UBE2C在结直肠癌中的研究现状与进展
|
摘要
世界范围内,结直肠癌(colorectal cancer,CRC)的发病率在恶性肿瘤中排名第三,其死亡率位居第四。近年来,随着人们生活水平的提高和生活方式及饮食结构的改变,CRC的发病率及死亡率呈上升趋势。尽管CRC早期诊断有所改善,但转移性CRC患者的总体5年生存率仍然很低。泛素蛋白酶体系统(ubiquitin proteasome system,UPS)是细胞质和细胞核内的一种依赖ATP的蛋白质降解途径。它通过泛素化-蛋白酶体-去泛素化机制调节其降解的蛋白质以维持体内的稳态。当调节的蛋白质失去稳定性时,会诱发癌症等疾病。泛素偶联酶(UBE2C)又名泛素结合酶10(UBH10),它在UPS中具有重要的生物学作用,是细胞周期进展和周期蛋白降解所必需的。UBE2C在CRC患者组织中高度表达,并且与肿瘤细胞的增殖、凋亡、侵袭性、预后和放化疗敏感性相关。目前已经证实UBE2C可作为CRC诊断、预后、淋巴结转移的潜在肿瘤标志物及CRC基因治疗的新靶点。本文就近年来关于UBE2C在CRC中的研究进展加以综述。
In the world,the incidence of colorectal cancer( CRC) is third in the malignant tumor,and the mortality rate is fourth. In recent years,with the improvement of people's living standards and changes in lifestyle and dietary structure,the incidence of CRC and mortality have been on the rise. The ubiquitin proteasome system( UPS) is an ATP-dependent protein degradation pathway in the cytoplasm and nucleus. It regulates its degraded proteins through ubiquitination-proteasome-deubiquitination mechanisms to maintain homeostasis. When the regulated protein loses its stability,it causes cancer and other diseases. Ubiquitin conjugating enzyme( UBE2C),also known as ubiquitin binding enzyme 10( UBH10),plays an important biological role in UPS,and is necessary for cell cycle progression and cyclin degradation. UBE2 C is highly expressed in the tissues of patients with colorectal cancer and is associated with the proliferation,apoptosis,invasiveness,prognosis and chemosensitivity of tumor cells. It has been confirmed that UBE2 C can be used as a potential tumor marker for colorectal cancer diagnosis,prognosis,lymph node metastasis and a new target for colorectal cancer gene therapy. This article reviews the progress of UBE2 C in colorectal cancer in recent years.
In the world,the incidence of colorectal cancer( CRC) is third in the malignant tumor,and the mortality rate is fourth. In recent years,with the improvement of people's living standards and changes in lifestyle and dietary structure,the incidence of CRC and mortality have been on the rise. The ubiquitin proteasome system( UPS) is an ATP-dependent protein degradation pathway in the cytoplasm and nucleus. It regulates its degraded proteins through ubiquitination-proteasome-deubiquitination mechanisms to maintain homeostasis. When the regulated protein loses its stability,it causes cancer and other diseases. Ubiquitin conjugating enzyme( UBE2C),also known as ubiquitin binding enzyme 10( UBH10),plays an important biological role in UPS,and is necessary for cell cycle progression and cyclin degradation. UBE2 C is highly expressed in the tissues of patients with colorectal cancer and is associated with the proliferation,apoptosis,invasiveness,prognosis and chemosensitivity of tumor cells. It has been confirmed that UBE2 C can be used as a potential tumor marker for colorectal cancer diagnosis,prognosis,lymph node metastasis and a new target for colorectal cancer gene therapy. This article reviews the progress of UBE2 C in colorectal cancer in recent years.
引文
[1]Jemal A,Bray F,Center MM,et al.Global cancer statistics[J].Ca A Cancer Journal for Clinicians,2015,65(2):87-108.
[2]Lan MG,Qing HT,Wang LS.Expressions of microRNA-101 and cyclooxygenase-2 in colorectal cancer[J].The Journal of Practical Medicine,2016,32(5):739-742.[赖明广,青海涛,王立生.microRNA-101和COX-2在结肠癌中的表达及其临床意义[J].实用医学杂志,2016,32(5):739-742.]
[3]Chen W,Zheng R,Baade PD,et al.Cancer statistics in China,2015[J].Ca A Cancer Journal for Clinicians,2016,66(2):115.
[4]Jiang CX,Shen YZ,Zhang ZH,et al.Analysis of incidence and survival rate of cancer among residents in Haining city from 2003 to2015[J].China Cancer,2018,27(4):267-272.[姜春晓,沈永洲,张志浩,等.2003-2015年浙江省海宁市居民癌症发病率及生存率分析[J].中国肿瘤,2018,27(4):267-272.]
[5]Chen D,Dou QP.The ubiquitin-proteasome system as a prospective molecular target for cancer treatment and prevention[J].Current Protein&Peptide Science,2010,11(6):459.
[6]Bennett EJ,Harper JW.DNA damage:Ubiquitin marks the spot[J].Nature Structural&Molecular Biology,2008,15(1):20.
[7]Goldknopf IL,Busch H.Isopeptide linkage between nonhistone and histone 2A polypeptides of chromosomal conjugate-protein A24[J].Proceedings of the National Academy of Sciences of the United States of America,1977,74(3):864-868.
[8]Nalepa G,Rolfe M,Harper JW.Drug discovery in the ubiquitinproteasome system[J].Nature Reviews Drug Discovery,2006,5(7):596.
[9]Wang SB,Wang F.Ubiquitin-conjugating enzyme E2C and tumors[J].Journal of Medical Postgraduates,2015,28(5):543-548.[王少冰,王芳.泛素结合酶E2C与肿瘤的关系研究进展[J].医学研究生学报,2015,28(5):543-548.]
[10]Han SS,Sun H,Liu QG.Research advances in UbcH10 and its relationship with cancer[J].Chinese Journal of Clinical Oncology,2011,38(14):867-869.[韩少山,孙昊,刘青光.Ubc H10与肿瘤关系研究进展[J].中国肿瘤临床,2011,38(14):867-869.]
[11]Wang R,Song Y,Liu X,et al.UBE2C induces EMT through Wnt/β-catenin and PI3K/Akt signaling pathways by regulating phosphorylation levels of Aurora-A[J].International Journal of Oncology,2017,50(4):1116.
[12]Ree JHV,Jeganathan KB,Malureanu L,et al.Overexpression of the E2 ubiquitin-conjugating enzyme UbcH10 causes chromosome missegregation and tumor formation[J].Journal of Cell Biology,2010,188(1):83.
[13]Chang L,Zhang Z,Yang J,et al.Molecular architecture and mechanism of the anaphase-promoting complex[J].Nature,2014,513(7518):388-393.
[14]Summers MK,Pan B,Mukhyala K,et al.The unique n-terminus of the UbcH10 E2 enzyme controls the threshold for APC activation and enhances checkpoint regulation of the APC[J].Molecular Cell,2008,31(4):544-556.
[15]Fujita T,Ikeda H,Taira N,et al.Overexpression of UbcH10 alternates the cell cycle profile and accelerate the tumor proliferation in colon cancer[J].Bmc Cancer,2009,9(1):87.
[16]Hanahan D,Weinberg RA.Hallmarks of cancer:The next generation[J].Cell,2011,144(5):646.
[17]Okamoto Y,Ozaki T,Miyazaki K,et al.UbcH10 is the cancerrelated E2 ubiquitin-conjugating enzyme[J].Cancer Research,2003,63(14):4167-4173.
[18]Hao Z,Zhang H,Cowell J.Ubiquitin-conjugating enzyme UBE2C:Molecular biology,role in tumorigenesis,and potential as a biomarker[J].Tumor Biology,2012,33(3):723-730.
[19]Rui W,Yue S,Xi L,et al.UBE2C induces EMT through Wnt/β-catenin and PI3K/Akt signaling pathways by regulating phosphorylation levels of Aurora-A[J].International Journal of Oncology,2017,50(4):1116-1126.
[20]Chen S,Chen Y,Hu C,et al.Association of clinicopathological features with UbcH10 expression in colorectal cancer[J].J Cancer Res Clin Oncol,2010,136(3):419-426.
[21]Chen SM,Chen YJ,Hu CJ.Lymph node metastasis of colorectal cancer and expression of UbcH10[J].Laboratory Medicine&Clinic,2015,12(20):3035-3037.[陈世敏,陈英剑,胡成进.结直肠癌淋巴结转移与泛素结合酶UbcH10的表达[J].检验医学与临床,2015,12(20):3035-3037.]
[22]Zhang Y,Tian S,Li X,et al.UBE2C promotes rectal carcinoma via miR-381[J].Cancer Biology&Therapy,2018,19(3):230-238.
[23]Zhang HQ,Zhao G,Ke B,et al.Overexpression of UBE2C correlates with poor prognosis in gastric cancer patients[J].Eur Rev Med Pharmacol Sci,2018,22(6):1665-1671.
[24]Pellino G,Pallante P,Malapelle U,et al.UbcH10 overexpression is less pronounced in older colorectal cancer patients[J].International Journal of Colorectal Disease,2016,31(7):1-2.
[25]Takahashi Y,Ishii Y,Nishida Y,et al.Detection of aberrations of ubiquitin-conjugating enzyme E2C gene(UBE2C)in advanced colon cancer with liver metastases by DNA microarray and twocolor FISH[J].Cancer Genetics&Cytogenetics,2006,168(1):30-35.
[26]Takayama T,Miyanishi K,Hayashi T,et al.Colorectal cancer:Genetics of development and metastasis[J].Journal of Gastroenterology,2006,41(3):185-192.
[27]Shankaran V,Wisinski KB,Mulcahy MF.The role of molecular markers in predicting response to therapy in patients with colorectal cancer[J].Molecular Diagnosis&Therapy,2008,12(2):87-98.
[28]Chen D,Dou QP.The ubiquitin-proteasome system as a prospective molecular target for cancer treatment and prevention[J].Current Protein&Peptide Science,2010,11(6):459.
[29]Chen SS,Wang QD,Wu JY,et al.Inhibitory effect of UbcH10gene silencing on colorectal cancer cell xenografts[J].Chinese Journal of Public Health,2012,28(9):1197-1199.[陈世敏,王启栋,吴建英,等.UbcH10基因沉默对裸鼠移植性大肠癌抑制作用[J].中国公共卫生,2012,28(9):1197-1199.]
[30]Bavi P,Uddin S,Ahmed M,et al.Bortezomib stabilizes mitotic cyclins and prevents cell cycle progression via inhibition of UBE2Cin colorectal carcinoma[J].American Journal of Pathology,2011,178(5):2109-2120.
[31]Li SZ,Song Y,Zhang HH,et al.UbcH10 overexpression increases carcinogenesis and blocks ALLN susceptibility in colorectal cancer[J].Sci Rep,2014,4(4):6910.
[32]Cacciola NA,Calabrese C,Malapelle U,et al.UbcH10 expression can predict prognosis and sensitivity to the antineoplastic treatment for colorectal cancer patients[J].Molecular Carcinogenesis,2016,55(5):793-807.
[2]Lan MG,Qing HT,Wang LS.Expressions of microRNA-101 and cyclooxygenase-2 in colorectal cancer[J].The Journal of Practical Medicine,2016,32(5):739-742.[赖明广,青海涛,王立生.microRNA-101和COX-2在结肠癌中的表达及其临床意义[J].实用医学杂志,2016,32(5):739-742.]
[3]Chen W,Zheng R,Baade PD,et al.Cancer statistics in China,2015[J].Ca A Cancer Journal for Clinicians,2016,66(2):115.
[4]Jiang CX,Shen YZ,Zhang ZH,et al.Analysis of incidence and survival rate of cancer among residents in Haining city from 2003 to2015[J].China Cancer,2018,27(4):267-272.[姜春晓,沈永洲,张志浩,等.2003-2015年浙江省海宁市居民癌症发病率及生存率分析[J].中国肿瘤,2018,27(4):267-272.]
[5]Chen D,Dou QP.The ubiquitin-proteasome system as a prospective molecular target for cancer treatment and prevention[J].Current Protein&Peptide Science,2010,11(6):459.
[6]Bennett EJ,Harper JW.DNA damage:Ubiquitin marks the spot[J].Nature Structural&Molecular Biology,2008,15(1):20.
[7]Goldknopf IL,Busch H.Isopeptide linkage between nonhistone and histone 2A polypeptides of chromosomal conjugate-protein A24[J].Proceedings of the National Academy of Sciences of the United States of America,1977,74(3):864-868.
[8]Nalepa G,Rolfe M,Harper JW.Drug discovery in the ubiquitinproteasome system[J].Nature Reviews Drug Discovery,2006,5(7):596.
[9]Wang SB,Wang F.Ubiquitin-conjugating enzyme E2C and tumors[J].Journal of Medical Postgraduates,2015,28(5):543-548.[王少冰,王芳.泛素结合酶E2C与肿瘤的关系研究进展[J].医学研究生学报,2015,28(5):543-548.]
[10]Han SS,Sun H,Liu QG.Research advances in UbcH10 and its relationship with cancer[J].Chinese Journal of Clinical Oncology,2011,38(14):867-869.[韩少山,孙昊,刘青光.Ubc H10与肿瘤关系研究进展[J].中国肿瘤临床,2011,38(14):867-869.]
[11]Wang R,Song Y,Liu X,et al.UBE2C induces EMT through Wnt/β-catenin and PI3K/Akt signaling pathways by regulating phosphorylation levels of Aurora-A[J].International Journal of Oncology,2017,50(4):1116.
[12]Ree JHV,Jeganathan KB,Malureanu L,et al.Overexpression of the E2 ubiquitin-conjugating enzyme UbcH10 causes chromosome missegregation and tumor formation[J].Journal of Cell Biology,2010,188(1):83.
[13]Chang L,Zhang Z,Yang J,et al.Molecular architecture and mechanism of the anaphase-promoting complex[J].Nature,2014,513(7518):388-393.
[14]Summers MK,Pan B,Mukhyala K,et al.The unique n-terminus of the UbcH10 E2 enzyme controls the threshold for APC activation and enhances checkpoint regulation of the APC[J].Molecular Cell,2008,31(4):544-556.
[15]Fujita T,Ikeda H,Taira N,et al.Overexpression of UbcH10 alternates the cell cycle profile and accelerate the tumor proliferation in colon cancer[J].Bmc Cancer,2009,9(1):87.
[16]Hanahan D,Weinberg RA.Hallmarks of cancer:The next generation[J].Cell,2011,144(5):646.
[17]Okamoto Y,Ozaki T,Miyazaki K,et al.UbcH10 is the cancerrelated E2 ubiquitin-conjugating enzyme[J].Cancer Research,2003,63(14):4167-4173.
[18]Hao Z,Zhang H,Cowell J.Ubiquitin-conjugating enzyme UBE2C:Molecular biology,role in tumorigenesis,and potential as a biomarker[J].Tumor Biology,2012,33(3):723-730.
[19]Rui W,Yue S,Xi L,et al.UBE2C induces EMT through Wnt/β-catenin and PI3K/Akt signaling pathways by regulating phosphorylation levels of Aurora-A[J].International Journal of Oncology,2017,50(4):1116-1126.
[20]Chen S,Chen Y,Hu C,et al.Association of clinicopathological features with UbcH10 expression in colorectal cancer[J].J Cancer Res Clin Oncol,2010,136(3):419-426.
[21]Chen SM,Chen YJ,Hu CJ.Lymph node metastasis of colorectal cancer and expression of UbcH10[J].Laboratory Medicine&Clinic,2015,12(20):3035-3037.[陈世敏,陈英剑,胡成进.结直肠癌淋巴结转移与泛素结合酶UbcH10的表达[J].检验医学与临床,2015,12(20):3035-3037.]
[22]Zhang Y,Tian S,Li X,et al.UBE2C promotes rectal carcinoma via miR-381[J].Cancer Biology&Therapy,2018,19(3):230-238.
[23]Zhang HQ,Zhao G,Ke B,et al.Overexpression of UBE2C correlates with poor prognosis in gastric cancer patients[J].Eur Rev Med Pharmacol Sci,2018,22(6):1665-1671.
[24]Pellino G,Pallante P,Malapelle U,et al.UbcH10 overexpression is less pronounced in older colorectal cancer patients[J].International Journal of Colorectal Disease,2016,31(7):1-2.
[25]Takahashi Y,Ishii Y,Nishida Y,et al.Detection of aberrations of ubiquitin-conjugating enzyme E2C gene(UBE2C)in advanced colon cancer with liver metastases by DNA microarray and twocolor FISH[J].Cancer Genetics&Cytogenetics,2006,168(1):30-35.
[26]Takayama T,Miyanishi K,Hayashi T,et al.Colorectal cancer:Genetics of development and metastasis[J].Journal of Gastroenterology,2006,41(3):185-192.
[27]Shankaran V,Wisinski KB,Mulcahy MF.The role of molecular markers in predicting response to therapy in patients with colorectal cancer[J].Molecular Diagnosis&Therapy,2008,12(2):87-98.
[28]Chen D,Dou QP.The ubiquitin-proteasome system as a prospective molecular target for cancer treatment and prevention[J].Current Protein&Peptide Science,2010,11(6):459.
[29]Chen SS,Wang QD,Wu JY,et al.Inhibitory effect of UbcH10gene silencing on colorectal cancer cell xenografts[J].Chinese Journal of Public Health,2012,28(9):1197-1199.[陈世敏,王启栋,吴建英,等.UbcH10基因沉默对裸鼠移植性大肠癌抑制作用[J].中国公共卫生,2012,28(9):1197-1199.]
[30]Bavi P,Uddin S,Ahmed M,et al.Bortezomib stabilizes mitotic cyclins and prevents cell cycle progression via inhibition of UBE2Cin colorectal carcinoma[J].American Journal of Pathology,2011,178(5):2109-2120.
[31]Li SZ,Song Y,Zhang HH,et al.UbcH10 overexpression increases carcinogenesis and blocks ALLN susceptibility in colorectal cancer[J].Sci Rep,2014,4(4):6910.
[32]Cacciola NA,Calabrese C,Malapelle U,et al.UbcH10 expression can predict prognosis and sensitivity to the antineoplastic treatment for colorectal cancer patients[J].Molecular Carcinogenesis,2016,55(5):793-807.