SEPT9基因在肿瘤中的研究进展
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摘要
Septin 9(SEPT9)基因是保守骨架蛋白基因家族成员之一,具有三磷酸鸟苷酶活性(GTPase),可参与细胞极化、细胞分裂和细胞膜重构等多种生物过程。研究证实SEPT9与诸如恶性肿瘤等人类疾病发生发展密切相关,且SEPT9已成为现阶段肿瘤相关研究的新热点。本文阐述了SEPT9基因的结构特点、SEPT9蛋白作用机制及其在多种常见肿瘤发生进展中的作用,探讨了其作为标志物在肿瘤早期筛查中的潜在应用价值。
Septin 9(SEPT9)gene,a member of the conserved framework protein genes family,has guanosine triphosphataseg(GTPase)activity and play an important role in a wide range of biological processes such as cell division,cell polarization and membrane remodeling.Accumulated evidence have confirmed that SEPT9 is closely related to the generation and development of human diseases.And SEPT9 has become the new aroused general interest in tumor related research at this stage.This article mainly reviews the structural features of SEPT9 gene,action mechanism of SEPT9 protein and the role of SEPT9 gene in a variety of common oncogenesis,and explores the potential value of SEPT9 as a marker in early tumor screening.
Septin 9(SEPT9)gene,a member of the conserved framework protein genes family,has guanosine triphosphataseg(GTPase)activity and play an important role in a wide range of biological processes such as cell division,cell polarization and membrane remodeling.Accumulated evidence have confirmed that SEPT9 is closely related to the generation and development of human diseases.And SEPT9 has become the new aroused general interest in tumor related research at this stage.This article mainly reviews the structural features of SEPT9 gene,action mechanism of SEPT9 protein and the role of SEPT9 gene in a variety of common oncogenesis,and explores the potential value of SEPT9 as a marker in early tumor screening.
引文
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[4] HALL P A.The pathobiology of the septin gene family[J].Journal Pathol,2004,204(4):489-505.
[5]温蕾,冯义朝,杜夏,等.SEPT9基因甲基化在结直肠癌诊断中的研究进展[J].胃肠病学,2017(6):381-384.
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[8] GOLAN M.SEPT9is required for the association between HIF-1αand importin-αto promote efficient nuclear translocation[J].Cell Cycle,2013,12(14):2297-2308.
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[22]KAZANETS A,SHORSTOVA T,HILMI K,et al.Epigenetic silencing of tumor suppressor genes:Paradigms,puzzles and potential[J].Biochimica Et Biophysica Acta,2016,1865(2):275-288.
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[30]TOYOTA M,AHUJA N,OHE T M,et al.The influence of methylated septin9gene on RNA and protein level in coloretal cancel[J].Pathol Oncol Res,2011,17(3):503-509
[31]DEVOS T,TETZNER R,MODEL F,et al.Circulating methylated SEPT9 DNA in plasma is a biomarker for colorectal cancer[J].Clin Chem,2009,55(7):1337-1346.
[32]TANZER M,BALLUFF B,DISTLER J,et al.Performance of epigenetic markers SEPT9and ALX4in plasma for detection of colorectal precancerous lesions[J].PLos One,2010,5(2):9061.
[33]WARREN J D,WEI X,BUNKER A M,et al.Septin 9methylated DNA is a sensitive and specific blood test for colorectal cancer[J].BMC Medicine,2011,9(1):133.
[34]TTH K,SIPOS F,KALMR A,et al.Detection of methylated SEPT9in plasma is a reliable screening method for both left-and right-sided colon cancers[J].PLos One,2012,7(9);46.
[35]CHURCH T R,WANDELL M,LOFTON-DAY C,et al.Prospective evaluation of methylated SEPT9in plasma for detection of asymptomatic colorectal cancer[J].Gut,2014,63(2):317-325.
[36]CHEN W D,HAN Z J,SKOLETSKY J,et al.Detection in fecal DNA of colon cancer-specific methylation of the nonexpressed vimentin gene[J].J Nat Cancer Institute,2005,97(15):1124-1132.
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[38]GRTZMANN R,MOLNAR B,PILARSKY C,et al.Sensitive detection of colorectal cancer in peripheral blood by septin 9DNA methylation assay[J].PLos One,2008,3(11):3759.
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[40]MONTAGNA C,LYU M S,HUNTEr K,et al.The Septin 9(MSF)gene is amplified and overexpressed in mouse mammary gland adenocarcinomas and human breast cancer cell lines[J].Cancer Res,2003,63(9):2179.
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[42]CONNOLLY D,YANG Z,CASTALDI M,et al.Septin 9isoform expression,localization and epigenetic changes during human and mouse breast cancer progression[J].Breast Cancer Res,2011,13(4):76.
[43]SCOTT M,MCCLUGGAGE W G,HILLAN K J,et al.Altered patterns of transcription of the septin gene,SEPT9,in ovarian tumorigenesis[J].Int J cancer,2006,118(5):1325-1329.
[44]吕讷男,韩超,徐晓红,等.卵巢上皮性癌组织及外周血中septin-9的表达情况[J].北京医学,2015,37(7):662-666.
[45]吕讷男,姚洪文,肖汀,等.卵巢上皮性癌患者外周血中septin-9和clusterin蛋白的表达及其意义[J].中华妇产科杂志,2015,50(9):679-684.
[46]CERVEIRA N,BIZARRO S,TEIXEIRA M R.MLLSEPTIN gene fusions in hematological malignancies[J].Bio Chem,2011,392(8-9):713-724.
[47]ONO R,TAKI T,TAKETANI T,et al.SEPTIN6,a human homologue to mouse Septin6,is fused to MLL in infant acute myeloid leukemia with complex chromosomal abnormalities involving 11q23and Xq24.[J].Cancer Res,2002,62(2):333-337.
[48]OSAKA M,ROWLEY J D,ZELEZNIK-LE N J.MSF(MLL septin-link fusion),a fusion partner gene of MLL,in a therapy-related acute myeloid leukemia with a t(11;17)(q23:q25)[J].Pro Nat Aca Sci USA,1999,96(11):6428.
[49]KOJIMA K,SAKAI I,HASEGAWA A,et al.FIJ10849,a septin family gene,fuses MLL in a novel leukemia cell line CNLBC1derived from chronic neutrophilic leukemia in transformation with t(4;11)(q21;q23).[J].Leukemia,2004,18(5):998-1005.
[50] TAKI T,OHNISHI H,SHINOHARA K,et al.AF17q25,aputative septin family gene,fuses the MLL gene in acute myeloid leukemia with t(11;17)(q23;q25)[J].Cancer Research,1999,59(17):4261-5.
[51]KUROSU T,TSUJI K,OHKI M,et al.A variant-type MLL/SEPT9,fusion transcript in adult de novo acute monocytic leukemia(M5b)with t(11;17)(q23;q25)[J].Int J Hema,2008,88(2):192.
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[2]余智操,吴晋,张琼,等.SEPT9基因与恶性肿瘤关系的研究进展[J].现代肿瘤医学,2018(2):297-301.
[3] MCILHATTON M A,BURROWS J F,DONAGHY P G,et al.Genomic organization,complex splicing pattern and expression of a human septin gene on chromosome17q25.3[J].Oncogene,2001,20(41):5930-5939.
[4] HALL P A.The pathobiology of the septin gene family[J].Journal Pathol,2004,204(4):489-505.
[5]温蕾,冯义朝,杜夏,等.SEPT9基因甲基化在结直肠癌诊断中的研究进展[J].胃肠病学,2017(6):381-384.
[6]吕炳建,来茂徳.Septin基因家族与人类疾病[J].国际遗传学杂志,2006,29(6):441-445.
[7] SELLIN M E,STENMARK S,GULLBERG M.Mammalian SEPT9isoforms direct microtubule-dependent arrangements of septin core heteromers[J].Mol Bio Cell,2012,23(21):4242.
[8] GOLAN M.SEPT9is required for the association between HIF-1αand importin-αto promote efficient nuclear translocation[J].Cell Cycle,2013,12(14):2297-2308.
[9] SMITH C,DOLAT L,ANGELIS D,et al.Septin 9Exhibits Polymorphic Binding to F-Actin and Inhibits Myosin and Cofilin Activity.[J].J Mol Bio,2015,427(20):3273-3284.
[10]RATH N,OLSON M F.Rho-associated kinases in tumorigenesis;re-considering ROCK inhibition for cancer therapy[J].Embo Reports,2012,13(10):900-908.
[11]林春燕,税青林.SEPT9与恶性肿瘤的研究进展[J].泸州医学院学报,2013,36(2):186-188.
[12]YEH Y T,HUR S S,CHANG J,et al.Matrix stiffness regulates endothelial cell proliferation through septin 9[J].PLoS One,2012,7(10):46889.
[13]MINGOSION A M,MARIETTA P M,KOLLER E,et al.Inhibition of JNK reduces G2/M transit independent of p53,leading to endoreduplication,decreased proliferation,and apoptosis in breast cancer cells[J].Oncogene,2004,23(2):596-604.
[14]GONZALEZ M E,MAKAROVA O,PETERSON E A,et al.Up-regulation of SEPT9_v1stabilizes c-Jun-N-Terminal kinase and contributes to its pro-proliferative activity in mammary epithelial cells[J].Cellular Signalling,2009,21(4):477-487.
[15]BRDOS J I,ASHCROFT.Hypoxia-inducible factor-1and oncogenic signaling[J].Bioessays News Dev Bio,2004,26(3):262-269.
[16]RANKIN E B,GIACCIA A J.Hypoxic control of metastasis[J].Science,2016,352(6282):175-180.
[17]刘文,狄建忠,邹扬,等.SEPT 9基因与恶性肿瘤关系的研究进展[J].肿瘤,2010,30(9):798-801.
[18]马强.人类SEPT9蛋白致病机制的研究进展[J].医学美学美容,2015,24(4):769-770.
[19]AMIR S,WANG R,MATZKIN H,et al.MSF-A interacts with hypoxia-inducible factor-1alpha and augments hypoxia-inducible factor transcriptional activation to affect tumorigenicity and angiogenesis.[J].Cancer Res,2006,66(2):856.
[20]PETERSON E A,STANBERY L,LI C,et al,SEPT9_i1and genomic instability:Mechanistic insights and relevance to tumorigenesis[J].Genes Chromosomes Cancer,2011,50(11):940-949.
[21]FCHTBAUER A,LASSEN L B,JENSEN A B,et al.Septin9is involved in septin filament formation and cellular stability[J].Bio Chem,2011,392(9):769.
[22]KAZANETS A,SHORSTOVA T,HILMI K,et al.Epigenetic silencing of tumor suppressor genes:Paradigms,puzzles and potential[J].Biochimica Et Biophysica Acta,2016,1865(2):275-288.
[23]蔡克银,徐梅华,王晓.粪便DNA中联合SFRP1及SEPT9基因甲基化检测对老年性结直肠癌早期诊断的临床研究[J].临床肿瘤学杂志,2018,24(1):25-29.
[24]XIAOJING YANG,FIDES LAY,HAN HAN,et al.Targeting DNA methylation for epigenetic therapy[J].Tre Pharm Sci,2010,31(11):536-546.
[25]张玲,盛树力,秦川.表观遗传学药物的研究进展[J].中国药理学通报,2013,29(3):297-303.
[26]JONES P A,BAYLIN S B.The epigenomics of cancer[J].Cell,2007,128(4):683-692.
[27]AHMED D,DANIELSEN S A,AAGESEN T H,et al.A tissue-based comparative effectiveness analysis of biomarkers for early detection of colorectal tumors[J].Clin Trans Gas,2012,3(12):27.
[28]SCHRCK A,LEISSE A,DE V L,et al.Free-circulating methylated DNA in blood for diagnosis,staging,prognosis,and monitoring of head and neck squamous cell carcinoma patients:an observational prospective cohort study[J].Clin Chem,2017,63(7):1288.
[29]NAGATA K,KAWAJIRI A,MATSUI S,et al.Filament formation of MSF-A,a mammalian septin,in human mammary epithelial cells depends on interactions with microtubules.[J].J Bio Chem,2003,278(20):18538-18543.
[30]TOYOTA M,AHUJA N,OHE T M,et al.The influence of methylated septin9gene on RNA and protein level in coloretal cancel[J].Pathol Oncol Res,2011,17(3):503-509
[31]DEVOS T,TETZNER R,MODEL F,et al.Circulating methylated SEPT9 DNA in plasma is a biomarker for colorectal cancer[J].Clin Chem,2009,55(7):1337-1346.
[32]TANZER M,BALLUFF B,DISTLER J,et al.Performance of epigenetic markers SEPT9and ALX4in plasma for detection of colorectal precancerous lesions[J].PLos One,2010,5(2):9061.
[33]WARREN J D,WEI X,BUNKER A M,et al.Septin 9methylated DNA is a sensitive and specific blood test for colorectal cancer[J].BMC Medicine,2011,9(1):133.
[34]TTH K,SIPOS F,KALMR A,et al.Detection of methylated SEPT9in plasma is a reliable screening method for both left-and right-sided colon cancers[J].PLos One,2012,7(9);46.
[35]CHURCH T R,WANDELL M,LOFTON-DAY C,et al.Prospective evaluation of methylated SEPT9in plasma for detection of asymptomatic colorectal cancer[J].Gut,2014,63(2):317-325.
[36]CHEN W D,HAN Z J,SKOLETSKY J,et al.Detection in fecal DNA of colon cancer-specific methylation of the nonexpressed vimentin gene[J].J Nat Cancer Institute,2005,97(15):1124-1132.
[37]LOFTONDAY C,MODEL F,DEVOS T,et al.DNA methylation biomarkers for blood-based colorectal cancer screening[J].Clin Chem,2008,54(2):414.
[38]GRTZMANN R,MOLNAR B,PILARSKY C,et al.Sensitive detection of colorectal cancer in peripheral blood by septin 9DNA methylation assay[J].PLos One,2008,3(11):3759.
[39]XUE M,LAI S C,WANG L J.Non-invasive DNA methylation biomarkers in colorectal cancer:A systematic review[J].J Dig Dis,2016,16(12):699-712.
[40]MONTAGNA C,LYU M S,HUNTEr K,et al.The Septin 9(MSF)gene is amplified and overexpressed in mouse mammary gland adenocarcinomas and human breast cancer cell lines[J].Cancer Res,2003,63(9):2179.
[41]GONZALEZ M E,PETERSON E A,Privette L M,et al.High SEPT9_V1expression in human breast cancer cells is associated with oncogenic phenotypes.[J].Cancer Res,2007,67(18):8554-8564.
[42]CONNOLLY D,YANG Z,CASTALDI M,et al.Septin 9isoform expression,localization and epigenetic changes during human and mouse breast cancer progression[J].Breast Cancer Res,2011,13(4):76.
[43]SCOTT M,MCCLUGGAGE W G,HILLAN K J,et al.Altered patterns of transcription of the septin gene,SEPT9,in ovarian tumorigenesis[J].Int J cancer,2006,118(5):1325-1329.
[44]吕讷男,韩超,徐晓红,等.卵巢上皮性癌组织及外周血中septin-9的表达情况[J].北京医学,2015,37(7):662-666.
[45]吕讷男,姚洪文,肖汀,等.卵巢上皮性癌患者外周血中septin-9和clusterin蛋白的表达及其意义[J].中华妇产科杂志,2015,50(9):679-684.
[46]CERVEIRA N,BIZARRO S,TEIXEIRA M R.MLLSEPTIN gene fusions in hematological malignancies[J].Bio Chem,2011,392(8-9):713-724.
[47]ONO R,TAKI T,TAKETANI T,et al.SEPTIN6,a human homologue to mouse Septin6,is fused to MLL in infant acute myeloid leukemia with complex chromosomal abnormalities involving 11q23and Xq24.[J].Cancer Res,2002,62(2):333-337.
[48]OSAKA M,ROWLEY J D,ZELEZNIK-LE N J.MSF(MLL septin-link fusion),a fusion partner gene of MLL,in a therapy-related acute myeloid leukemia with a t(11;17)(q23:q25)[J].Pro Nat Aca Sci USA,1999,96(11):6428.
[49]KOJIMA K,SAKAI I,HASEGAWA A,et al.FIJ10849,a septin family gene,fuses MLL in a novel leukemia cell line CNLBC1derived from chronic neutrophilic leukemia in transformation with t(4;11)(q21;q23).[J].Leukemia,2004,18(5):998-1005.
[50] TAKI T,OHNISHI H,SHINOHARA K,et al.AF17q25,aputative septin family gene,fuses the MLL gene in acute myeloid leukemia with t(11;17)(q23;q25)[J].Cancer Research,1999,59(17):4261-5.
[51]KUROSU T,TSUJI K,OHKI M,et al.A variant-type MLL/SEPT9,fusion transcript in adult de novo acute monocytic leukemia(M5b)with t(11;17)(q23;q25)[J].Int J Hema,2008,88(2):192.
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