|Table of Contents|

The expression of long non-coding RNA NRAV in HCC tissues and cells and its effect on cancer cell glycolysis

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

Issue:
2023 22
Page:
4141-4146
Research Field:
Publishing date:

Info

Title:
The expression of long non-coding RNA NRAV in HCC tissues and cells and its effect on cancer cell glycolysis
Author(s):
WANG Tianyuan1; JIANG Wei2; XIAO Xuelian3; GUO Cheng3; TU Kangsheng3
1.Department of Clinical Laboratory,Huazhong University of Science and Technology Union Shenzhen Hospital,Guangdong Shenzhen 518000,China;2.School of Nursing,Shaoyang University,Hunan Shaoyang 422000,China;3.Department of Hepatobiliary Surgery,the First Affiliated Hospital of Xi'an Jiaotong University,Shaanxi Xi'an 710061,China.
Keywords:
hepatocellular carcinoma; negative regulator of antiviral response (NRAV); glycolysis; therapeutic target
PACS:
R735.7
DOI:
10.3969/j.issn.1672-4992.2023.22.008
Abstract:
Objective:To explore the expression of long non-coding RNA negative regulator of antiviral response(NRAV) in hepatocellular carcinoma (HCC) tissues and cells and its effect on glycolysis and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) expression in HCC cells.Methods:RT-qPCR was carried out to detect NRAV and PFKFB3 mRNA expression.The expression of NRAV was downregulated or upregulated by transfecting shRNA or overexpression plasmid in HCC cells.The glycolysis of HCC cells was evaluated by detecting glucose uptake,lactate production and ATP levels.The expression of PFKFB3 protein level was detected by Western blotting.Results:NRAV expression in HCC tissues was significantly higher than that in tumor-adjacent tissues.The levels of NRAV in HCC cell lines (Hep3B,PLC/PRF/5,HCCLM3,SK-Hep-1 and Huh7) were significantly higher than that normal hepatic cell line (MIHA).NRAV knockdown significantly reduced the glucose uptake,lactate production,and ATP levels of HCC cells.While NRAV overexpression markedly enhanced the glycolysis of HCC cells.NRAV was significantly positively correlated with PFKFB3 mRNA expression in HCC tissues.The knockdown of NRAV significantly decreased the expression of PFKFB3 in HCC cells,while NRAV overexpression prominently increased PFKFB3 expression.Conclusion:NRAV expression is up-regulated in HCC tissues and cell lines.NRAV promotes the glycolysis of HCC cells and enhances PFKFB3 expression,suggesting that NRAV is a potential new target for anti-HCC therapy.

References:

［1］LEE YT,WANG JJ,LUU M,et al.The mortality and overall survival trends of primary liver cancer in the United States［J］.J Natl Cancer Inst,2021,113(11):1531-1541.
［2］TOH TB,LIM JJ,CHOW EK.Epigenetics of hepatocellular carcinoma［J］.Clin Transl Med,2019,8(1):13.
［3］LOFTFIELD E,STEPIEN M,VIALLON V,et al.Novel biomarkers of habitual alcohol intake and associations with risk of pancreatic and liver cancers and liver disease mortality［J］.J Natl Cancer Inst,2021,113(11):1542-1550.
［4］EI-KHOUEIRY AB,HANNA DL,LLOVET J,et al.Cabozantinib:An evolving therapy for hepatocellular carcinoma［J］.Cancer Treat Rev,2021,98:102221.
［5］王东,陈玉晓,董转丽,等.中晚期肝癌免疫治疗现状与前景［J］.现代肿瘤医学,2022,30(11):2065-2068. WANG D,CHEN YX,DONG ZL,et al.The present situation and prospect of immunotherapy for advanced hepatocellular carcinoma［J］.Modern Oncology,2022,30(11):2065-2068.
［6］YANG Z,JIANG S,SHANG J,et al.LncRNA:Shedding light on mechanisms and opportunities in fibrosis and aging［J］.Ageing Res Rev,2019,52:17-31.
［7］包晗,苏洪英.长链非编码RNA作为肝癌血清肿瘤标志物的研究进展［J］.现代肿瘤医学,2021,29(13):2355-2358. BAO H,SU HY.Research progress of lncRNA acting as novel sera biomarkers for hepatocellular carcinoma［J］.Modern Oncology,2021,29(13):2355-2358.
［8］LIM LJ,WONG SYS,HUANG F,et al.Roles and regulation of long noncoding RNAs in hepatocellular carcinoma［J］.Cancer Res,2019,79(20):5131-5139.
［9］OUYANG J,ZHU X,CHEN Y,et al.NRAV,a long noncoding RNA,modulates antiviral responses through suppression of interferon-stimulated gene transcription［J］.Cell Host Microbe,2014,16(5):616-626.
［10］XU Q,WANG Y,HUANG W.Identification of immune-related lncRNA signature for predicting immune checkpoint blockade and prognosis in hepatocellular carcinoma［J］.Int Immunopharmacol,2021,92:107333.
［11］SONG D,WANG X,WANG Y,et al.Integrated analysis of N1-methyladenosine methylation regulators-related lncRNAs in hepatocellular carcinoma［J］.Cancers(Basel),2023,15(6):1800.
［12］DAI T,LI J,YE L,et al.Prognostic role and potential mechanisms of N6-methyladenosine-related long noncoding RNAs in hepatocellular carcinoma［J］.J Clin Transl Hepatol,2022,10(2):308-320.
［13］ANASTASIADOU E,JACOB LS,SLACK FJ.Non-coding RNA networks in cancer［J］.Nat Rev Cancer,2018,18(1):5-18.
［14］SLACK FJ,CHINNAIYAN AM.The role of non-coding RNAs in oncology［J］.Cell,2019,179(5):1033-1055.
［15］WANG L,SUN L,LIU R,et al.Long non-coding RNA MAPKAPK5-AS1/PLAGL2/HIF-1alpha signaling loop promotes hepatocellular carcinoma progression［J］.J Exp Clin Cancer Res,2021,40(1):72.
［16］CHEN T,LIR R,NIU Y,et al.HIF-1alpha-activated long non-coding RNA KDM4A-AS1 promotes hepatocellular carcinoma progression via the miR-411-5p/KPNA2/AKT pathway［J］.Cell Death Dis,2021,12(12):1152.
［17］谢利华,周琳.lncRNA MEG3在肿瘤发生发展中的功能作用与机制研究进展［J］.现代肿瘤医学,2022,30(11):2086-2090. XIE LH,ZHOU L.Research progress on the function and mechanism of lncRNA MEG3 in tumorigenesis and development［J］.Modern Oncology,2022,30(11):2086-2090.
［18］MAIMAITI A,JIANG L,WANG X,et al.Identification and validation of an individualized prognostic signature of lower-grade glioma based on nine immune related long non-coding RNA［J］.Clin Neurol Neurosurg,2021,201:106464.
［19］WANG Z,LIU Y,ZHANG J,et al.An immune-related long noncoding RNA signature as a prognostic biomarker for human endometrial cancer［J］.J Oncol,2021,2021:9972454.
［20］WANG HQ,QIAN CH,GUO ZY,et al.Long noncoding RNA negative regulator of antiviral response contributes to pancreatic ductal adenocarcinoma progression via targeting miR-299-3p［J］.World J Gastroenterol,2022,28(35):5141-5153.
［21］NICKNAM A,KHOJASTEH POUR S,HASHEMNEJAD MA,et al.Expression analysis of Rho GTPase-related lncRNAs in breast cancer［J］.Pathol Res Pract,2023,244:154429.
［22］FENG Y,HU X,MA K,et al.Genome-wide screening identifies prognostic long noncoding RNAs in hepatocellular carcinoma［J］.Biomed Res Int,2021,2021:6640652.
［23］CHEN ZA,TIAN H,YAO DM,et al.Identification of a ferroptosis-related signature model including mRNAs and lncRNAs for predicting prognosis and immune activity in hepatocellular carcinoma［J］.Front Oncol,2021,11:738477.
［24］WU ZH,LI ZW,YANG DL,et al.Development and validation of a pyroptosis-related long non-coding RNA signature for hepatocellular carcinoma［J］.Front Cell Dev Biol,2021,9:713925.
［25］YIN L,ZHOU L,GAO S,et al.Classification of hepatocellular carcinoma based on N6-methylandenosine-related lncRNAs profiling［J］.Front Mol Biosci,2022,9:807418.
［26］WANG T,YANG Y,SUN T,et al.The pyroptosis-related long noncoding RNA signature predicts prognosis and indicates immunotherapeutic efficiency in hepatocellular carcinoma［J］.Front Cell Dev Biol,2022,10:779269.
［27］CHEN X,SUN M,FENG W,et al.An integrative analysis revealing cuproptosis-related lncRNAs signature as a novel prognostic biomarker in hepatocellular carcinoma［J］.Front Genet,2023,14:1056000.
［28］CHEN M,WU GB,HUA S,et al.Identification and validation of a prognostic model of necroptosis-related lncRNAs in hepatocellular carcinoma［J］.Front Genet,2022,13:907859.
［29］WANG Q,TANG Y,GE Y,et al.Long non-coding RNA NRAV enhances proliferation and invasion of hepatocellular carcinoma cells by modulating the Wnt/beta-catenin signaling pathway［J］.Bioengineered,2022,13(4):10026-10037.
［30］HANAHAN D,WEINBERG RA.Hallmarks of cancer:the next generation［J］.Cell,2011,144(5):646-674.
［31］ATSUMI T,CHESNEY J,METZ C,et al.High expression of inducible 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase(iPFK-2;PFKFB3) in human cancers［J］.Cancer Res,2002,62(20):5881-5887.
［32］LONG Q,ZOU X,SONG Y,et al.PFKFB3/HIF-1alpha feedback loop modulates sorafenib resistance in hepatocellular carcinoma cells［J］.Biochem Biophys Res Commun,2019,513(3):642-650.
［33］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.
［34］DOU Q,GRANT AK,CALLAHAN C,et al.PFKFB3-mediated pro-glycolytic shift in hepatocellular carcinoma proliferation［J］.Cell Mol Gastroenterol Hepatol,2023,15(1):61-75.

Memo

Memo:
陕西省重点研发计划项目（编号：2021SF-225）;广东省深圳市南山区科技计划项目（编号：NS2021026）；华中科技大学协和深圳医院院级课题（编号：YN2021021）
Last Update: 1900-01-01