|Table of Contents|

Analysis of anoikis-related miRNA spredicting prognosis in hepatocellular carcinoma

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 04
Page:
601-609
Research Field:
Publishing date:

Info

Title:
Analysis of anoikis-related miRNA spredicting prognosis in hepatocellular carcinoma
Author(s):
LIN Yingxue1CUI Haipeng2YAO Yinhui1MENG Xin1WANG Ying1
1.Department of Pharmacy,Affiliated Hospital of Chengde Medical University,Hebei Chengde 067000,China;2.Department of Pathophysiology,Chengde Medical University,Hebei Chengde 067000,China.
Keywords:
HCCanoikismiRNAsprognosis
PACS:
R735.7
DOI:
10.3969/j.issn.1672-4992.2024.04.003
Abstract:
Objective:Use The Cancer Genome Atlas (TCGA) database to screen anoikis-related miRNAs (armiRNAs) in hepatocellular carcinoma (HCC) tissues and construct a prognostic model based on the selected miRNAs.To explored the relevance of armiRNAs and the prognosis of HCC,hope to provide new targets for liver cancer therapy.Methods:RNA transcription data were downloaded from the TCGA.The differentially expressed armiRNAs were screened in HCC and paraneoplastic tissues.Univariate Cox regression and LASSO regression analyses were used to identify prognostically significant armiRNAs.The reliability was assessed by ROC curves,then a prognostic nomogram model was constructed.Using this model,gene enrichment analysis and drug susceptibility studies were performed using the Kyoto Gene and Genome Encyclopedia (KEGG).Validation of differentially expressed armiRNAs in human normal hepatocyte cell line LO2 and three human hepatocellular carcinoma cell lines by RT-qPCR.Results:This study screened seven armiRNAs,then classified the liver cancer samples into high-risk and low-risk groups according to risk scores.Kaplan-Meier survival curves showed significant differences between the two groups.Mortality increased with risk scores.The AUC of the ROC curves predicting 1-,2- and 3-year survival were 0.794,0.789,and 0.781,indicating a higher degree of discrimination in the model.High-risk groups had higher susceptibility to multiple anti-tumour drugs.Compared with LO2 cells,the expression of hsa-miR-4661,hsa-miR-1180 was significantly increased in three kinds of human HCC cell lines,the expression of hsa-miR-139,hsa-miR-101-2,hsa-miR-326,and hsa-miR-29c was significantly decreased,whereas hsa-miR-509-3-5p was significantly reduced in HepG2 cells and significantly increased in SMMC-7721 and MHCC97 cells.Conclusion:This study identified seven armiRNAs.Models which based on these genes are good predictors of survival and drug sensitivity in patients with HCC.These results may provide some guidance for the exploration of prognostic markers and clinical individualized treatment of HCC.

References:

[1] 梁增辉.MiR-183在肝癌中的表达水平及其临床意义[D].天津:天津医科大学,2014. LIANG ZH.Expression and significance of microRNA-183 in hepatocellular carcinoma [D].Tianjin:Tianjin Medical University,2014.
[2] ZHANG YY,LI XW,LI XD.Comprehensive analysis of anoikis-related long non-coding RNA immune infiltration in patients with bladder cancer and immunotherapy[J].Frontiers in Immunology,2022,25:01-12.
[3]ZHANG HF,HUGHES CS,LI W,et al.Proteomic screens for suppressors of Anoikis identify IL1RAP as a promising surface target in Ewing sarcoma[J].Cancer Discovery,2021,11(11):2884-2903.
[4] DU S,MIAO J,ZHU Z,et al.NADPH oxidase 4 regulates anoikis resistance of gastric cancer cells through the generation of reactive oxygen species and the induction of EGFR[J].Cell Death Dis,2018,9(10):948.
[5] HU X,ZHAO Y,WEI L,et al.CCDC178 promotes hepatocellular carcinoma metastasis through modulation of anoikis[J].Oncogene,2017,36(28):4047-4059.
[6] SONG J,LIU Y,LIU F,et al.The 14-3-3σ protein promotes HCC anoikis resistance by inhibiting EGFR degradation and thereby activating the EGFR-dependent ERK1/2 signaling pathway[J].Theranostics,2021,11(3):996-1015.
[7] MEN JR,TAN JJ,SUN HL.The identification and analysis of a miRNA risk score model for hepatocellular carcinoma prognosis[J].Progress in Biochemistry and Biophysics,2020,47(4):344-360.
[8] CHEN X,ZHANG Q,MA W,et al.The abnormal expression of microRNA-542-3p in hepatocellular carcinoma and its clinical significance[J].Dis Markers,2018,2018:1-9.
[9] SHAO P,SUN D,WANG L,et al.Deep sequencing and comprehensive expression analysis identifies several molecules potentially related to human poorly differentiated hepatocellular carcinoma[J].FEBS Open Bio,2017,7(11):1696-1706.
[10] SAUERBREI W,ROYSTON P,BINDER H.Selection of important variables and determination of functional form for continuous predictors in multivariable model building[J].Stat Med,2007,26(30):5512-5528.
[11] HONG W,LIANG L,GU Y,et al.Immune-related lncrna to construct novel signature and predict the immune landscape of human hepatocellular carcinoma[J].Mol Ther Nucleic Acids,2020,(22):937-947.
[12] WANG Y,YAO Y,ZHAO J,et al.Development of an autophagy-related gene prognostic model and nomogram for estimating renal clear cell carcinoma survival[J].J Oncol,2021,2021:8810849.
[13] 李忠,吴二斌,邹善贵,等.基于生物信息学方法构建肝癌患者预后相关内源竞争RNA调控网络[J].黑龙江医学,2023,47(05):521-526. LI Z,WU EB,ZOU SG,et al.Bioinformatics-based approach for the construction of prognosis-related competing endogenous RNA regulatory network in patients with hepatocellular carcinoma[J].Heilongjiang Medical Journal,2023,47(05):521-526.
[14] HUANG FY,WONG KH,TSUI WM,et al.Targeted genomic profiling identifies frequent deleterious mutations in FAT4,and TP53,genes in HBV-associated hepatocellular carcinoma[J].BMC Cancer,2019,19(1):789-799.
[15] VILCHEZ V.Targeting Wnt/β -catenin pathway in hepatocellular carcinoma treatment[J].World J Gastroenterol,2016,22(2):823-832.
[16]GEDALY R,ANGULO P,HUNDLEY J,et al.PKI-587 and sorafenib targeting PI3K/AKT/mTOR and Ras/Raf/MAPK pathways synergistically inhibit HCC cell proliferation[J].J Surg Res,2012,176(2):542-548.
[17]郑骞,周亮,徐建庆,等.miR-26b通过调节Notch1信号通路参与原发性肝细胞肝癌侵袭的机制研究[J].现代肿瘤医学, 2020,28(14):2390-2395. ZHENG Q,ZHOU L,XU JQ,et al.miR-26b is involved in cell invasion in hepatocellular carcinoma by regulating the Notch1 signal pathway[J].Modern Oncology,2020,28(14):2390-2395.
[18] ZHANG L,YANG P,WANG J,et al.MiR-22 regulated T cell differentiation and hepatocellular carcinoma growth by directly targeting Jarid2[J].Am J Cancer Res,2021,11(5):2159-2173.
[19] ZHU HR,YU XN,ZHANG GC,et al.Comprehensive analysis of long non-coding RNA-messenger RNA-microRNA co-expression network identifies cell cycle-related lncRNA in hepatocellular carcinoma[J].Int J Mol Med,2019,44(5):1844-1854.
[20]DIAO X,GUO C,LI S.Identification of a novel anoikis-related gene signature to predict prognosis and tumor microenvironment in lung adenocarcinoma[J].Thorac Cancer,2023,14(3):320-330.
[21]王华,吴维光,王筝,等.微小RNA-125b过表达对卵巢癌SKOV3细胞抗失巢凋亡的作用[J].中国妇产科临床杂志,2014,15(5):391-394. WANG H,WU WG,WANG Z,et al.Overexpression of microRNA-125b on anoikis resistance in human ovarian cancer celll ine SKOV3[J].Chinese Journal of Clinical Obstetrics and Gynecology,2014,15(5):391-394.
[22] ZHANGN Y,LI T,GUO PB,et al.MiR-424-5p reversed epithelial-mesenchymal transition of anchorage-independent HCC cells by directly targeting ICAT and suppressed HCC progression[J].Sci Rep,2014,4:6248.
[23] 汪佳兵,王石健,魏静,等.微小RNA-520e通过下调自噬调控肝癌细胞失巢凋亡抵抗[J].江苏医药,2022,48(11):1081-1089. WANG JB,WANG SJ,WEI J,et al.MicroRNA-520e regulating anoikis resistance of hepatocellular carcinoma cells by downregulating autophagy [J].Jiangsu Medical Journal,2022,48(11):1081-1089.
[24] HUA S,LEI L,DENG L,et al.miR-139-5p inhibits aerobic glycolysis,cell proliferation,migration,and invasion in hepatocellular carcinoma via a reciprocal regulatory interaction with ETS1[J].Oncogene,2018,37(12):1624-1636.
[25] LI T,YIN J,YUAN L,et al.Downregulation of microRNA-139 is associated with hepatocellular carcinoma risk and short-term survival[J].Oncol Rep,2014,31(4):1699-1706.
[26] 孔令玉,朱天怡.微小RNA-1180在非小细胞肺癌中的表达及其临床意义[J].实用临床医药杂志,2022,26(3):76-80. KONG LY,ZHU TY.Expression of miR-1180 in non-small cell lung cancer and its clinical significance[J].Journal of Clinical Medicine in Practice,2022,26(3):76-80.
[27] ZHOU X,ZHU H,MA C,et al.MiR-1180 promoted the proliferation of hepatocellular carcinoma cells by repressing TNIP2 expression [J].Biomed Pharmacother,2016,79:315-320.
[28] 黄成军,关菁,覃丽华.微小RNA-1180对肝癌细胞侵袭迁移和TGF-β信号通路的影响[J].临床肿瘤学杂志,2019,24(11):989-993. HUANG CJ,GUAN J,QIN LH.Effect of microRNA-1180 on invasion,migration and TGF-β signaling pathway of hepatoma cells[J].Chinese Clinical Oncology,2019,24(11):989-993.
[29] WANG H,CHEN W,QI Y,et al.miR-29c suppresses the malignant phenotype of hepatocellular carcinoma cells in vitro by mediating TPX2 associated with immune infltration [J].Dig Dis Sci,2023,68(5):1923-1935.
[30] HYO JC,GEUM OB,CHUL WS,et al.Exosomal microRNA-4661-5p-based serum panel as a potential diagnostic biomarker for early-stage hepatocellular carcinoma[J].Cancer Med,2020,9(15):5459-5472.
[31]MO Y,HE L,LAI Z,et al.Gold nano-particles (AuNPs) carrying miR-326 targets PDK1/AKT/c-myc axis in hepatocellular carcinoma[J].Artif Cells Nanomed Biotechnol,2019,47(1):2830-2837.
[32] WANG Y,YANG F,PENG Q,et al.Long non-coding RNA SNHG1 activates glycolysis to promote hepatocellular cancer progression through the miR-326/PKM2 axis[J].J Gene Med,2022,24(8):e3440.
[33] LI Z,QU Z,WANG Y,et al.miR-101-3p sensitizes non-small cell lung cancer cells to irradiation[J].Open Medicine,2020,15(1):413-423.
[34]LI K.MiR-509-3-5p inhibits colon cancer malignancy by suppressing GTSE1[J].Biochem Biophys Res Commun,2021,570:175-183.
[35] ZHANG J,ZHU Z,SHENG J,et al.miR-509-3-5P inhibits the invasion and lymphatic metastasis by targeting PODXL and serves as a novel prognostic indicator for gastric cancer[J].Oncotarget,2017,8(21):34867-34883.

Memo

Memo:
河北省医学科学研究课题计划(编号:20200183);河北省高等学校科学研究青年基金(编号:QN2023017);河北省中医药类科研计划项目(编号:2022152)
Last Update: 1900-01-01