长链非编码RNA对原发性肝癌中糖酵解途径的影响机制
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摘要
原发性肝癌发病机制复杂,具有起病隐匿、恶性程度高、预后差等特点。而肿瘤细胞与正常细胞的区别之一在于糖代谢途径的改变,肿瘤细胞优先选择糖酵解途径提供能量。有氧糖酵解则常与原发性肝癌的进展及预后不良有关。长链非编码RNA在众多肿瘤中通过调节糖摄取率、糖酵解酶的表达及活性,影响糖酵解途径,并在原发性肝癌的发生及进展中起着重要的调节作用,提示其可以作为肝癌的治疗靶点。总结了长链非编码RNA对原发性肝癌及糖代谢的影响机制,旨在为原发性肝癌寻找潜在有效的靶向治疗。
Primary liver cancer is a common malignant tumor with complex pathogeneses and has the features of insidious onset,high degree of malignancy,and poor prognosis. The change in glycolytic pathway is one of the most important differences between tumor cells and normal cells,and tumor cells prefer to generate energy from glycolysis. Aerobic glycolysis is often associated with the progression and poor prognosis of primary liver cancer. Long non-coding RNAs(lncRNAs) can influence the glycolysis pathway in many tumors by regulating glucose uptake and the expression and activation of glycolytic enzymes and thus play an important role in the development and progression of primary liver cancer,which suggests that lncRNAs can be used as a therapeutic target for liver cancer. This article summarizes the influence of lncRNAs on primary liver cancer and glucose metabolism and related mechanisms,so as to find potential and effective targeted therapies for primary liver cancer.
Primary liver cancer is a common malignant tumor with complex pathogeneses and has the features of insidious onset,high degree of malignancy,and poor prognosis. The change in glycolytic pathway is one of the most important differences between tumor cells and normal cells,and tumor cells prefer to generate energy from glycolysis. Aerobic glycolysis is often associated with the progression and poor prognosis of primary liver cancer. Long non-coding RNAs(lncRNAs) can influence the glycolysis pathway in many tumors by regulating glucose uptake and the expression and activation of glycolytic enzymes and thus play an important role in the development and progression of primary liver cancer,which suggests that lncRNAs can be used as a therapeutic target for liver cancer. This article summarizes the influence of lncRNAs on primary liver cancer and glucose metabolism and related mechanisms,so as to find potential and effective targeted therapies for primary liver cancer.
引文
[1]BRAY F,FERLAY J,SOERJOMATARAM I,et al.Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CACancer J Clin,2018,68(6):394-424.
[2]WONG CM,TSANG FH,NG IO.Non-coding RNAs in hepatocellular carcinoma:Molecular functions and pathological implications[J].Nat Rev Gastroenterol Hepatol,2018,15(3):137-151.
[3]DHANASEKARAN R,LIMAYE A,CABRERA R.Hepatocellular carcinoma:Current trends in worldwide epidemiology,risk factors,diagnosis,and therapeutics[J].Hepat Med,2012,4:19-37.
[4]WARBURG O.The chemical constitution of respiration ferment[J].Science,1928,68(1767):437-443.
[5]LUNT S,VANDER HEIDEN M.Aerobic glycolysis:Meeting the metabolic requirements of cell proliferation[J].Annu Rev Cell Dev Biol,2011,27:441-464.
[6]LU J,TAN M,CAI Q.The Warburg effect in tumor progression:Mitochondrial oxidative metabolism as an anti-metastasis mechanism[J].Cancer Lett,2015,356(2 Pt A):156-164.
[7]FAN C,TANG Y,WANG J,et al.Role of long non-coding RNAs in glucose metabolism in cancer[J].Mol Cancer,2017,16(1):130.
[8]GANAPATHY-KANNIAPPAN S,GESCHWIND JF.Tumor glycolysis as a target for cancer therapy:Progress and prospects[J].Molecular cancer,2013,12:152.
[9]LI M,JIN R,WANG W,et al.STAT3 regulates glycolysis via targeting hexokinase 2 in hepatocellular carcinoma cells[J].Oncotarget,2017,8(15):24777-24784.
[10]DEWAAL D,NOGUEIRA V,TERRY AR,et al.Hexokinase-2depletion inhibits glycolysis and induces oxidative phosphorylation in hepatocellular carcinoma and sensitizes to metformin[J].Nat Commun,2018,9(1):446.
[11]CHESNEY J,CLARK J,KLARER A,et al.Fructose-2,6-bisphosphate synthesis by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4(PFKFB4)is required for the glycolytic response to hypoxia and tumor growth[J].Oncotarget,2014,5(16):6670-6686.
[12]SHI L,PAN H,LIU Z,et al.Roles of PFKFB3 in cancer[J].Signal Transduct Target Ther,2017,2:17044.
[13]SHI W,ZHU X,WANG C,et al.PFKFB3 blockade inhibits hepatocellular carcinoma growth by impairing DNA repair through AKT[J].Cel Death Dis,2018,9(4):428.
[14]SHU Y,LU Y,PANG X,et al.Phosphorylation of PPARgamma at Ser84 promotes glycolysis and cell proliferation in hepatocellular carcinoma by targeting PFKFB4[J].Oncotarget,2016,7(47):76984-76994.
[15]DAYTON T,JACKS T,van der HEIDEN M.PKM2,cancer metabolism,and the road ahead[J].EMBO Rep,2016,17(12):1721-1730.
[16]LUO W,SEMENZA G.Emerging roles of PKM2 in cell metabolism and cancer progression[J].Trends Endocrinol Metab,2012,23(11):560-566.
[17]WONG C,AU S,TSE A,et al.Switching of pyruvate kinase isoform L to M2 promotes metabolic reprogramming in hepatocarcinogenesis[J].PLo S One,2014,9(12):e115036.
[18]PENG Z,LIU C,WU M.New insights into long noncoding RNAs and their roles in glioma[J].Mol Cancer,2018,17(1):61.
[19]SUN M,KRAUS W.From discovery to function:The expanding roles of long noncoding RNAs in physiology and disease[J].Endocr Rev,2015,36(1):25-64.
[20]WANG K,CHANG H.Molecular mechanisms of long noncoding RNAs[J].Mol Cell,2011,43(6):904-914.
[21]WANG TH,YU CC,LIN YS,et al.Long noncoding RNA CPS1-IT1 suppresses the metastasis of hepatocellular carcinoma by regulating HIF-1αactivity and inhibiting epithelial-mesenchymal transition[J].Oncotarget,2016,7(28):43588-43603.
[22]HU JL,AN YL.The relationship between long non-coding RNA and hepatocellular carcinoma[J].Ogran Transplantation,2017,8(3):242-245.(in Chinese)胡建兰,安玉玲.长链非编码RNA与肝癌[J].器官移植,2017,8(3):242-245.
[23]LIN Y,WU M,HUANG Y,et al.Taurine up-regulated gene 1functions as a master regulator to coordinate glycolysis and metastasis in hepatocellular carcinoma[J].Hepatology,2018,67(1):188-203.
[24]LI Y,GUO D,ZHAO Y,et al.Long non-coding RNA SNHG5promotes human hepatocellular carcinoma progression by regulating miR-26a-5p/GSK3βsignal pathway[J].Cell Death Dis,2018,9(9):888.
[25]HUANG Y,XIANG B,LIU Y,et al.LncRNA CDKN2B-AS1promotes tumor growth and metastasis of human hepatocellular carcinoma by targeting let-7c-5p/NAP1L1 axis[J].Cancer Lett,2018,437:56-66.
[26]WANG Y,SUN L,WANG L,et al.Long non-coding RNADSCR8 acts as a molecular sponge for miR-485-5p to activate Wnt/β-catenin signal pathway in hepatocellular carcinoma[J].Cell Death Dis,2018,9(9):851.
[27]WANG H,KE J,GUO Q,et al.Long non-coding RNA CRNDEpromotes the proliferation,migration and invasion of hepatocellular carcinoma cells through miR-217/MAPK1 axis[J].J Cel Mol Med,2018,22(12):5862-5876.
[28]SUN Q,HU B,FU P,et al.Long non-coding RNA00607 as a tumor suppressor by modulating NF-κB p65/p53 signaling axis in hepatocellular carcinoma[J].Carcinogenesis,2018,39(12):1438-1446.
[29]ZHANG D,ZOU X,CAO C,et al.Identification and functional characterization of long non-coding RNA as a tumor suppressor for hepatocellular carcinoma[J].Theranostics,2018,8(14):3751-3765.
[30]TAKAHASHI K,YAN I,HAGA H,et al.Modulation of hypoxia-signaling pathways by extracellular linc-RoR[J].J Cell Sci,2014,127(Pt 7):1585-1594.
[31]YANG F,ZHANG H,MEI Y,et al.Reciprocal regulation of HIF-1αand lincRNA-p21 modulates the Warburg effect[J].Mol Cell,2014,53(1):88-100.
[32]XIANG S,GU H,JIN L,et al.LncRNA IDH1-AS1 links the functions of c-Myc and HIF1αvia IDH1 to regulate the Warburg effect[J].Proc Natl Acad Sci USA,2018,115(7):e1465-e1474.
[33]ZHENG X,HAN H,LIU GP,et al.LncRNA wires up Hippo and Hedgehog signaling to reprogramme glucose metabolism[J].EMBO J,2017,36(22):3325-3335.
[34]LI S,LI J,DAI W,et al.Genistein suppresses aerobic glycolysis and induces hepatocellular carcinoma cell death[J].Br JCancer,2017,117(10):1518-1528.
[35]LI S,DAI W,MO W,et al.By inhibiting PFKFB3,aspirin overcomes sorafenib resistance in hepatocellular carcinoma[J].Int J Cancer,2017,141(12):2571-2584.
[2]WONG CM,TSANG FH,NG IO.Non-coding RNAs in hepatocellular carcinoma:Molecular functions and pathological implications[J].Nat Rev Gastroenterol Hepatol,2018,15(3):137-151.
[3]DHANASEKARAN R,LIMAYE A,CABRERA R.Hepatocellular carcinoma:Current trends in worldwide epidemiology,risk factors,diagnosis,and therapeutics[J].Hepat Med,2012,4:19-37.
[4]WARBURG O.The chemical constitution of respiration ferment[J].Science,1928,68(1767):437-443.
[5]LUNT S,VANDER HEIDEN M.Aerobic glycolysis:Meeting the metabolic requirements of cell proliferation[J].Annu Rev Cell Dev Biol,2011,27:441-464.
[6]LU J,TAN M,CAI Q.The Warburg effect in tumor progression:Mitochondrial oxidative metabolism as an anti-metastasis mechanism[J].Cancer Lett,2015,356(2 Pt A):156-164.
[7]FAN C,TANG Y,WANG J,et al.Role of long non-coding RNAs in glucose metabolism in cancer[J].Mol Cancer,2017,16(1):130.
[8]GANAPATHY-KANNIAPPAN S,GESCHWIND JF.Tumor glycolysis as a target for cancer therapy:Progress and prospects[J].Molecular cancer,2013,12:152.
[9]LI M,JIN R,WANG W,et al.STAT3 regulates glycolysis via targeting hexokinase 2 in hepatocellular carcinoma cells[J].Oncotarget,2017,8(15):24777-24784.
[10]DEWAAL D,NOGUEIRA V,TERRY AR,et al.Hexokinase-2depletion inhibits glycolysis and induces oxidative phosphorylation in hepatocellular carcinoma and sensitizes to metformin[J].Nat Commun,2018,9(1):446.
[11]CHESNEY J,CLARK J,KLARER A,et al.Fructose-2,6-bisphosphate synthesis by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4(PFKFB4)is required for the glycolytic response to hypoxia and tumor growth[J].Oncotarget,2014,5(16):6670-6686.
[12]SHI L,PAN H,LIU Z,et al.Roles of PFKFB3 in cancer[J].Signal Transduct Target Ther,2017,2:17044.
[13]SHI W,ZHU X,WANG C,et al.PFKFB3 blockade inhibits hepatocellular carcinoma growth by impairing DNA repair through AKT[J].Cel Death Dis,2018,9(4):428.
[14]SHU Y,LU Y,PANG X,et al.Phosphorylation of PPARgamma at Ser84 promotes glycolysis and cell proliferation in hepatocellular carcinoma by targeting PFKFB4[J].Oncotarget,2016,7(47):76984-76994.
[15]DAYTON T,JACKS T,van der HEIDEN M.PKM2,cancer metabolism,and the road ahead[J].EMBO Rep,2016,17(12):1721-1730.
[16]LUO W,SEMENZA G.Emerging roles of PKM2 in cell metabolism and cancer progression[J].Trends Endocrinol Metab,2012,23(11):560-566.
[17]WONG C,AU S,TSE A,et al.Switching of pyruvate kinase isoform L to M2 promotes metabolic reprogramming in hepatocarcinogenesis[J].PLo S One,2014,9(12):e115036.
[18]PENG Z,LIU C,WU M.New insights into long noncoding RNAs and their roles in glioma[J].Mol Cancer,2018,17(1):61.
[19]SUN M,KRAUS W.From discovery to function:The expanding roles of long noncoding RNAs in physiology and disease[J].Endocr Rev,2015,36(1):25-64.
[20]WANG K,CHANG H.Molecular mechanisms of long noncoding RNAs[J].Mol Cell,2011,43(6):904-914.
[21]WANG TH,YU CC,LIN YS,et al.Long noncoding RNA CPS1-IT1 suppresses the metastasis of hepatocellular carcinoma by regulating HIF-1αactivity and inhibiting epithelial-mesenchymal transition[J].Oncotarget,2016,7(28):43588-43603.
[22]HU JL,AN YL.The relationship between long non-coding RNA and hepatocellular carcinoma[J].Ogran Transplantation,2017,8(3):242-245.(in Chinese)胡建兰,安玉玲.长链非编码RNA与肝癌[J].器官移植,2017,8(3):242-245.
[23]LIN Y,WU M,HUANG Y,et al.Taurine up-regulated gene 1functions as a master regulator to coordinate glycolysis and metastasis in hepatocellular carcinoma[J].Hepatology,2018,67(1):188-203.
[24]LI Y,GUO D,ZHAO Y,et al.Long non-coding RNA SNHG5promotes human hepatocellular carcinoma progression by regulating miR-26a-5p/GSK3βsignal pathway[J].Cell Death Dis,2018,9(9):888.
[25]HUANG Y,XIANG B,LIU Y,et al.LncRNA CDKN2B-AS1promotes tumor growth and metastasis of human hepatocellular carcinoma by targeting let-7c-5p/NAP1L1 axis[J].Cancer Lett,2018,437:56-66.
[26]WANG Y,SUN L,WANG L,et al.Long non-coding RNADSCR8 acts as a molecular sponge for miR-485-5p to activate Wnt/β-catenin signal pathway in hepatocellular carcinoma[J].Cell Death Dis,2018,9(9):851.
[27]WANG H,KE J,GUO Q,et al.Long non-coding RNA CRNDEpromotes the proliferation,migration and invasion of hepatocellular carcinoma cells through miR-217/MAPK1 axis[J].J Cel Mol Med,2018,22(12):5862-5876.
[28]SUN Q,HU B,FU P,et al.Long non-coding RNA00607 as a tumor suppressor by modulating NF-κB p65/p53 signaling axis in hepatocellular carcinoma[J].Carcinogenesis,2018,39(12):1438-1446.
[29]ZHANG D,ZOU X,CAO C,et al.Identification and functional characterization of long non-coding RNA as a tumor suppressor for hepatocellular carcinoma[J].Theranostics,2018,8(14):3751-3765.
[30]TAKAHASHI K,YAN I,HAGA H,et al.Modulation of hypoxia-signaling pathways by extracellular linc-RoR[J].J Cell Sci,2014,127(Pt 7):1585-1594.
[31]YANG F,ZHANG H,MEI Y,et al.Reciprocal regulation of HIF-1αand lincRNA-p21 modulates the Warburg effect[J].Mol Cell,2014,53(1):88-100.
[32]XIANG S,GU H,JIN L,et al.LncRNA IDH1-AS1 links the functions of c-Myc and HIF1αvia IDH1 to regulate the Warburg effect[J].Proc Natl Acad Sci USA,2018,115(7):e1465-e1474.
[33]ZHENG X,HAN H,LIU GP,et al.LncRNA wires up Hippo and Hedgehog signaling to reprogramme glucose metabolism[J].EMBO J,2017,36(22):3325-3335.
[34]LI S,LI J,DAI W,et al.Genistein suppresses aerobic glycolysis and induces hepatocellular carcinoma cell death[J].Br JCancer,2017,117(10):1518-1528.
[35]LI S,DAI W,MO W,et al.By inhibiting PFKFB3,aspirin overcomes sorafenib resistance in hepatocellular carcinoma[J].Int J Cancer,2017,141(12):2571-2584.