p53/miR-34a调控网络在肿瘤中的作用
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摘要
MicroRNA是重要的调控分子,长约22 nt,属于非编码RNA,对肿瘤的发生和发展起着重要的作用。miR-34a是研究比较清楚的microRNA,目前认为是重要的抑癌micro RNA。p53是一个重要的抑癌基因。p53与miR-34a形成的正反馈调控网络具有抑制肿瘤细胞生长、转移及抑制肿瘤干细胞的功能。现综述p53/miR-34a调控网络研究的最新进展,并探讨其在肿瘤诊断及治疗中的应用。
MicroRNAs(miRNAs) are small noncoding RNAs with the length of ~22 nucleotides. They play important roles in tumorgenesis. miR-34 a is considered to be a tumor suppressor. p53 is a tumor suppressor. The positive feedback of p53/miR-34 a could inhibit tumor cell growth and migration. This review will summarize the progress of p53/miR-34 a network in tumor, and also discuss its application in diagnosis and treatment of cancer.
MicroRNAs(miRNAs) are small noncoding RNAs with the length of ~22 nucleotides. They play important roles in tumorgenesis. miR-34 a is considered to be a tumor suppressor. p53 is a tumor suppressor. The positive feedback of p53/miR-34 a could inhibit tumor cell growth and migration. This review will summarize the progress of p53/miR-34 a network in tumor, and also discuss its application in diagnosis and treatment of cancer.
引文
[1]He L,Hannon GJ.Micro RNAs:small RNAs with a big role in gene regulation.Nat Rev Genet,2004,5:522-31
[2]Shyu AB,Wilkinson MF,van Hoof A.Messenger RNA regulation:to translate or to degrade.EMBO J,2008,27:471-81
[3]Neely LA,Patel S,Garver J.A single-molecule method for the quantitation of micro RNA gene expression.Nat Methods,2006,3:41-6
[4]Berezikov E,Cuppen E,Plasterk RH.Approaches to micro RNA discovery.Nat Genet,2006,38:S2-7
[5]Kandoth C,Mc Lellan MD,Vandin F,et al.Mutational landscape and significance across 12 major cancer types.Nature,2013,502:333-9
[6]Vogelstein B,Lane D,Levine AJ.Surfing the p53 network.Nature.2000,408:307-10
[7]Hermeking H.p53 enters the micro RNA world.Cancer Cell,2007,12:414-8
[8]Yamakuchi M,Ferlito M,Lowenstein CJ.mi R-34a repression of SIRT1 regulates apoptosis.Proc Natl Acad Sci USA,2008,105:13421-6
[9]Chang TC,Wentzel EA,Kent OA,et al.Transactivation of mi R-34a by p53 broadly influences gene expression and promotes apoptosis.Mol Cell,2007,26:745-52
[10]He L,He X,Lim LP,et al.A micro RNA component of the p53 tumour suppressor network.Nature,2007,447:1130-4
[11]Bommer GT,Gerin I,Feng Y,et al.p53-mediated activation of mi RNA34 candidate tumor-suppressor genes.Current Biol,2007,17:1298-307
[12]Hong JH,Roh KS,Suh SS,et al.The expression of micro RNA-34a is inversely correlated with c-MET and CDK6 and has a prognostic significance in lung adenocarcinoma patients.Tumour Biol,2015,36:9327-37
[13]Hargraves KG,He L,Firestone GL.Phytochemical regulation of the tumor suppressive micro RNA,mi R-34a,by p53-dependent and independent responses in human breast cancer cells.Mol Carcinogen,2016,55:486-98
[14]Kiyonari S,Iimori M,Matsuoka K,et al.The 1,2-Diaminocyclohexane carrier ligand in oxaliplatin induces p53-dependent transcriptional repression of factors involved in thymidylate biosynthesis.Mol Cancer Ther,2015,14:2332-42
[15]Ichimura A,Ruike Y,Terasawa K,et al.Micro RNA-34a inhibits cell proliferation by repressing mitogen-activated protein kinase kinase 1 during megakaryocytic differentiation of K562 cells.Mol Pharmacol,2010,77:1016-24
[16]Choi SE,Fu T,Seok S,et al.Elevated micro RNA-34a in obesity reduces NAD+levels and SIRT1 activity by directly targeting NAMPT.Aging Cell,2013,12:1062-72
[17]Liu Y,Li X,Zhu S,et al.Ectopic expression of mi R-494inhibited the proliferation,invasion and chemoresistance of pancreatic cancer by regulating SIRT1 and c-Myc.Gene Ther,2015,22:729-38
[18]Menssen A,Hermeking H.c-MYC and SIRT1 locked in a vicious cycle.Oncotarget,2012,3:112-3
[19]Marshall GM,Liu PY,Gherardi S,et al.SIRT1 promotes N-Myc oncogenesis through a positive feedback loop involving the effects of MKP3 and ERK on N-Myc protein stability.PLo S Genet,2011,7:e1002135
[20]Long Z,Wang B,Tao D,et al.Hypofractionated radiotherapy induces mi R-34a expression and enhances apoptosis in human nasopharyngeal carcinoma cells.Int J Mol Med,2014,34:1388-94
[21]Garofalo M,Jeon YJ,Nuovo GJ,et al.Mi R-34a/c-dependent PDGFR-ɑ/βdownregulation inhibits tumorigenesis and enhances TRAIL-induced apoptosis in lung cancer.PLo S One,2013,8:e67581
[22]Hau A,Ceppi P,Peter ME.CD95 is part of a let-7/p53/mi R-34 regulatory network.PLo S One,2012,7:e49636
[23]Li L,Yuan L,Luo J,Gao J,et al.Mi R-34a inhibits proliferation and migration of breast cancer through down-regulation of Bcl-2 and SIRT1.Clin Exp Med,2013,13:109-17
[24]Muppala S,Mudduluru G,Leupold JH,et al.CD24 induces expression of the oncomir mi R-21 via Src,and CD24and Src are both post-transcriptionally downregulated by the tumor suppressor mi R-34a.PLo S One,2013,8:e59563
[25]Zhao G,Guo J,Li D,et al.Micro RNA-34a suppresses cell proliferation by targeting LMTK3 in human breast cancer mcf-7 cell line.DNA Cell Biol,2013,32:699-707
[26]Mohan M,Kumar V,Lackner AA,et al.Dysregulated mi R-34a-SIRT1-acetyl p65 axis is a potential mediator of immune activation in the colon during chronic simian immunodeficiency virus infection of rhesus macaques.J Immunol,2015,194:291-306
[27]Mandke P,Wyatt N,Fraser J,et al.Micro RNA-34a modulates MDM4 expression via a target site in the open reading frame.PLo S One,2012,7:e42034
[28]Siemens H,Jackstadt R,Kaller M,et al.Repression of c-Kit by p53 is mediated by mi R-34 and is associated with reduced chemoresistance,migration and stemness.Oncotarget,2013,4:1399-415
[29]Geng D,Song X,Ning F,et al.Mi R-34a inhibits viability and invasion of human papillomavirus-positive cervical cancer cells by targeting E2F3 and regulating survivin.Int J Gynecol Cancer,2015,25:707-13
[30]Kashat M,Azzouz L,Sarkar SH,et al.Inactivation of AR and Notch-1 signaling by mi R-34a attenuates prostate cancer aggressiveness.Am J Transl Res,2012,4:432-42
[31]Mudduluru G,Ceppi P,Kumarswamy R,et al.Regulation of Axl receptor tyrosine kinase expression by mi R-34a and mi R-199a/b in solid cancer.Oncogene,2011,30:2888-99
[32]Nie J,Ge X,Geng Y,et al.mi R-34a inhibits the migration and invasion of esophageal squamous cell carcinoma by targeting Yin Yang-1.Oncology Rep,2015,34:311-7
[33]Garofalo M,Jeon YJ,Nuovo GJ,et al.Correction:Mi R-34a/c-dependent PDGFR-ɑ/βdownregulation inhibits tumorigenesis and enhances TRAIL-induced apoptosis in lung cancer.PLo S One,2015,10:e0131729
[34]Xu X,Chen W,Miao R,et al.mi R-34a induces cellular senescence via modulation of telomerase activity in human hepatocellular carcinoma by targeting Fox M1/c-Myc pathway.Oncotarget,2015,6:3988-4004
[35]Menges CW,Kadariya Y,Altomare D,et al.Tumor suppressor alterations cooperate to drive aggressive mesotheliomas with enriched cancer stem cells via a p53-mi R-34a-c-Met axis.Cancer Res,2014,74:1261-71
[36]De Craene B,Berx G.Regulatory networks defining EMT during cancer initiation and progression.Nat Rev Cancer,2013,13:97-110
[37]Siemens H,Jackstadt R,Hunten S,et al.mi R-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions.Cell Cycle,2011,10:4256-71
[38]Du R,Sun W,Xia L,et al.Hypoxia-induced down-regulation of micro RNA-34a promotes EMT by targeting the Notch signaling pathway in tubular epithelial cells.PLo S One,2012,7:e30771
[39]Kim T,Veronese A,Pichiorri F,et al.p53 regulates epithelial-mesenchymal transition through micro RNAs targeting ZEB1 and ZEB2.J Exp Med,2011,208:875-83
[40]Burk U,Schubert J,Wellner U,et al.A reciprocal repression between ZEB1 and members of the mi R-200 family promotes EMT and invasion in cancer cells.EMBO Rep,2008,9:582-9
[41]Ahn YH,Gibbons DL,Chakravarti D,et al.ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating mi R-34a expression.J Clin Invest 2012,122:3170-83
[42]Hahn S,Jackstadt R,Siemens H,et al.SNAIL and mi R-34a feed-forward regulation of ZNF281/ZBP99 promotes epithelial-mesenchymal transition.EMBO J,2013,32:3079-95
[43]Dang Y,Luo D,Rong M,et al.Underexpression of mi R-34a in hepatocellular carcinoma and its contribution towards enhancement of proliferating inhibitory effects of agents targeting c-MET.PLo S One,2013,8:e61054
[44]Siemens H,Neumann J,Jackstadt R,et al.Detection of mi R-34a promoter methylation in combination with ele-vated expression of c-Met andβ-catenin predicts distant metastasis of colon cancer.Clin Cancer Res,2013,19:710-20
[45]Yang S,Li Y,Gao J,Zhang T,et al.Micro RNA-34 suppresses breast cancer invasion and metastasis by directly targeting Fra-1.Oncogene,2013,32:4294-303
[46]Yan K,Gao J,Yang T,et al.Micro RNA-34a inhibits the proliferation and metastasis of osteosarcoma cells both in vitro and in vivo.PLo S One,2012,7:e33778
[47]Kong D,Heath E,Chen W,et al.Epigenetic silencing of mi R-34a in human prostate cancer cells and tumor tissue specimens can be reversed by BR-DIM treatment.Am J Transl Res,2012,4:14-23
[48]Zhou JY,Chen X,Zhao J,et al.Micro RNA-34a overcomes HGF-mediated gefitinib resistance in EGFR mutant lung cancer cells partly by targeting MET.Cancer Lett,2014,351:265-71
[49]Kaller M,Liffers ST,Oeljeklaus S,et al.Genome-wide characterization of mi R-34a induced changes in protein and m RNA expression by a combined pulsed SILAC and microarray analysis.Mol Cell Proteomics,2011,10:M111010462
[50]Mao B,Zhao G,Lv X,et al.Sirt1 deacetylates c-Myc and promotes c-Myc/Max association.Int J Biochem Cell Biol,2011,43:1573-81
[51]Simmons GE Jr,Pruitt WM,Pruitt K.Diverse roles of SIRT1 in cancer biology and lipid metabolism.Int J Mol Sci,2015,16:950-65
[52]Liu C,Kelnar K,Liu B,et al.The micro RNA mi R-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44.Nat Med,2011,17:211-5
[53]Bu P,Chen KY,Chen JH,et al.A micro RNA mi R-34a-regulated bimodal switch targets Notch in colon cancer stem cells.Cell Stem Cell,2013,12:602-15
[54]Winton DJ.mi R-34a sets the“sweet spot”for notch in colorectal cancer stem cells.Cell Stem Cell,2013,12:499-501
[55]de Antonellis P,Medaglia C,Cusanelli E,et al.Mi R-34a targeting of Notch ligand delta-like 1 impairs CD15+/CD133+tumor-propagating cells and supports neural differentiation in medulloblastoma.PLo S One,2011,6:e24584
[56]Pang RT,Leung CO,Lee CL,et al.Micro RNA-34a is a tumor suppressor in choriocarcinoma via regulation of Delta-like1.BMC Cancer,2013,13:25
[57]Kang L,Mao J,Tao Y,et al.Micro RNA-34a suppresses the breast cancer stem cell-like characteristics by downregulating Notch1 pathway.Cancer Sci,2015,106:700-8
[58]Zhao J,Kelnar K,Bader AG.In-depth analysis shows synergy between erlotinib and mi R-34a.PLo S One,2014,9:e89105
[2]Shyu AB,Wilkinson MF,van Hoof A.Messenger RNA regulation:to translate or to degrade.EMBO J,2008,27:471-81
[3]Neely LA,Patel S,Garver J.A single-molecule method for the quantitation of micro RNA gene expression.Nat Methods,2006,3:41-6
[4]Berezikov E,Cuppen E,Plasterk RH.Approaches to micro RNA discovery.Nat Genet,2006,38:S2-7
[5]Kandoth C,Mc Lellan MD,Vandin F,et al.Mutational landscape and significance across 12 major cancer types.Nature,2013,502:333-9
[6]Vogelstein B,Lane D,Levine AJ.Surfing the p53 network.Nature.2000,408:307-10
[7]Hermeking H.p53 enters the micro RNA world.Cancer Cell,2007,12:414-8
[8]Yamakuchi M,Ferlito M,Lowenstein CJ.mi R-34a repression of SIRT1 regulates apoptosis.Proc Natl Acad Sci USA,2008,105:13421-6
[9]Chang TC,Wentzel EA,Kent OA,et al.Transactivation of mi R-34a by p53 broadly influences gene expression and promotes apoptosis.Mol Cell,2007,26:745-52
[10]He L,He X,Lim LP,et al.A micro RNA component of the p53 tumour suppressor network.Nature,2007,447:1130-4
[11]Bommer GT,Gerin I,Feng Y,et al.p53-mediated activation of mi RNA34 candidate tumor-suppressor genes.Current Biol,2007,17:1298-307
[12]Hong JH,Roh KS,Suh SS,et al.The expression of micro RNA-34a is inversely correlated with c-MET and CDK6 and has a prognostic significance in lung adenocarcinoma patients.Tumour Biol,2015,36:9327-37
[13]Hargraves KG,He L,Firestone GL.Phytochemical regulation of the tumor suppressive micro RNA,mi R-34a,by p53-dependent and independent responses in human breast cancer cells.Mol Carcinogen,2016,55:486-98
[14]Kiyonari S,Iimori M,Matsuoka K,et al.The 1,2-Diaminocyclohexane carrier ligand in oxaliplatin induces p53-dependent transcriptional repression of factors involved in thymidylate biosynthesis.Mol Cancer Ther,2015,14:2332-42
[15]Ichimura A,Ruike Y,Terasawa K,et al.Micro RNA-34a inhibits cell proliferation by repressing mitogen-activated protein kinase kinase 1 during megakaryocytic differentiation of K562 cells.Mol Pharmacol,2010,77:1016-24
[16]Choi SE,Fu T,Seok S,et al.Elevated micro RNA-34a in obesity reduces NAD+levels and SIRT1 activity by directly targeting NAMPT.Aging Cell,2013,12:1062-72
[17]Liu Y,Li X,Zhu S,et al.Ectopic expression of mi R-494inhibited the proliferation,invasion and chemoresistance of pancreatic cancer by regulating SIRT1 and c-Myc.Gene Ther,2015,22:729-38
[18]Menssen A,Hermeking H.c-MYC and SIRT1 locked in a vicious cycle.Oncotarget,2012,3:112-3
[19]Marshall GM,Liu PY,Gherardi S,et al.SIRT1 promotes N-Myc oncogenesis through a positive feedback loop involving the effects of MKP3 and ERK on N-Myc protein stability.PLo S Genet,2011,7:e1002135
[20]Long Z,Wang B,Tao D,et al.Hypofractionated radiotherapy induces mi R-34a expression and enhances apoptosis in human nasopharyngeal carcinoma cells.Int J Mol Med,2014,34:1388-94
[21]Garofalo M,Jeon YJ,Nuovo GJ,et al.Mi R-34a/c-dependent PDGFR-ɑ/βdownregulation inhibits tumorigenesis and enhances TRAIL-induced apoptosis in lung cancer.PLo S One,2013,8:e67581
[22]Hau A,Ceppi P,Peter ME.CD95 is part of a let-7/p53/mi R-34 regulatory network.PLo S One,2012,7:e49636
[23]Li L,Yuan L,Luo J,Gao J,et al.Mi R-34a inhibits proliferation and migration of breast cancer through down-regulation of Bcl-2 and SIRT1.Clin Exp Med,2013,13:109-17
[24]Muppala S,Mudduluru G,Leupold JH,et al.CD24 induces expression of the oncomir mi R-21 via Src,and CD24and Src are both post-transcriptionally downregulated by the tumor suppressor mi R-34a.PLo S One,2013,8:e59563
[25]Zhao G,Guo J,Li D,et al.Micro RNA-34a suppresses cell proliferation by targeting LMTK3 in human breast cancer mcf-7 cell line.DNA Cell Biol,2013,32:699-707
[26]Mohan M,Kumar V,Lackner AA,et al.Dysregulated mi R-34a-SIRT1-acetyl p65 axis is a potential mediator of immune activation in the colon during chronic simian immunodeficiency virus infection of rhesus macaques.J Immunol,2015,194:291-306
[27]Mandke P,Wyatt N,Fraser J,et al.Micro RNA-34a modulates MDM4 expression via a target site in the open reading frame.PLo S One,2012,7:e42034
[28]Siemens H,Jackstadt R,Kaller M,et al.Repression of c-Kit by p53 is mediated by mi R-34 and is associated with reduced chemoresistance,migration and stemness.Oncotarget,2013,4:1399-415
[29]Geng D,Song X,Ning F,et al.Mi R-34a inhibits viability and invasion of human papillomavirus-positive cervical cancer cells by targeting E2F3 and regulating survivin.Int J Gynecol Cancer,2015,25:707-13
[30]Kashat M,Azzouz L,Sarkar SH,et al.Inactivation of AR and Notch-1 signaling by mi R-34a attenuates prostate cancer aggressiveness.Am J Transl Res,2012,4:432-42
[31]Mudduluru G,Ceppi P,Kumarswamy R,et al.Regulation of Axl receptor tyrosine kinase expression by mi R-34a and mi R-199a/b in solid cancer.Oncogene,2011,30:2888-99
[32]Nie J,Ge X,Geng Y,et al.mi R-34a inhibits the migration and invasion of esophageal squamous cell carcinoma by targeting Yin Yang-1.Oncology Rep,2015,34:311-7
[33]Garofalo M,Jeon YJ,Nuovo GJ,et al.Correction:Mi R-34a/c-dependent PDGFR-ɑ/βdownregulation inhibits tumorigenesis and enhances TRAIL-induced apoptosis in lung cancer.PLo S One,2015,10:e0131729
[34]Xu X,Chen W,Miao R,et al.mi R-34a induces cellular senescence via modulation of telomerase activity in human hepatocellular carcinoma by targeting Fox M1/c-Myc pathway.Oncotarget,2015,6:3988-4004
[35]Menges CW,Kadariya Y,Altomare D,et al.Tumor suppressor alterations cooperate to drive aggressive mesotheliomas with enriched cancer stem cells via a p53-mi R-34a-c-Met axis.Cancer Res,2014,74:1261-71
[36]De Craene B,Berx G.Regulatory networks defining EMT during cancer initiation and progression.Nat Rev Cancer,2013,13:97-110
[37]Siemens H,Jackstadt R,Hunten S,et al.mi R-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions.Cell Cycle,2011,10:4256-71
[38]Du R,Sun W,Xia L,et al.Hypoxia-induced down-regulation of micro RNA-34a promotes EMT by targeting the Notch signaling pathway in tubular epithelial cells.PLo S One,2012,7:e30771
[39]Kim T,Veronese A,Pichiorri F,et al.p53 regulates epithelial-mesenchymal transition through micro RNAs targeting ZEB1 and ZEB2.J Exp Med,2011,208:875-83
[40]Burk U,Schubert J,Wellner U,et al.A reciprocal repression between ZEB1 and members of the mi R-200 family promotes EMT and invasion in cancer cells.EMBO Rep,2008,9:582-9
[41]Ahn YH,Gibbons DL,Chakravarti D,et al.ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating mi R-34a expression.J Clin Invest 2012,122:3170-83
[42]Hahn S,Jackstadt R,Siemens H,et al.SNAIL and mi R-34a feed-forward regulation of ZNF281/ZBP99 promotes epithelial-mesenchymal transition.EMBO J,2013,32:3079-95
[43]Dang Y,Luo D,Rong M,et al.Underexpression of mi R-34a in hepatocellular carcinoma and its contribution towards enhancement of proliferating inhibitory effects of agents targeting c-MET.PLo S One,2013,8:e61054
[44]Siemens H,Neumann J,Jackstadt R,et al.Detection of mi R-34a promoter methylation in combination with ele-vated expression of c-Met andβ-catenin predicts distant metastasis of colon cancer.Clin Cancer Res,2013,19:710-20
[45]Yang S,Li Y,Gao J,Zhang T,et al.Micro RNA-34 suppresses breast cancer invasion and metastasis by directly targeting Fra-1.Oncogene,2013,32:4294-303
[46]Yan K,Gao J,Yang T,et al.Micro RNA-34a inhibits the proliferation and metastasis of osteosarcoma cells both in vitro and in vivo.PLo S One,2012,7:e33778
[47]Kong D,Heath E,Chen W,et al.Epigenetic silencing of mi R-34a in human prostate cancer cells and tumor tissue specimens can be reversed by BR-DIM treatment.Am J Transl Res,2012,4:14-23
[48]Zhou JY,Chen X,Zhao J,et al.Micro RNA-34a overcomes HGF-mediated gefitinib resistance in EGFR mutant lung cancer cells partly by targeting MET.Cancer Lett,2014,351:265-71
[49]Kaller M,Liffers ST,Oeljeklaus S,et al.Genome-wide characterization of mi R-34a induced changes in protein and m RNA expression by a combined pulsed SILAC and microarray analysis.Mol Cell Proteomics,2011,10:M111010462
[50]Mao B,Zhao G,Lv X,et al.Sirt1 deacetylates c-Myc and promotes c-Myc/Max association.Int J Biochem Cell Biol,2011,43:1573-81
[51]Simmons GE Jr,Pruitt WM,Pruitt K.Diverse roles of SIRT1 in cancer biology and lipid metabolism.Int J Mol Sci,2015,16:950-65
[52]Liu C,Kelnar K,Liu B,et al.The micro RNA mi R-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44.Nat Med,2011,17:211-5
[53]Bu P,Chen KY,Chen JH,et al.A micro RNA mi R-34a-regulated bimodal switch targets Notch in colon cancer stem cells.Cell Stem Cell,2013,12:602-15
[54]Winton DJ.mi R-34a sets the“sweet spot”for notch in colorectal cancer stem cells.Cell Stem Cell,2013,12:499-501
[55]de Antonellis P,Medaglia C,Cusanelli E,et al.Mi R-34a targeting of Notch ligand delta-like 1 impairs CD15+/CD133+tumor-propagating cells and supports neural differentiation in medulloblastoma.PLo S One,2011,6:e24584
[56]Pang RT,Leung CO,Lee CL,et al.Micro RNA-34a is a tumor suppressor in choriocarcinoma via regulation of Delta-like1.BMC Cancer,2013,13:25
[57]Kang L,Mao J,Tao Y,et al.Micro RNA-34a suppresses the breast cancer stem cell-like characteristics by downregulating Notch1 pathway.Cancer Sci,2015,106:700-8
[58]Zhao J,Kelnar K,Bader AG.In-depth analysis shows synergy between erlotinib and mi R-34a.PLo S One,2014,9:e89105