甲基转移酶3在前列腺癌中的表达及其临床意义
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摘要
目的探讨甲基转移酶3(METTL3)在前列腺癌组织中的表达及其临床意义。方法通过对TCGA数据集资料分析并运用蛋白印迹(Western blot)、免疫组化学技术(IHC),研究METTL3 mRNA和蛋白在前列腺癌和癌旁组织中的表达差异,并分析其在癌组织中的表达水平与临床病理资料的相关性。结果 METTL3 mRNA和蛋白在前列腺癌中的表达均明显高于癌旁良性组织,差异具有统计学意义(均P<0.01);METTL3蛋白表达主要定位在前列腺的细胞核,胞质中少量表达;在前列腺癌中,METTL3 mRNA的表达水平与Gleason评分呈正相关关系(r=0.195,P <0.01),METTL3蛋白的表达水平与PSA值、Gleason评分均呈正相关(r=0.381,P <0.05;r=0.449,P <0.01)。结论 METTL3与前列腺癌的发生、发展及分化密切相关,并可能与PSA联合作为前列腺癌的诊断标记物。
Objective To investigate the expression and clinical significance of METTL3 in prostate cancer.MethodsTCGA datasets,Western blot and immunohistochemistry(IHC)were used to study the expression ofMETTL3 gene in prostate cancer and adjacent tissues,and the correlation between METTL3 expression in cancertissues and clinical data was analyzed.ResultsThe expression of METTL3 at mRNA and protein level in prostatecancer were significantly higher than those in adjacent tissues. The difference was statistically significant(P < 0.01,respectively). The METTL3 protein was mainly expressed in the nuclei of the prostate and is slightly expressed inthe cytoplasm. In prostate cancer,the expression level of METTL3 mRNA was positively correlated with Gleasonscore(r = 0.195,P < 0.01)and the level of METTL3 protein was correlated with PSA value and Gleason score(r = 0.381,P < 0.05;r = 0.449,P < 0.01).ConclusionMETTL3 is closely related to the occurrence,developmentand differentiation of prostate cancer,and may be combined with PSA as a diagnostic marker for prostate cancer.
Objective To investigate the expression and clinical significance of METTL3 in prostate cancer.MethodsTCGA datasets,Western blot and immunohistochemistry(IHC)were used to study the expression ofMETTL3 gene in prostate cancer and adjacent tissues,and the correlation between METTL3 expression in cancertissues and clinical data was analyzed.ResultsThe expression of METTL3 at mRNA and protein level in prostatecancer were significantly higher than those in adjacent tissues. The difference was statistically significant(P < 0.01,respectively). The METTL3 protein was mainly expressed in the nuclei of the prostate and is slightly expressed inthe cytoplasm. In prostate cancer,the expression level of METTL3 mRNA was positively correlated with Gleasonscore(r = 0.195,P < 0.01)and the level of METTL3 protein was correlated with PSA value and Gleason score(r = 0.381,P < 0.05;r = 0.449,P < 0.01).ConclusionMETTL3 is closely related to the occurrence,developmentand differentiation of prostate cancer,and may be combined with PSA as a diagnostic marker for prostate cancer.
引文
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[2]SIEGEL R L,MILLER K D,JEMAL A.Cancer statistics,2018[J].CA Cancer J Clin,2018,68(1):7-30.
[3]韩苏军,张思维,陈万青,等.中国前列腺癌死亡现状及流行趋势分析[J].中华泌尿外科杂志,2012,33(11):836-839.
[4]MEYER K D,JAFFREY S R.The dynamic epitranscriptome:N6-methyladenosine and gene expression control[J].Nat Rev Mol Cell Biol,2014,15(5):313-326.
[5]DENG X,SU R,FENG X,et al.Role of N6-methyladenosine modification in cancer[J].Curr Opin Genet Dev,2018,48:1-7.
[6]DU M,ZHANG Y,MAO Y,et al.MiR-33a suppresses proliferation of NSCLC cells via targeting METTL3 mRNA[J].Biochem Biophys Res Commun,2017,482(4):582-589.
[7]CHEN M,WEI L,LAW C T,et al.RNA N6-methyladenosine methyltransferase-like 3 promotes liver cancer progression through YTHDF2-dependent posttranscriptional silencing of SOCS2[J].Hepatology,2018,67(6):2254-2270.
[8]BARBIERI I,TZELEPIS K,PANDOLFINI L,et al.Promoterbound METTL3 maintains myeloid leukaemia by m6A-dependent translation control[J].Nature,2017,552(7683):126-131.
[9]郑宇楠,李辉,苗劲柏,等.CTGF、TGF-131和13-Gal在原发性肺大疱组织的表达及相关性研究[J].中华心血管外科杂志,2017,33(4):222-225.
[10]丁奇,苗文隆,刘硕,等.合并前列腺炎症的良性前列腺增生组织中Integrinα2β1/CD133表达及其意义[J].中华男科学杂志,2011,17(10):909-912.
[11]BOKAR J A,SHAMBAUGH M E,POLAYES D,et al.Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA(N6-adenosine)-methyltransferase[J].RNA,1997,3(11):1233-1247.
[12]LEACH R A,TUCK M T.Expression of the mRNA(N6-adenosine)-methyltransferase S-adenosyl-L-methionine binding subunit mRNA in cultured cells[J].Int J Biochem Cell Biol,2001,33(10):984-99.
[13]LIU J,YUE Y,HAN D,et al.A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation[J].Nat Chem Biol,2014,10(2):93-95.
[14]PING X L,SUN B F,WANG L,et al.Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase[J].Cell Res,2014,24(2):177-189.
[15]BOCCALETTO P,MACHNICKA M A,PURTA E,et al.MODO-MICS:a database of RNA modification pathways.2017 update[J].Nucleic Acids Res,2018,46(D1):D303-D307.
[16]WEI C M,GERSHOWITZ A,MOSS B.Methylated nucleotides block 5′terminus of HeLa cell messenger RNA[J].Cell,1975,4(4):379-386.
[17]LIN S,CHOE J,DU P,et al.METTL3 promotes translation in human cancer cells[J].Mol Cell,2016,62(3):335-345.
[18]LUO G Z,MACQUEEN A,ZHENG G,et al.Unique features of the m6A methylome in Arabidopsis thaliana[J].Nat Commun,2014,5:5630.
[19]ROIGNANT J Y,SOLLER M.m6A in mRNA:an ancient mechanism for fine-tuning gene expression[J].Trends Genet,2017,33(6):380-390.
[20]CAI X,WANG X,CAO C,et al.HBXIP-elevated methyltransferase METTL3 promotes the progression of breast cancer via inhibiting tumor suppressor let-7g[J].Cancer Lett,2017,415:11-19.
[21]WANG X,LI Z,KONG B,et al.Reduced m6A mRNA methylation is correlated with the progression of human cervical cancer[J].Oncotarget,2017,8(58):98918-98930.
[22]LI X,TANG J,HUANG W,et al.The M6A methyltransferase METTL3:acting as a tumor suppressor in renal cell carcinoma[J].Oncotarget,2017,8(56):96103-96116.
[23]VU L P,PICKERING B F,CHENG Y,et al.The N6-methyladenosine(m6A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells[J].Nat Med,2017,23(11):1369-1376.
[24]XU K,YANG Y,FENG G H,et al.Mettl3-mediated m6A regulates spermatogonial differentiation and meiosis initiation[J]Cell Res,2017,27(9):1100-1114.
[25]LI H B,TONG J,ZHU S,et al.m6A mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways[J].Nature,2017,548(7667):338-342.
[26]TAKETO K,KONNO M,ASAI A,et al.The epitranscriptome m6A writer METTL3 promotes chemo-and radioresistance in pancreatic cancer cells[J].Int J Oncol,2018,52(2):621-629.