGCNA)鉴定HBV和RA相关的共表达模块,并利用 GO进行富集信号通路分析。利用验证队列筛选差异基因。通过免疫组化(IHC)和免疫荧光(IF)的方法对 HBV合并RA患者外周血单个核细胞样本中关键基因进行验证。结果:利用WGCNA筛选出HBV患者和RA 患者外周血中44个共享基因。通过GO分析发现,共享基因富集在锌离子结合、I-kappaB激酶/NF-kappaB 激酶、外源性细胞凋亡的正调控等信号通路。差异分析显示,DYNLT1、GRIPAP1、kiAA2013、MLF2 和TRAFD1在HBV和RA组中均上调。IHC和IF结果显示,与对照组相比,MLF2和TRAFD1表达显著上调, 差异有统计学意义(p < 0.05)。结论:MLF2和TRAFD1可能是HBV与RA的关键基因,这为HBV合并RA 的发病机制、新型生物标志物和潜在靶点的研究提供了参考。
Abstract: Objective: This study aims to identify common genetic characteristics between hepatitis B virus (HBV) and rheumatoid arthritis (RA). Methods: HBV and RA gene chip data were obtained from the GEO comprehensive database. Weighted gene co-expression network analysis (WGCNA) was conducted to identify co-expression modules related to HBV and RA, and GO analysis was used for enrichment signaling pathway analysis. Differential gene screening was performed using a validation cohort. The key genes in peripheral blood mononuclear cell samples of patients with HBV and RA were verified using immunohistochemistry (IHC) and immunofluorescence (IF). Results: WGCNA identified 44 shared genes in the peripheral blood of HBV patients and RA patients. GO analysis revealed that these shared genes were enriched in signaling pathways such as zinc ion binding, I-kappaB kinase/NF-kappaB kinase, and positive regulation of exogenous apoptosis. Differential analysis showed that DYNLT1, GRIPAP1, kiAA2013, MLF2, and TRAFD1 were up-regulated in both the HBV and RA groups. IHC and IF results demonstrated a significant up-regulation of MLF2 and TRAFD1 expression compared to the control group (p < 0.05). Conclusion: MLF2 and TRAFD1 may serve as key genes linking HBV and RA, providing valuable insights for studying the pathogenesis, identifying new biomarkers, and potential targets for HBV combined with RA.
文章引用:赵娜, 张小钰, 王洪星, 张义. 乙肝病毒与类风湿性关节炎关键基因的筛选鉴定[J]. 临床医学进展, 2024, 14(1): 1898-1907. https://doi.org/10.12677/ACM.2024.141268

参考文献

[1] Mak, L.Y., et al. (2021) HBV RNA Profiles in Patients with Chronic Hepatitis B under Different Disease Phases and Anti-viral Therapy. Hepatology, 73, 2167-2179. [Google Scholar] [CrossRef] [PubMed]
[2] Petri, M., et al. (2021) Compar-ison of the 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology Systemic Lupus Erythematosus Classification Criteria with Two Sets of Earlier Systemic Lupus Erythematosus Classification Cri-teria. Arthritis Care & Research, 73, 1231-1235. [Google Scholar] [CrossRef] [PubMed]
[3] Smith, M.H. and Berman, J.R. (2022) What Is Rheumatoid Arthritis? JAMA, 327, 1194. [Google Scholar] [CrossRef] [PubMed]
[4] Gravallese, E.M. and Firestein, G.S. (2023) Rheumatoid Arthri-tis—Common Origins, Divergent Mechanisms. The New England Journal of Medicine, 388, 529-542. [Google Scholar] [CrossRef
[5] Trépo, C., Chan, H.L. and Lok, A. (2014) Hepatitis B Virus Infec-tion. Lancet, 384, 2053-2063. [Google Scholar] [CrossRef
[6] Saito, M., et al. (2021) Tctex-1 Augments G Pro-tein-Coupled Receptor-Mediated G(s) Signaling by Activating Adenylyl Cyclase. Journal of Pharmacological Sciences, 145, 150-154. [Google Scholar] [CrossRef] [PubMed]
[7] Miao, S., et al. (2023) Identification of DYNLT1 Associated with Proliferation, Relapse, and Metastasis in Breast Cancer. Frontiers in Medicine, 10, Article 1167676. [Google Scholar] [CrossRef] [PubMed]
[8] Li, D.Y., et al. (2022) Sperm flagellar 2 (SPEF2) Is Essential for Sperm Flagellar Assembly in Humans. Asian Journal of Andrology, 24, 359-366. [Google Scholar] [CrossRef] [PubMed]
[9] Huang, L., Wei, B., Zhao, Y., Gong, X. and Chen, L. (2023) DYNLT1 Promotes Mitochondrial Metabolism to Fuel Breast Cancer Development by Inhibiting Ubiquitination Degradation of VDAC1. Molecular Medicine, 29, Article No. 72. [Google Scholar] [CrossRef] [PubMed]
[10] Williamson, S.R., et al. (2020) Report from the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers: III: Molecular Pathology of Kidney Cancer. The American Journal of Sur-gical Pathology, 44, e47-e65. [Google Scholar] [CrossRef
[11] Goodarzi, H., et al. (2016) Modulated Expression of Specific tRNAs Drives Gene Expression and Cancer Progression. Cell, 165, 1416-1427. [Google Scholar] [CrossRef] [PubMed]
[12] Bai, M., Che, Y., Lu, K. and Fu, L. (2020) Analysis of Deubiquiti-nase OTUD5 as a Biomarker and Therapeutic Target for Cervical Cancer by Bioinformatic Analysis. PeerJ, 8, e9146. [Google Scholar] [CrossRef] [PubMed]
[13] Adler, D., et al. (2014) MED15, Encoding a Subunit of the Mediator Com-plex, Is Overexpressed at High Frequency in Castration-Resistant Prostate Cancer. International Journal of Cancer, 135, 19-26. [Google Scholar] [CrossRef] [PubMed]
[14] Zhang, M., Yang, L., Chen, D. and Heisterkamp, N. (2023) Drug-Tolerant Persister B-Cell Precursor Acute Lymphoblastic Leukemia Cells. bioRxiv. [Google Scholar] [CrossRef] [PubMed]
[15] Rampello, A.J., et al. (2020) Torsin ATPase Deficiency Leads to Defects in Nuclear Pore Biogenesis and Sequestration of MLF2. Journal of Cell Biology, 219, e201910185. [Google Scholar] [CrossRef] [PubMed]
[16] Prophet, S.M., et al. (2022) Atypical Nuclear Envelope Condensates Linked to Neurological Disorders Reveal Nucleoporin-Directed Chaperone Activities. Nature Cell Biology, 24, 1630-1641. [Google Scholar] [CrossRef] [PubMed]
[17] Banerjee, M., Datta, M. and Bhattacharyya, N.P. (2017) Modu-lation of Mutant Huntingtin Aggregates and Toxicity by Human Myeloid Leukemia Factors. The International Journal of Biochemistry & Cell Biology, 82, 1-9. [Google Scholar] [CrossRef] [PubMed]
[18] Yan, J., et al. (2020) Black Carp TRAFD1 Restrains MAVS-Mediated Antiviral Signaling during the Innate Immune Activation. Fish & Shellfish Immunology, 103, 66-72. [Google Scholar] [CrossRef] [PubMed]
[19] Witwicka, H., et al. (2015) TRAFD1 (FLN29) Interacts with Plekhm1 and Regulates Osteoclast Acidification and Resorption. PLOS ONE, 10, e0127537. [Google Scholar] [CrossRef] [PubMed]
[20] Yang, J., et al. (2020) The Role of Phosphorylation of MLF2 at Serine 24 in BCR-ABL Leukemogenesis. Cancer Gene Therapy, 27, 98-107. [Google Scholar] [CrossRef] [PubMed]
[21] Fang, D., et al. (2023) MLF2 Negatively Regulates P53 and Promotes Colorectal Carcinogenesis. Advanced Science, 10, e2303336. [Google Scholar] [CrossRef] [PubMed]
[22] Dave, B., et al. (2014) Targeting RPL39 and MLF2 Reduces Tumor Initiation and Metastasis in Breast Cancer by Inhibiting Nitric Oxide Synthase Signaling. Proceedings of the National Academy of Sciences of the United States of America, 111, 8838-8843. [Google Scholar] [CrossRef] [PubMed]
[23] Huang, J.B., Chen, Z.R., Yang, S.L. and Hong, F.F. (2023) Nitric Oxide Synthases in Rheumatoid Arthritis. Molecules, 28, Article 4414. [Google Scholar] [CrossRef] [PubMed]
[24] Guidotti, L.G., McClary, H., Loudis, J.M. and Chisari, F.V. (2000) Nitric Oxide Inhibits Hepatitis B Virus Replication in the Livers of Transgenic Mice. Journal of Experimental Medicine, 191, 1247-1252. [Google Scholar] [CrossRef] [PubMed]
[25] Hsu, J.L., et al. (2013) Zinc-Dependent Interaction between JAB1 and Pre-S2 Mutant Large Surface Antigen of Hepatitis B Virus and Its Implications for Viral Hepatocarcinogenesis. Journal of Virology, 87, 12675-12684. [Google Scholar] [CrossRef
[26] Nováková, J., Talacko, P., Novák, P. and Vališ, K. (2019) The MEK-ERK-MST1 Axis Potentiates the Activation of the Extrinsic Apoptotic Pathway during GDC-0941 Treatment in Jurkat T Cells. Cells, 8, Article 191. [Google Scholar] [CrossRef] [PubMed]
[27] Oh, Y.T. and Sun, S.Y. (2021) Regulation of Cancer Metastasis by TRAIL/Death Receptor Signaling. Biomolecules, 11, Article 499. [Google Scholar] [CrossRef] [PubMed]
[28] Gao, H., et al. (2023) Targeting Ubiquitin Specific Proteases (USPs) in Cancer Immunotherapy: From Basic Research to Pre-clinical Application. Journal of Experimental & Clinical Cancer Research, 42, Article No. 225. [Google Scholar] [CrossRef] [PubMed]
[29] Nanda, S.K., et al. (2011) Polyubiquitin Binding to ABIN1 Is Required to Prevent Autoimmunity. The Journal of Experimental Medicine, 208, 1215-1228. [Google Scholar] [CrossRef] [PubMed]
[30] Luo, X.B., et al. (2020) Proinflammatory Effects of Ubiquitin-Specific Protease 5 (USP5) in Rheumatoid Arthritis Fibroblast-Like Synoviocytes. Mediators of Inflammation, 2020, Article ID: 8295149. [Google Scholar] [CrossRef] [PubMed]