[1]张珍珍,刘一妍,舒 悦,等.基于生物信息学的hsa-miR-155-5p通过PTEN调控中央记忆T细胞/辅助T细胞对肝细胞癌免疫微环境的影响研究[J].医学信息,2024,37(09):7-15.[doi:10.3969/j.issn.1006-1959.2024.09.002]
　ZHANG Zhen-zhen,LIU Yi-yan,SHU Yue,et al.Effect of hsa-miR-155-5p on the Immune Microenvironment of Hepatocellular Carcinoma by Regulating Central Memory T Cells Helper T Cells Through PTEN Based on the Bioinformatics Method[J].Journal of Medical Information,2024,37(09):7-15.[doi:10.3969/j.issn.1006-1959.2024.09.002]
点击复制

基于生物信息学的hsa-miR-155-5p通过PTEN调控中央记忆T细胞/辅助T细胞对肝细胞癌免疫微环境的影响研究()
分享到：

医学信息[ISSN:1006-1959/CN:61-1278/R]

卷:
37卷
期数:
2024年09期
页码:
7-15
栏目:
生物信息学
出版日期:
2024-05-01

文章信息/Info

Title:
Effect of hsa-miR-155-5p on the Immune Microenvironment of Hepatocellular Carcinoma by Regulating Central Memory T Cells Helper T Cells Through PTEN Based on the Bioinformatics Method
文章编号:
1006-1959（2024）09-0007-09
作者:
张珍珍; 刘一妍; 舒 悦; 等
（1.徐州医科大学附属医院东院感染及肝病科，江苏 徐州 221000；2.昆明医科大学第三附属医院神经外科，云南 昆明 650500）
Author(s):
ZHANG Zhen-zhen; LIU Yi-yan; SHU Yue; et al.
(1.Department of Infection and Hepatology,East Hospital Affiliated Hospital of Xuzhou Medical University,Xuzhou 221000,Jiangsu,China; 2.Department of Neurosurgery,the Third Affiliated Hospital of Kunming Medical University,Kunming 650500,Yunnan,China)
关键词:
肝细胞癌; hsa-miR-155-5p; 生物信息学; PTEN; 中央记忆T细胞; 辅助T细胞
Keywords:
Hepatocellular carcinoma; hsa-miR-155-5p; Bioinformatics; PTEN; Central memory T cells; Helper T cells
分类号:
R735.7
DOI:
10.3969/j.issn.1006-1959.2024.09.002
文献标志码:
B
摘要:
目的 运用生物信息学方法预测人类miR-155-5p靶基因，进一步探索其在肝细胞癌（HCC）中的功能。方法 通过starBase数据库筛选出hsa-miR-155-5p靶基因，DAVID和Reactome数据库进行功能富集分析。蛋白-蛋白相互作用网络分析靶基因之间的相互关系，cytohubba插件获得关键基因。Kaplan-Meier生存分析进一步筛选关键基因，ssGSEA 算法分析HCC免疫浸润情况，Spearman相关系数分析关键基因与免疫浸润的相关性。结果 共筛选出1493个hsa-miR-155-5p靶基因；靶基因GO富集分析集中于调控转录、蛋白质分解代谢过程、细胞周期的调节；KEGG生物通路主要富集于AMPK信号通路、PI3K-Akt信号通路和FoxO信号通路、以及子宫内膜癌、胰腺癌和肝细胞癌等疾病通路。利用蛋白互作网络共获得30个关键基因，与HCC信号通路基因取交集获得GSK3B、PTEN、PIK3R1、EGFR、CCND1、SMAD2、PIK3CA、RPS6KB1、KRAS、SOS1 等10个关键基因。生存分析显示，PTEN高表达的HCC患者的预后优于低表达患者。PTEN表达量与中央记忆T细胞、辅助T细胞的免疫浸润均呈现较强的正相关性。结论 hsa-miR-155-5p通过下游靶基因PTEN调控中央记忆T细胞、辅助T细胞，进而影响HCC免疫浸润微环境，或可为HCC发生机制和临床治疗的探索提供帮助。
Abstract:
Objective To predict the target genes of human miR-155-5p by bioinformatics methods, and to further explore its function in hepatocellular carcinoma (HCC).Methods The target genes of hsa-miR-155-5p were screened by starBase database, and functional enrichment analysis was performed by DAVID and Reactome databases. Protein-protein interaction network was used to analyze the relationship between target genes, and cytohubba plug-in was used to obtain key genes. Kaplan-Meier survival analysis was used to further screen key genes, ssGSEA algorithm was used to analyze the immune infiltration of HCC, and Spearman correlation coefficient was used to analyze the correlation between key genes and immune infiltration.Results A total of 1493 hsa-miR-155-5p target genes were screened. GO enrichment analysis of target genes focused on the regulation of transcription, protein catabolic process and cell cycle regulation. The KEGG biological pathway was mainly enriched in AMPK signaling pathway, PI3K-Akt signaling pathway and FoxO signaling pathway, as well as endometrial cancer, pancreatic cancer and hepatocellular carcinoma. A total of 30 key genes were obtained by protein interaction network, and 10 key genes such as GSK3B, PTEN, PIK3R1, EGFR, CCND1, SMAD2, PIK3CA, RPS6KB1, KRAS and SOS1 were obtained by intersection with Hepatocellular carcinoma signaling pathway genes. Survival analysis showed that the prognosis of HCC patients with high expression of PTEN was better than that of patients with low expression. The expression of PTEN was positively correlated with the immune infiltration of central memory T cells and helper T cells.Conclusion hsa-miR-155-5p regulates central memory T cells and helper T cells through the downstream target gene PTEN, thereby affecting the immune infiltration microenvironment of HCC, which may provide help for the exploration of HCC pathogenesis and clinical treatment.

参考文献/References:

[1]Sung H,Ferlay J,Siegel RL,et al.Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J].CA Cancer J Clin,2021,71(3):209-249.[2]Gao YX,Yang TW,Yin JM,et al.Progress and prospects of biomarkers in primary liver cancer (Review)[J].Int J Oncol,2020,57(1):54-66.[3]Hill M,Tran N.miRNA interplay:mechanisms and consequences in cancer[J].Dis Model Mech,2021,14(4):dmm047662.[4]Shu J,Kren BT,Xia Z,et al.Genomewide microRNA down-regulation as a negative feedback mechanism in the early phases of liver regeneration[J].Hepatology,2011,54(2):609-619.[5]Chen X,Murad M,Cui YY,et al.miRNA regulation of liver growth after 50% partial hepatectomy and small size grafts in rats[J].Transplantation,2011,91(3):293-299.[6]Yan-Nan B,Zhao-Yan Y,Li-Xi L,et al.MicroRNA-21 accelerates hepatocyte proliferation in vitro via PI3K/Akt signaling by targeting PTEN[J].Biochem Biophys Res Commun,2014,443(3):802-807.[7]Ning S,Liu H,Gao B,et al.miR-155, miR-96 and miR-99a as potential diagnostic and prognostic tools for the clinical management of hepatocellular carcinoma[J].Oncol Lett,2019,18(3):3381-3387.[8]Fu X,Wen H,Jing L,et al.MicroRNA-155-5p promotes hepatocellular carcinoma progression by suppressing PTEN through the PI3K/Akt pathway[J].Cancer Sci,2017,108(4):620-631.[9]Lin XQ,Huang ZM,Chen X,et al.XIST Induced by JPX Suppresses Hepatocellular Carcinoma by Sponging miR-155-5p[J].Yonsei Med J,2018,59(7):816-826.[10]Szklarczyk D,Gable AL,Nastou KC,et al.The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets[J].Nucleic Acids Res,2021,49(D1):D605-D612.[11]Li B,Severson E,Pignon JC,et al.Comprehensive analyses of tumor immunity: implications for cancer immunotherapy[J].Genome Biol,2016,17(1):174.[12]Pasculli B,Barbano R,Fontana A,et al.Hsa-miR-155-5p Up-Regulation in Breast Cancer and Its Relevance for Treatment With Poly[ADP-Ribose] Polymerase 1 (PARP-1) Inhibitors[J].Front Oncol,2020,10:1415.[13]Soltani I,Bahia W,Farrah A,et al.Potential functions of hsa-miR-155-5p and core genes in chronic myeloid leukemia and emerging role in human cancer:A joint bioinformatics analysis[J].Genomics,2021,113(4):1647-1658.[14]Li S,Zhang T,Zhou X,et al.The tumor suppressor role of miR-155-5p in gastric cancer[J].Oncol Lett,2018,16(2):2709-2714.[15]Cheng J,Zhang Y,Yang J,et al.MiR-155-5p modulates inflammatory phenotype of activated oral lichen-planus-associated-fibroblasts by targeting SOCS1[J].Mol Biol Rep,2022,49(8):7783-7792.[16]Wu YZ,Huang HT,Cheng TL,et al.Application of microRNA in Human Osteoporosis and Fragility Fracture: A Systemic Review of Literatures[J].Int J Mol Sci,2021,22(10):5232.[17]Petejova N,Martinek A,Zadrazil J,et al.Acute Kidney Injury in Septic Patients Treated by Selected Nephrotoxic Antibiotic Agents-Pathophysiology and Biomarkers-A Review[J].Int J Mol Sci,2020,21(19):7115.[18]Bai X,Luo Q,Tan K,et al.Diagnostic value of VDBP and miR-155-5p in diabetic nephropathy and the correlation with urinary microalbumin[J].Exp Ther Med,2020,20(5):86.[19]Wang J,Zhao Q.LncRNA LINC-PINT increases SOCS1 expression by sponging miR-155-5p to inhibit the activation of ERK signaling pathway in rheumatoid arthritis synovial fibroblasts induced by TNF-α[J].Int Immunopharmacol,2020,84:106497.[20]Wang J,Che J.CircTP63 promotes hepatocellular carcinoma progression by sponging miR-155-5p and upregulating ZBTB18[J].Cancer Cell Int,2021,21(1):156.[21]Wu SY,Lan SH,Liu HS.Degradative autophagy selectively regulates CCND1 (cyclin D1) and MIR224, two oncogenic factors involved in hepatocellular carcinoma tumorigenesis[J].Autophagy,2019,15(4):729-730.[22]Ai X,Xiang L,Huang Z,et al.Overexpression of PIK3R1 promotes hepatocellular carcinoma progression[J].Biol Res,2018,51(1):52.[23]Li J,Yen C,Liaw D,et al.PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer[J].Science,1997,275(5308):1943-1947.[24]Mi D,Yi J,Liu E,et al.Relationship between PTEN and VEGF expression and clinicopathological characteristics in HCC[J].J Huazhong Univ Sci Technolog Med Sci,2006,26(6):682-685.[25]Zhu AX,Duda DG,Sahani DV,et al.HCC and angiogenesis: possible targets and future directions[J].Nat Rev Clin Oncol,2011,8(5):292-301.[26]Wang W,Wei C.Advances in the early diagnosis of hepatocellular carcinoma[J].Genes Dis,2020,7(3):308-319.[27]Yilma M,Saxena V,Mehta N.Models to Predict Development or Recurence of Hepatocellular Carcinoma (HCC) in Patients with Advanced Hepatic Fibrosis[J].Curr Gastroenterol Rep,2022,24(1):1-9.[28]Bartel DP.Metazoan MicroRNAs[J].Cell,2018,173(1):20-51.[29]Oura K,Morishita A,Masaki T.Molecular and Functional Roles of MicroRNAs in the Progression of Hepatocellular Carcinoma-A Review[J].Int J Mol Sci,2020,21(21):8362.[30]Xu WD,Feng SY,Huang AF.Role of miR-155 in inflammatory autoimmune diseases: a comprehensive review[J].Inflamm Res,2022,71(12):1501-1517.[31]Elton TS,Selemon H,Elton SM,et al.Regulation of the MIR155 host gene in physiological and pathological processes[J].Gene,2013,532(1):1-12.[32]Higgs G,Slack F.The multiple roles of microRNA-155 in oncogenesis[J].J Clin Bioinforma,2013,3(1):17.[33]Chen G,Wang D,Zhao X,et al.miR-155-5p modulates malignant behaviors of hepatocellular carcinoma by directly targeting CTHRC1 and indirectly regulating GSK-3β-involved Wnt/β-catenin signaling[J].Cancer Cell Int,2017,17:118.[34]Yao Y,Shu F,Wang F,et al.Long noncoding RNA LINC01189 is associated with HCV-hepatocellular carcinoma and regulates cancer cell proliferation and chemoresistance through hsa-miR-155-5p[J].Ann Hepatol,2021,22:100269.[35]Najafi M,Hashemi Goradel N,Farhood B,et al.Macrophage polarity in cancer: A review[J].J Cell Biochem,2019,120(3):2756-2765.[36]Bi L,Ren Y,Feng M,et al.HDAC11 Regulates Glycolysis through the LKB1/AMPK Signaling Pathway to Maintain Hepatocellular Carcinoma Stemness[J].Cancer Res,2021,81(8):2015-2028.[37]Simpson L,Parsons R.PTEN: life as a tumor suppressor[J].Exp Cell Res,2001,264(1):29-41.[38]Worby CA,Dixon JE.PTEN[J].Annu Rev Biochem,2014,83:641-669.[39]Alimonti A,Carracedo A,Clohessy JG,et al.Subtle variations in Pten dose determine cancer susceptibility[J].Nat Genet,2010,42(5):454-458.[40]Doherty DG.Immunity, tolerance and autoimmunity in the liver: A comprehensive review[J].J Autoimmun,2016,66:60-75.[41]Gnyawali B,Pusateri A,Nickerson A,et al.Epidemiologic and socioeconomic factors impacting hepatitis B virus and related hepatocellular carcinoma[J].World J Gastroenterol,2022,28(29):3793-3802.[42]Huang DQ,Mathurin P,Cortez-Pinto H,et al.Global epidemiology of alcohol-associated cirrhosis and HCC: trends, projections and risk factors[J].Nat Rev Gastroenterol Hepatol,2023,20(1):37-49.[43]Stella L,Santopaolo F,Gasbarrini A,et al.Viral hepatitis and hepatocellular carcinoma: From molecular pathways to the role of clinical surveillance and antiviral treatment[J].World J Gastroenterol,2022,28(21):2251-2281.[44]Beier KC,Kallinich T,Hamelmann E.Master switches of T-cell activation and differentiation[J].Eur Respir J,2007,29(4):804-812.[45]Klebanoff CA,Gattinoni L,Restifo NP.Sorting through subsets: which T-cell populations mediate highly effective adoptive immunotherapy?[J].J Immunother,2012,35(9):651-660.[46]Lu Y,Yang A,Quan C,et al.A single-cell atlas of the multicellular ecosystem of primary and metastatic hepatocellular carcinoma[J].Nat Commun,2022,13(1):4594.[47]Sakaguchi E,Kayano K,Segawa M,et al.Th1/Th2 imbalance in HCV-related liver cirrhosis[J].Nihon Rinsho,2001,59(7):1259-1263.[48]Budhu A,Forgues M,Ye QH,et al.Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment[J].Cancer Cell,2006,10(2):99-111.[49]Scheper W,Kelderman S,Fanchi LF,et al.Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers[J].Nat Med,2019,25(1):89-94.[50]Gattinoni L,Zhong XS,Palmer DC,et al.Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells[J].Nat Med,2009,15(7):808-813.[51]Rosenberg SA.Raising the bar:the curative potential of human cancer immunotherapy[J].Sci Transl Med,2012,4(127):127ps8.

相似文献/References:

[1]王利娜,赵雪梅,徐云霞,等.磁共振扩散张量成像在肝细胞癌及 肝转移瘤鉴别诊断价值研究[J].医学信息,2018,31(09):12.[doi:10.3969/j.issn.1006-1959.2018.09.004]
　WANG Li-na,ZHAO Xue-mei,XU Yun-xia,et al.Diagnostic Value of Magnetic Resonance Diffusion Tensor Imaging in Hepatocellular Carcinoma and Liver Metastases[J].Journal of Medical Information,2018,31(09):12.[doi:10.3969/j.issn.1006-1959.2018.09.004]
[2]刘 冰,杨 帅,费锡斌,等.GPC-3联合CK-19免疫组化检测在肝细胞癌诊断及鉴别诊断中的应用[J].医学信息,2019,32(23):169.[doi:10.3969/j.issn.1006-1959.2019.23.054]
　LIU Bing,YANG Shuai,FEI Xi-bin,et al.Application of GPC-3 Combined with CK-19 Immunohistochemical Detection in Diagnosis and Differential Diagnosis of Hepatocellular Carcinoma[J].Journal of Medical Information,2019,32(09):169.[doi:10.3969/j.issn.1006-1959.2019.23.054]
[3]李文华,许传斌,崔景景,等.基于治疗前MR-T2WI影像组学特征预测肝细胞癌射频消融术后早期复发的价值[J].医学信息,2022,35(18):39.[doi:10.3969/j.issn.1006-1959.2022.18.009]
　LI Wen-hua,XU Chuan-bin,CUI Jing-jing,et al.The Value of Predicting Early Recurrence of Hepatocellular Carcinoma After Radiofrequency Ablation Based on Pre-treatment MR-T2WI Radiomics Features[J].Journal of Medical Information,2022,35(09):39.[doi:10.3969/j.issn.1006-1959.2022.18.009]
[4]彭莉蓉,黎村艳,史 杨.肿瘤微环境免疫细胞中差异lncRNA对肝细胞癌预后的预测价值[J].医学信息,2022,35(20):18.[doi:10.3969/j.issn.1006-1959.2022.20.005]
　PENG Li-rong,LI Cun-yan,SHI Yang.The Predictive Value of Differential lncRNA in Tumor Microenvironment Immune Cells for the Prognosis of Hepatocellular Carcinoma[J].Journal of Medical Information,2022,35(09):18.[doi:10.3969/j.issn.1006-1959.2022.20.005]
[5]刘丽丽.CLCVP对肝细胞癌行腹腔镜肝叶切除手术相关指标及肝门阻断时间的影响[J].医学信息,2020,33(19):88.[doi:10.3969/j.issn.1006-1959.2020.19.025]
　LIU Li-li.The Effect of CLCVP on the Operation-related Indexes and Port Occlusion Time in Patients with Hepatocellular Carcinoma Undergoing Laparoscopic Lobectomy[J].Journal of Medical Information,2020,33(09):88.[doi:10.3969/j.issn.1006-1959.2020.19.025]
[6]裴金仙,陈天狮,任巧晶,等.JAK2/STAT3通路在HBV相关肝细胞癌中表达及机制研究[J].医学信息,2022,35(24):59.[doi:10.3969/j.issn.1006-1959.2022.24.012]
　PEI Jin-xian,CHEN Tian-shi,REN Qiao-jing,et al.The Expression and Mechanism of JAK2/STAT3 Pathway in HBV-related Hepatocellular Carcinoma[J].Journal of Medical Information,2022,35(09):59.[doi:10.3969/j.issn.1006-1959.2022.24.012]
[7]杨孟涛,汪 艇,杜 伟,等.miR-181b-5p靶向调控SPP1在肝细胞癌中过表达的临床意义及作用机制[J].医学信息,2022,35(24):79.[doi:10.3969/j.issn.1006-1959.2022.24.016]
　YANG Meng-tao,WANG Ting,DU Wei,et al.Clinical Significance and Mechanism of miR-181b-5p Targeting to Regulate SPP1 Overexpression in Hepatocellular Carcinoma[J].Journal of Medical Information,2022,35(09):79.[doi:10.3969/j.issn.1006-1959.2022.24.016]
[8]孙莹莹,龚先琼.中药单体治疗肝细胞癌的研究[J].医学信息,2021,34(09):33.[doi:10.3969/j.issn.1006-1959.2021.09.008]
　SUN Ying-ying,GONG Xian-qiong.Study on the Treatment of Hepatocellular Carcinoma with Chinese Medicine Monomer[J].Journal of Medical Information,2021,34(09):33.[doi:10.3969/j.issn.1006-1959.2021.09.008]
[9]唐 菀,张晓珣,柴 进.SLCO1B1在肝细胞癌中的表达及其对患者预后的影响[J].医学信息,2023,36(02):12.[doi:10.3969/j.issn.1006-1959.2023.02.002]
　TANG Wan,ZHANG Xiao-xun,CHAI Jin.Expression of SLCO1B1 in Hepatocellular Carcinoma and its Effect on Prognosis[J].Journal of Medical Information,2023,36(09):12.[doi:10.3969/j.issn.1006-1959.2023.02.002]
[10]蒙建源,朱刚健.应用细胞免疫治疗肝细胞癌的研究[J].医学信息,2023,36(05):177.[doi:10.3969/j.issn.1006-1959.2023.05.037]
　MENG Jian-yuan,ZHU Gang-jian.Study on Cellular Immunotherapy for Hepatocellular Carcinoma[J].Journal of Medical Information,2023,36(09):177.[doi:10.3969/j.issn.1006-1959.2023.05.037]

更新日期/Last Update: 1900-01-01