Naa10基因与肿瘤相关性的研究进展
|
摘要
N-末端α位乙酰基转移酶基因10(Naa10)广泛存在于真核生物细胞中,其编码的Naa10p是NatA复合物的催化亚基。Naa10p修饰新生蛋白质N末α位氨基酸残基乙酰化,进而通过介导mTOR、Ca~(2+)/MLCK、DNMT1、PGK1、PIX-蛋白等信号通路调控蛋白降解、细胞凋亡、增殖、迁移、浸润、血管生成等生物学过程。根据乙酰化底物的不同,Naa10p还在细胞凋亡的调控中起双重作用。研究发现Naa10p在肝癌、结直肠癌、乳腺癌、肺癌、前列腺癌等多种癌组织中过表达,而在癌旁组织中不表达或低表达,因肿瘤差异其预后意义不同。因此,Naa10可作为部分肿瘤诊断和预后的新型潜在生物标志物及治疗靶点。
N-α-terminal acetyltransferase gene 10(Naa10) is extensively expressed in eukaryotic cells, and its encoded Naa10p is the catalytic subunit of the NatA complex. Naa10p modifies the acetylation of aminophenol residues at the N-terminal-α of nascent protein; it regulates the biological processes such as protein degradation, apoptosis, cell proliferation, cell migration, infiltration and angiogenesis by mediating mTOR, Ca~(2+)/MLCK, DNMT1, PGK1 and PIX-protein pathways. Depending on the acetylated substrate, Naa10p also plays a dual role in the regulation of apoptosis. In the present studies, Naa10p is over-expressed in various cancer tissues such as liver cancer, colorectal cancer, breast cancer, lung cancer and prostate cancer, etc.; contrarily, low or non-expressed in paracancerous tissues. It correlates to diverse prognosis of different cancers. Therefore, it could be considered as a novel potential biomarker and therapeutic target for the diagnosis and prognosis of some cancers.
N-α-terminal acetyltransferase gene 10(Naa10) is extensively expressed in eukaryotic cells, and its encoded Naa10p is the catalytic subunit of the NatA complex. Naa10p modifies the acetylation of aminophenol residues at the N-terminal-α of nascent protein; it regulates the biological processes such as protein degradation, apoptosis, cell proliferation, cell migration, infiltration and angiogenesis by mediating mTOR, Ca~(2+)/MLCK, DNMT1, PGK1 and PIX-protein pathways. Depending on the acetylated substrate, Naa10p also plays a dual role in the regulation of apoptosis. In the present studies, Naa10p is over-expressed in various cancer tissues such as liver cancer, colorectal cancer, breast cancer, lung cancer and prostate cancer, etc.; contrarily, low or non-expressed in paracancerous tissues. It correlates to diverse prognosis of different cancers. Therefore, it could be considered as a novel potential biomarker and therapeutic target for the diagnosis and prognosis of some cancers.
引文
[1]Chen WQ,Zheng R,Zuo T,et al.National cancer incidence and mortality in China,2012[J].Chin J Cancer Res,2016,28(1):1-11.
[2]Silva RD,Martinho RG.Developmental roles of protein N-terminal acetylation[J].Proteomics,2015,15(14):2402-9.
[3]Myklebust LM,St?ve SI,Arnesen T.Naa10 in development and disease[J].Oncotarget,2015,6(33):34041-2.
[4]Dorfel MJ,Lyon GJ.The biological functions of Naa10-From amino-terminal acetylation to human disease[J].Gene,2015,567(2):103-31.
[5]Seo JH,Park JH,Lee EJ,et al.Autoacetylation regulates differentially the roles of ARD1 variants in tumorigenesis[J].Int JOncol,2015,46(1):99-106.
[6]Yu M,Gong J,Ma M,et al.Immunohistochemical analysis of human arrest-defective-1 expressed in cancers in vivo[J].Oncol Rep,2009,21(4):909-15.
[7]Polevoda B,Arnesen T,Sherman F.A synopsis of eukaryotic Nalpha-terminal acetyltransferases:nomenclature,subunits and substrates[J].BMC Proc,2009,3 Suppl 6:S2.
[8]Arnesen T,Thompson PR,Varhaug JE,et al.The protein acetyltransferase ARD1:a novel cancer drug target?[J].Curr Drug Targets,2008,8(7):545-53.
[9]Rope AF,Wang K,Evjenth R,et al.Using VAAST to identify an X-linked disorder resulting in lethality in male infants due to N-terminal acetyltransferase deficiency[J].Am J Hum Genet,2011,89(1):28-43.
[10]Mughal AA,Grieg Z,Skjellegrind H,et al.Knockdown of NAT12/NAA30 reduces tumorigenic features of glioblastomainitiating cells[J].Mol Cancer,2015,14:160.
[11]Pavlou D,Kirmizis A.Depletion of histone N-terminalacetyltransferase Naa40 induces p53-independent apoptosis in colorectal cancer cells via the mitochondrial pathway[J].Apoptosis,2016,21(3):298-311.
[12]Stove SI,Magin RS,Foyn H,et al.Crystal Structure of the GolgiAssociated Human Nalpha-Acetyltransferase 60 Reveals the Molecular Determinants for Substrate-Specific Acetylation[J].Structure,2016,24(7):1044-56.
[13]Reddi R,Saddanapu V,Chinthapalli DK,et al.Human Naa50Protein Displays Broad Substrate Specificity for Amino-terminal Acetylation:DETAILED STRUCTURAL AND BIOCHEMICALANALYSIS USING TETRAPEPTIDE LIBRARY[J].J Biol Chem,2016,291(39):20530-8.
[14]Weyer FA,Gumiero A,Lapouge K,et al.Structural basis of HypK regulating N-terminal acetylation by the NatA complex[J].Nat Commun,2017,8:15726.
[15]Lee KE,Heo JE,Kim JM,et al.N-Terminal Acetylation-Targeted N-End Rule Proteolytic System:The Ac/N-End Rule Pathway[J].Mol Cells,2016,39(3):169-78.
[16]Xu H,Jiang B,Meng L,et al.N-alpha-acetyltransferase 10protein inhibits apoptosis through RelA/p65-regulated MCL1expression[J].Carcinogenesis,2012,33(6):1193-202.
[17]Deng Y,Yang J,Luo F,et al.mTOR-mediated glycolysis contributes to the enhanced suppressive function of murine tumorinfiltrating monocytic myeloid-derived suppressor cells[J].Cancer Immunol Immunother,2018,67(9):1355-64.
[18]Yasumizu Y,Hongo H,Kosaka T,et al.PKM2 under hypoxic environment causes resistance to mTOR inhibitor in human castration resistant prostate cancer[J].Oncotarget,2018,9(45):27698-707.
[19]Kuo HP,Lee DF,Chen CT,et al.ARD1 stabilization of TSC2 suppresses tumorigenesis through the mTOR signaling pathway[J].Sci Signal,2010,3(108):ra9.
[20]Shin DH,Chun YS,Lee KH,et al.Arrest defective-1 controls tumor cell behavior by acetylating myosin light chain kinase[J].PLoS One,2009,4(10):e7451.
[21]Lee CF,Ou DS,Lee SB,et al.hNaa10p contributes to tumorigenesis by facilitating DNMT1-mediated tumor[J].J Clin Invest,2013,120(8):2920-30.
[22]Botrugno OA,Paris S,Za L,et al.Characterization of the endogenous GIT1-betaPIX complex,and identification of its association to membranes[J].Eur J Cell Biol,2006,85(1):35-46.
[23]Frank SR,Hansen SH.The PIX-GIT complex:a G protein signaling cassette in control of cell shape[J].Semin Cell Dev Biol,2008,19(3):234-44.
[24]Hua KT,Tan CT,Johansson G,et al.N-alpha-acetyltransferase 10protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity[J].Cancer Cell,2011,19(2):218-31.
[25]Qian X,Li X,Lu Z.Protein kinase activity of the glycolytic enzyme PGK1 regulates autophagy to promote tumorigenesis[J].Autophagy,2017,13(7):1246-7.
[26]Oh JH,Hyuna JY,Varshavskya A.Control of Hsp90 chaperone and its clients by N-terminal acetylation and the N-end rule pathway[J].Proc Natl Acad Sci U S A,2017,114(22):E4370-9.
[27]Shim JH,Chung YH,Kim JA,et al.Clinical implications of arrest-defective protein 1 expression in hepatocellular carcinoma:a novel predictor of microvascular invasion[J].Dig Dis,2012,30(6):603-8.
[28]Ren T,Jiang B,Jin G,et al.Generation of novel monoclonal antibodies and their application for detecting ARD1 expression in colorectal cancer[J].Cancer Lett,2008,264(1):83-92.
[29]Jiang B,Ren T,Dong B,et al.Peptide mimic isolated by autoantibody reveals human arrest defective 1 overexpression is associated with poor prognosis for colon cancer patients[J].Am JPathol,2010,77(3):1095-103.
[30]Yang H,Li Q,Niu J,et al.micro RNA-342-5p and mi R-608 inhibit colon cancer tumorigenesis by targeting NAA10[J].Oncotarget,2016,7(3):2709-20.
[31]Zeng Y,Min L,Han Y,et al.Inhibition of STAT5a by Naa10p contributes to decreased breast cancer metastasis[J].Carcinogenesis,2014,35(10):2244-53.
[32]Min L,Ma RL,Yuan H,et al.Combined Expression of Metastasis Related Markers Naa10p,SNCG and PRL-3 and its Prognostic Value in Breast Cancer Patients[J].Asian Pac J Cancer Prev,2015,16(7):2819-26.
[33]Zeng Y,Liu C,Dong B,et al.Inverse correlation between Naa10p and MMP-9 expression and the combined prognostic value in breast cancer patients[J].Med Oncol,2013,30(2):562.
[34]Wang ZH,Gong JL,Yu M,et al.Up-regulation of human arrestdefective 1 protein is correlated with metastatic phenotype and poor prognosis in breast cancer[J].Asian Pac J Cancer Prev,2011,12(8):1973-7.
[35]Wang Z,Wang Z,Guo J,et al.Inactivation of androgen-induced regulator ARD1 inhibits androgen receptor acetylation and prostate tumorigenesis[J].Proc Natl Acad Sci U S A,2012,109(8):3053-8.
[36]Chen X,Yang C,Xie S,et al.Long non-coding RNA GAS5 and ZFAS1 are prognostic markers involved in translation targeted by miR-940 in prostate cancer[J].Oncotarget,2018,9(1):1048-62.
[37]Zeng Y,Zheng J,Zhao J,et al.High expression of Naa10p associates with lymph node metastasis and predicts favorable prognosis of oral squamous cell carcinoma[J].Tumour Biol,2016,37(5):6719-28.
[38]Arnesen T,Gromyko D,Horvli O,et al.Expression of N-Acetyl Transferase Human and Human Arrest Defective 1 Proteins in Thyroid Neoplasms[J].Thyroid,2005,15(10):1131-6.
[2]Silva RD,Martinho RG.Developmental roles of protein N-terminal acetylation[J].Proteomics,2015,15(14):2402-9.
[3]Myklebust LM,St?ve SI,Arnesen T.Naa10 in development and disease[J].Oncotarget,2015,6(33):34041-2.
[4]Dorfel MJ,Lyon GJ.The biological functions of Naa10-From amino-terminal acetylation to human disease[J].Gene,2015,567(2):103-31.
[5]Seo JH,Park JH,Lee EJ,et al.Autoacetylation regulates differentially the roles of ARD1 variants in tumorigenesis[J].Int JOncol,2015,46(1):99-106.
[6]Yu M,Gong J,Ma M,et al.Immunohistochemical analysis of human arrest-defective-1 expressed in cancers in vivo[J].Oncol Rep,2009,21(4):909-15.
[7]Polevoda B,Arnesen T,Sherman F.A synopsis of eukaryotic Nalpha-terminal acetyltransferases:nomenclature,subunits and substrates[J].BMC Proc,2009,3 Suppl 6:S2.
[8]Arnesen T,Thompson PR,Varhaug JE,et al.The protein acetyltransferase ARD1:a novel cancer drug target?[J].Curr Drug Targets,2008,8(7):545-53.
[9]Rope AF,Wang K,Evjenth R,et al.Using VAAST to identify an X-linked disorder resulting in lethality in male infants due to N-terminal acetyltransferase deficiency[J].Am J Hum Genet,2011,89(1):28-43.
[10]Mughal AA,Grieg Z,Skjellegrind H,et al.Knockdown of NAT12/NAA30 reduces tumorigenic features of glioblastomainitiating cells[J].Mol Cancer,2015,14:160.
[11]Pavlou D,Kirmizis A.Depletion of histone N-terminalacetyltransferase Naa40 induces p53-independent apoptosis in colorectal cancer cells via the mitochondrial pathway[J].Apoptosis,2016,21(3):298-311.
[12]Stove SI,Magin RS,Foyn H,et al.Crystal Structure of the GolgiAssociated Human Nalpha-Acetyltransferase 60 Reveals the Molecular Determinants for Substrate-Specific Acetylation[J].Structure,2016,24(7):1044-56.
[13]Reddi R,Saddanapu V,Chinthapalli DK,et al.Human Naa50Protein Displays Broad Substrate Specificity for Amino-terminal Acetylation:DETAILED STRUCTURAL AND BIOCHEMICALANALYSIS USING TETRAPEPTIDE LIBRARY[J].J Biol Chem,2016,291(39):20530-8.
[14]Weyer FA,Gumiero A,Lapouge K,et al.Structural basis of HypK regulating N-terminal acetylation by the NatA complex[J].Nat Commun,2017,8:15726.
[15]Lee KE,Heo JE,Kim JM,et al.N-Terminal Acetylation-Targeted N-End Rule Proteolytic System:The Ac/N-End Rule Pathway[J].Mol Cells,2016,39(3):169-78.
[16]Xu H,Jiang B,Meng L,et al.N-alpha-acetyltransferase 10protein inhibits apoptosis through RelA/p65-regulated MCL1expression[J].Carcinogenesis,2012,33(6):1193-202.
[17]Deng Y,Yang J,Luo F,et al.mTOR-mediated glycolysis contributes to the enhanced suppressive function of murine tumorinfiltrating monocytic myeloid-derived suppressor cells[J].Cancer Immunol Immunother,2018,67(9):1355-64.
[18]Yasumizu Y,Hongo H,Kosaka T,et al.PKM2 under hypoxic environment causes resistance to mTOR inhibitor in human castration resistant prostate cancer[J].Oncotarget,2018,9(45):27698-707.
[19]Kuo HP,Lee DF,Chen CT,et al.ARD1 stabilization of TSC2 suppresses tumorigenesis through the mTOR signaling pathway[J].Sci Signal,2010,3(108):ra9.
[20]Shin DH,Chun YS,Lee KH,et al.Arrest defective-1 controls tumor cell behavior by acetylating myosin light chain kinase[J].PLoS One,2009,4(10):e7451.
[21]Lee CF,Ou DS,Lee SB,et al.hNaa10p contributes to tumorigenesis by facilitating DNMT1-mediated tumor[J].J Clin Invest,2013,120(8):2920-30.
[22]Botrugno OA,Paris S,Za L,et al.Characterization of the endogenous GIT1-betaPIX complex,and identification of its association to membranes[J].Eur J Cell Biol,2006,85(1):35-46.
[23]Frank SR,Hansen SH.The PIX-GIT complex:a G protein signaling cassette in control of cell shape[J].Semin Cell Dev Biol,2008,19(3):234-44.
[24]Hua KT,Tan CT,Johansson G,et al.N-alpha-acetyltransferase 10protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity[J].Cancer Cell,2011,19(2):218-31.
[25]Qian X,Li X,Lu Z.Protein kinase activity of the glycolytic enzyme PGK1 regulates autophagy to promote tumorigenesis[J].Autophagy,2017,13(7):1246-7.
[26]Oh JH,Hyuna JY,Varshavskya A.Control of Hsp90 chaperone and its clients by N-terminal acetylation and the N-end rule pathway[J].Proc Natl Acad Sci U S A,2017,114(22):E4370-9.
[27]Shim JH,Chung YH,Kim JA,et al.Clinical implications of arrest-defective protein 1 expression in hepatocellular carcinoma:a novel predictor of microvascular invasion[J].Dig Dis,2012,30(6):603-8.
[28]Ren T,Jiang B,Jin G,et al.Generation of novel monoclonal antibodies and their application for detecting ARD1 expression in colorectal cancer[J].Cancer Lett,2008,264(1):83-92.
[29]Jiang B,Ren T,Dong B,et al.Peptide mimic isolated by autoantibody reveals human arrest defective 1 overexpression is associated with poor prognosis for colon cancer patients[J].Am JPathol,2010,77(3):1095-103.
[30]Yang H,Li Q,Niu J,et al.micro RNA-342-5p and mi R-608 inhibit colon cancer tumorigenesis by targeting NAA10[J].Oncotarget,2016,7(3):2709-20.
[31]Zeng Y,Min L,Han Y,et al.Inhibition of STAT5a by Naa10p contributes to decreased breast cancer metastasis[J].Carcinogenesis,2014,35(10):2244-53.
[32]Min L,Ma RL,Yuan H,et al.Combined Expression of Metastasis Related Markers Naa10p,SNCG and PRL-3 and its Prognostic Value in Breast Cancer Patients[J].Asian Pac J Cancer Prev,2015,16(7):2819-26.
[33]Zeng Y,Liu C,Dong B,et al.Inverse correlation between Naa10p and MMP-9 expression and the combined prognostic value in breast cancer patients[J].Med Oncol,2013,30(2):562.
[34]Wang ZH,Gong JL,Yu M,et al.Up-regulation of human arrestdefective 1 protein is correlated with metastatic phenotype and poor prognosis in breast cancer[J].Asian Pac J Cancer Prev,2011,12(8):1973-7.
[35]Wang Z,Wang Z,Guo J,et al.Inactivation of androgen-induced regulator ARD1 inhibits androgen receptor acetylation and prostate tumorigenesis[J].Proc Natl Acad Sci U S A,2012,109(8):3053-8.
[36]Chen X,Yang C,Xie S,et al.Long non-coding RNA GAS5 and ZFAS1 are prognostic markers involved in translation targeted by miR-940 in prostate cancer[J].Oncotarget,2018,9(1):1048-62.
[37]Zeng Y,Zheng J,Zhao J,et al.High expression of Naa10p associates with lymph node metastasis and predicts favorable prognosis of oral squamous cell carcinoma[J].Tumour Biol,2016,37(5):6719-28.
[38]Arnesen T,Gromyko D,Horvli O,et al.Expression of N-Acetyl Transferase Human and Human Arrest Defective 1 Proteins in Thyroid Neoplasms[J].Thyroid,2005,15(10):1131-6.