[1]张立洁a,彭 泉b.基于GEO 数据库筛选慢性胰腺炎恶变过程中关键miRNA 和ceRNA 网络构建[J].现代检验医学杂志,2023,38(02):18-24.[doi:10.3969/j.issn.1671-7414.2023.02.004 ]
 ZHANG Li-jiea,PENG Quanb.Screening of Key miRNAs and Construction of Competing Endogenous RNA Network Involved in the Progression from Chronic Pancreatitis to Pancreatic Cancer Based on GEO Database[J].Journal of Modern Laboratory Medicine,2023,38(02):18-24.[doi:10.3969/j.issn.1671-7414.2023.02.004 ]
点击复制

基于GEO 数据库筛选慢性胰腺炎恶变过程中关键miRNA 和ceRNA 网络构建()
分享到:

《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年02期
页码:
18-24
栏目:
论著
出版日期:
2023-03-15

文章信息/Info

Title:
Screening of Key miRNAs and Construction of Competing Endogenous RNA Network Involved in the Progression from Chronic Pancreatitis to Pancreatic Cancer Based on GEO Database
文章编号:
1671-7414(2023)02-018-07
作者:
张立洁a彭 泉b
(解放军第 901医院 a.肿瘤中心;b.普外科,合肥 230031)
Author(s):
ZHANG Li-jiea PENG Quanb
(a.Tumor Diagnosis and Treatment Center;b. Department of General Surgery, 901th Hospital of PLA, Hefei 230031,China)
关键词:
胰腺癌慢性胰腺炎微小 RNA竞争性内源 RNA
分类号:
R735.9; R730.43
DOI:
10.3969/j.issn.1671-7414.2023.02.004
文献标志码:
A
摘要:
目的 筛选慢性胰腺炎(chronic pancreatitis, CP)进展到胰腺癌(pancreatic cancer, PC)过程中发挥潜在作用的 miRNA及其调控网络。方法 从 GEO数据库中下载芯片数据 GSE24279和 GSE25820,筛选出在 CP和 PC中差异表达的 miRNA(differential expression miRNA,DEM)。预测 DEM的靶基因和长链非编码 RNA(long non-coding RNA),随后进行靶基因富集分析,构建蛋白互作网络(protein-protein interaction, PPI)并筛选出枢纽基因和具有特殊生物学功能的模块,通过综合分析 DEM,枢纽基因和 LncRNA的表达和预后,基于竞争性内源 RNA(competing endogenous RNAs, ceRNA)的理论,构建 miRNA的调控网络。结果 筛选出 16个 DEM,其靶基因参与共生过程,细胞器组织的正调控,细胞质的核周区域和双链 RNA结合。从 PPI网络中,筛选出 17个枢纽基因和 3个模块。综合分析后,将 hsa-miR-221-3p,hsa-miR-222-3p,hsa-miR-210-3p及 RNPS1,MGRN1作为 CP进展为 PC中关键节点。 41个 LncRNA结合关键 DEM,其中 MIAT,DANT2,TTN-AS1,PAXIP1-AS2和 LINC00473具有预后价值。综合以上结果,构建出包含 3个 DEM,2个基因和 5个 LncRNA的 ceRNA调控网络。结论 研究采用的整合分析方法有助于揭示 CP恶变的机制,构建的 LncRNA-miRNA-基因调控网络,为预测和治疗由 CP进展为 PC的患者提供了新的生物学靶点。
Abstract:
Objective To find the key miRNAs and their potential molecular mechanisms in the progression from chronic pancreatitis (CP) to pancreatic cancer (PC). Methods Microarray data GSE24279 and GSE25820 were downloaded from Gene Expression Omnibus (GEO) database, and screened out the differential expressed miRNAs (DEM) in CP and PC. Predicted the target gene and LncRNAs (long non-coding RNA) of DNA, and then carried out the enrichment analysis of target genes, constructed the Protein-protein interaction (PPI) and screened out the hinge genes and modules with special and prognosis of DEM, hinge genes and LncRNA, built the miRNA regulatory network based on the theory of competitive endogenous RNAs(ceRNA).Results 16 DEM were found both in GSE24279 and GSE25820, enrichment analyses showed that targets of overlapped DEM were significantly enriched in symbiont process, positive regulation of organelle organization, perinuclear region of cytoplasm and double-stranded RNA binding. From the PPI network, 17 nodes and 3 modules were selected. According to the expression and prognostic, 3 upregulated DEM (hsa-miR-221-3p, hsa-miR-222-3p, hsa-miR-210-3p) and 2 target genes (RNPS1 and MGRN1) were screened, subsequently, 41 LncRNAs were explored to potentiality bind to those 3 key DEM, 5 of them (MIAT, DANT2, TTN-AS1, PAXIP1-AS2 and LINC00473) had the positive prognostic value. finally, constructed a regulatory network based on competing endogenous RNA (ceRNA) hypothesis. Conclusion The methodology in this study contributed to understanding the pathogenesis involved in the progression from CP to PC, the novel LncRNA-miRNA-gene regulatory network can provide new clues to predict the development of PC in CP patients.

参考文献/References:

[1] 郭勇 , 龚建平 , 李培志.胰腺癌的综合治疗进展 [J].国际外科学杂志 , 2021, 48(9): 638-643. GUO Yong, GONG Jianping, LI Peizhi. Advances in the comprehensive treatment of pancreatic cancer[J]. International Journal of Surgery, 2021, 48(9): 638-643.
[2] LOWENFELS A B, MAISONNEUVE P, CAVALLINI G, et al. Pancreatitis and the risk of pancreatic cancer [J]. N Engl J Med, 1993, 328(20):1433-1437.
[3] 李超 , 朱晓丹 , 张玲华 , 等 .基于 GEO数据库整合 miRNA-mRNA表达谱筛选卵巢癌的关键基因分子及生物信息分析 [J].现代检验医学杂志 , 2021, 36(5): 38-42. LI Chao, ZHU Xiaodan, ZHANG Linghua, et al. Screening key biomarkers and bioinformatic analysis of ovarian cancer by integrated miRNA-mRNA expression profiles based on GEO database[J]. Journal of Modern Laboratory Medicine, 2021, 36(5): 38-42.
[4] 吴良银 , 李文丽 , 刘俊.基于 GEO数据的病毒相关性肝癌潜在生物基因标志物的筛选及生物信息学分析 [J].现代检验医学杂志 , 2021, 36(6): 106-110. WU Liangyin, LI Wenli, LIU Jun. Screening and bioinformatics analysis of potential biomarkers for virus-associated hepatocellular carcinoma based on GEO data[J]. Journal of Modern Laboratory Medicine, 2021, 36(6): 106-110.
[5] XIE J, WEN J T, XUE X J, et al. MiR-221 inhibits proliferation of pancreatic cancer cells via down regulation of SOCS3[J]. European Review for Medical and Pharmacological Sciences, 2018, 22(7): 1914-1921.
[6] 高杰 , 张晓 , 魏超 .差异表达 miRNA在胰腺癌预后判断中的价值 [J].癌变·畸变·突变 , 2019, 31(3): 173-179. GAO Jie, ZHANG Xiao, WEI Chao. Involvement of differentially expressed miRNA in prognosis of pancreatic cancers[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(3): 173-179.
[7] 胡应霞 , 张海蓉 , 石围 , 等.血浆 miR-155, miR-196a, miR-21和 miR-210对胰腺癌的早期诊断价值 [J]. 肿瘤 , 2015, 35(10): 1135-1143. HU Yingxia, ZHANG Hairong, SHI Wei, et al. Early diagnostic value of plasma miR-155, miR-196a, miR-21 and miR-210 in patients with pancreatic cancer[J]. Tumor, 2015, 35(10): 1135-1143.
[8] XIN Lei, GAO Jun, WANG Dan, et al. Novel blood-based microRNA biomarker panel for early diagnosis of chronic pancreatitis[J]. Scientific Reports, 2017, 7: 40019.
[9] ZHANG Yuqing, LI Min, WANG Hao, et al. Profiling of 95 microRNAs in pancreatic cancer cell lines and surgical specimens by real-time PCR analysis[J]. World Journal of Surgery, 2009, 33(4): 698-709.
[10] WANG Lei, ZHENG Jianming, SUN Chang, et al. MicroRNA expression levels as diagnostic biomarkers for intraductal papillary mucinous neoplasm[J]. Oncotarget, 2017, 8(35): 58765-58770.
[11] 孙莹莹 , 陆颖影 , 靖大道.慢性胰腺炎和胰腺癌发生及发展中肠道微生态的研究进展 [J].国际消化病杂志 , 2021, 41(4): 240-243. SUN Yingying, LU Yingying, JING Dadao. Research progress of intestinal microbiology in the development of chronic pancreatitis and pancreatic cancer [J]. International Journal of Digestive Diseases, 2021, 41(4): 240-243.
[12] WANG Hao, JIANG Yanfeng, LU Ming, et al. STX12 LncRNA/miR-148a/SMAD5 participate in the regulation of pancreatic stellate cell activation through a mechanism involving competing endogenous RNA[J]. Pancreatology, 2017, 17(2): 237-246.
[13] QI Z, ZHANG B, ZHANG J, et al. MicroRNA-30b inhibits non-small cell lung cancer cell growth by targeting the epidermal growth factor receptor[J]. Neoplasma, 2018, 65(2): 192-200.
[14] WANG Ning, XIANG Xiaohui, CHEN Kai, et al. Targeting of NT5E by miR-30b and miR-340 attenuates proliferation, invasion and migration of gallbladder carcinoma[J]. Biochimie, 2018, 146: 56-67.
[15] LIU Wenjuan, LI Honghong, WANG Yan, et al. MiR-30b-5p functions as a tumor suppressor in cell proliferation, metastasis and epithelial-to-mesenchymal transition by targeting G-protein subunit α-13 in renal cell carcinoma[J]. Gene, 2017, 626: 275-281.
[16] XIONG Yicheng, WANG Yao, WANG Lei, et al. MicroRNA-30b targets Snail to impede epithelial-mesenchymal transition in pancreatic cancer stem cells[J]. Journal of Cancer, 2018, 9(12): 2147-2159.
[17] WHITE E, MEHNERT J M, AUTOPHAGY C C. Metabolism and cancer[J]. Clin Cancer Res, 2015, 21(22): 5037-5046.
[18] MAERTIN S, ELPERIN J M, LOTSHAW E, et al. Roles of autophagy and metabolism in pancreatic cancer cell adaptation to environmental challenges[J]. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2017, 313(5): G524-G536.
[19] ENDO S, NAKATA K, OHUCHIDA K, et al. Autophagy is required for activation of pancreatic stellate cells, associated with pancreatic cancer progression and promotes growth of pancreatic tumors in mice[J]. Gastroenterology, 2017, 152(6): 1492-1506, e24.
[20] KWON J J, WILLY J A, QUIRIN K A, et al. Novel role of miR-29a in pancreatic cancer autophagy and its therapeutic potential[J]. Oncotarget, 2016, 7(44): 71635-71650.
[21] HU Chunling, HART S N, POLLEY E C, et al. Association between inherited germline mutations in cancer predisposition genes and risk of pancreatic cancer[J]. JAMA , 2018, 319(23): 2401-2409.
[22] 臧龙军 , 陈东杰 , 高文哲 , 等 .长链非编码 RNA SOX21-AS1调控 miR-31-5p/MMP-16轴对胰腺癌细胞活性与增殖的影响 [J].中国普通外科杂志 , 2022, 31(3): 329-339. ZANG Longjun, CHEN Dongjie, GAO Wenzhe, et al. Effect of long non-coding RNA SOX21-AS1 on viability and proliferation of pancreatic cancer cells via modulating miR-31-5p/MMP-16 axis[J]. Chinese Journal of General Surgery, 2022, 31(3): 329-339.
[23] 王东琴 , 霍浩然 , 秦瑞峰 , 等 .胰腺癌患者血清 LncRNA-SNHG11的表达水平及其临床意义 [J].现代检验医学杂志 , 2022, 37(1): 125-129, 144. WANG Dongqin, HUO Haoran, QIN Ruifeng, et al. Expression level of serum LncRNA-SNHG11 in patients with pancreatic cancer and its clinical significance[J]. Journal of Modern Laboratory Medicine, 2022, 37(1): 125-129, 144.
[24] LIU Hao, YU Kaihuan, MA Peng, et al. Long noncoding RNA myocardial infarction-associated transcript regulated the pancreatic stellate cell activation to promote the fibrosis process of chronic pancreatitis[J]. Journal of Cellular Biochemistry, 2019, 120(6): 9547-9555.
[25] ZHOU Wenyang, ZHANG Mingming, LIU Chang, et al. Long noncoding RNA LINC00473 drives the progression of pancreatic cancer via upregulating programmed death-ligand 1 by sponging microRNA-195-5p[J]. Journal of Cellular Physiology, 2019, 234(12): 23176-23189.

相似文献/References:

[1]党珊a,周健a,杨帆b,等.胰腺癌组织中缺氧诱导因子-2α的表达及临床意义[J].现代检验医学杂志,2015,30(06):32.[doi:10.3969/j.issn.1671-7414.2015.06.009]
 DANG Shana,ZHOU Jiana,YANG Fanb,et al.Expression of Hypoxia Inducible Factor 2α in Pancreatic Carcinoma and Its Clinical Significance[J].Journal of Modern Laboratory Medicine,2015,30(02):32.[doi:10.3969/j.issn.1671-7414.2015.06.009]
[2]韦 莉,缪淑贤,王 敏,等.胰腺癌患者血清尿酸、肌酐水平检测及尿酸/肌酐比值的临床意义[J].现代检验医学杂志,2019,34(04):99.[doi:10.3969/j.issn.1671-7414.2019.04.024]
 WEI Li,MIAO Shu-xian,WANG Min,et al.Clinical Significance of Serum Uric Acid,Creatinine and Uric Acid/Creatinine Ratio in Pancreatic Ductal Adenocarcinoma[J].Journal of Modern Laboratory Medicine,2019,34(02):99.[doi:10.3969/j.issn.1671-7414.2019.04.024]
[3]邢瑞青,彭道荣,刘 杨.血清CA199,KL-6和PIVKA-Ⅱ水平联合检测在胰腺癌诊断中的应用价值分析[J].现代检验医学杂志,2021,36(05):100.[doi:10.3969/j.issn.1671-7414.2021.05.022]
 XING Rui-qing,PENG Dao-rong,LIU Yang.Application Value of Combined Detection of Serum CA199,KL-6 andPIVKA -Ⅱ Levels in the Diagnosis of Patients with Pancreatic Cancer[J].Journal of Modern Laboratory Medicine,2021,36(02):100.[doi:10.3969/j.issn.1671-7414.2021.05.022]
[4]王东琴,霍浩然,秦瑞峰,等.胰腺癌患者血清 lncRNA-SNHG11的表达水平及其临床意义[J].现代检验医学杂志,2022,37(01):125.[doi:10.3969/j.issn.1671-7414.2022.01.025]
 WANG Dong-qin,HUO Hao-ran,QIN Rui-feng,et al.Expression Level of Serum lncRNA-SNHG11 in Patients with Pancreatic Cancer and Its Clinical Significance[J].Journal of Modern Laboratory Medicine,2022,37(02):125.[doi:10.3969/j.issn.1671-7414.2022.01.025]
[5]王军堂a,齐普良a,张金刚a,等.hsa_circ_0006950 调控miR-124-3p/EZH2 轴促进胰腺癌细胞增殖与迁移的机制研究[J].现代检验医学杂志,2022,37(05):93.[doi:10.3969/j.issn.1671-7414.2022.05.019]
 WANG Jun-tanga,QI Pu-lianga,ZHANG Jin-ganga,et al.Mechanism of hsa_circ_0006950 Regulating miR-124-3p /EZH2 Axis to Promote the Proliferation and Migration of Pancreatic Cancer Cells[J].Journal of Modern Laboratory Medicine,2022,37(02):93.[doi:10.3969/j.issn.1671-7414.2022.05.019]
[6]张莉娜,张霁雯,罗 酩,等.胰腺癌组织CTTN 和miR-545-3p 表达水平及其与临床病理和预后的相关性研究[J].现代检验医学杂志,2022,37(06):99.[doi:10.3969/j.issn.1671-7414.2022.06.018]
 ZHANG Li-na,ZHANG Ji-wen,LUO Ming,et al.Expression Levels of CTTN and miR-545-3p in Pancreatic Cancer Tissues and Their Correlation with Clinicopathology and Prognosis[J].Journal of Modern Laboratory Medicine,2022,37(02):99.[doi:10.3969/j.issn.1671-7414.2022.06.018]
[7]檀占海,陈建荣,张吉发,等.胰腺癌组织中METTL14 和GFPT1 的水平表达与临床预后价值研究[J].现代检验医学杂志,2023,38(05):99.[doi:10.3969/j.issn.1671-7414.2023.05.019]
 TAN Zhanhai,CHEN Jianrong,ZHANG Jifa,et al.Expression of METTL14 and GFPT1 in Pancreatic Cancer and Their Clinical Prognostic Value[J].Journal of Modern Laboratory Medicine,2023,38(02):99.[doi:10.3969/j.issn.1671-7414.2023.05.019]
[8]夏菊芳,刘 洪.胰腺癌组织中KYNU mRNA 的表达及其与免疫浸润和预后的相关性研究[J].现代检验医学杂志,2024,39(02):57.[doi:10.3969/j.issn.1671-7414.2024.02.011]
 XIA Jufang,LIU Hong.Expression of KYNU mRNA in Pancreatic Cancer Tissue and Its Correlation with Immune Infiltration and Prognosis[J].Journal of Modern Laboratory Medicine,2024,39(02):57.[doi:10.3969/j.issn.1671-7414.2024.02.011]

备注/Memo

备注/Memo:
收稿日期:2022-11-14修回日期:2022-12-12
基金项目:中国人民解放军联勤保障部队第 901医院院管课题(NO.2021YGYB06):ADAM8基因在胰腺癌中的表达及其启动子区甲基化状态相关性研究。
作者简介:张立洁(1983-),女,医学硕士,副主任医师,研究方向:肿瘤的分子诊断及靶向治疗, E-mail:zhanglijie0506@163.com。
通讯作者:彭泉,男,副主任医师,研究方向:肿瘤表观遗传学及生物信息学分析,E-mail:pengquan1983@163.com。

更新日期/Last Update: 2023-03-15