miR-146a与消化系统肿瘤的研究进展
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摘要
微小RNA(microRNA,miRNA)是一类非编码小分子RNA,长约21～25 nt,由基因组转录,负调控基因的表达,影响细胞增殖、分化、凋亡等重要生命活动。miR-146a是其中一种多功能miRNA,研究发现其在食管癌、胃癌、肝癌、胰腺癌、结肠癌等多种消化系统肿瘤中表达降低,通过调控靶基因的表达影响肿瘤的发生发展。本文就miR-146a在消化系统肿瘤中的研究现状作一简要综述。
MicroRNAs(miRNAs) are non-coding small RNAs of about 21 ～25 nucleotides in length, transcribed by genome, which regulate gene expression in post-transcriptional processing. microRNAs are involved in cell proliferation, differentiation and apoptosis regulation of important life activities. mi R-146 a is one of the multifunctional miRNAs that is down-regulated in esophageal cancer, gastric cancer, liver cancer, pancreatic cancer, colon cancer and other digestive system tumors. miR-146 a affects tumorigenesis by regulating the expression of target genes. This review summarizes the current status of miR-146 a in digestive system tumors.
MicroRNAs(miRNAs) are non-coding small RNAs of about 21 ～25 nucleotides in length, transcribed by genome, which regulate gene expression in post-transcriptional processing. microRNAs are involved in cell proliferation, differentiation and apoptosis regulation of important life activities. mi R-146 a is one of the multifunctional miRNAs that is down-regulated in esophageal cancer, gastric cancer, liver cancer, pancreatic cancer, colon cancer and other digestive system tumors. miR-146 a affects tumorigenesis by regulating the expression of target genes. This review summarizes the current status of miR-146 a in digestive system tumors.
引文
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[12]Qiu Z,Li H,Wang J,et al.miR-146a and miR-146b in the diagnosis and prognosis of papillary thyroid carcinoma[J].Oncol Rep,2017,38(5):2735-2740.
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[20]Layke John C.,Lopez Peter P.胃癌:诊断和治疗方案的选择[J].中国全科医学,2015(3):248-249.
[21]Kogo R,Mimori K,Tanaka F,et al.Clinical Significance of miR-146a in Gastric Cancer Cases[J].Clinical Cancer Research,2011,17(13):4277-4284.
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[24]张伟,周林,韩东升,等.miR-146a抑制胃癌细胞转移潜能机制探讨[J].中华肿瘤防治杂志,2015,22(19):1512-1517.
[25]Zhou L,Zhao X,Han Y,et al.Regulation of UHRF1 by miR-146a/b modulates gastric cancer invasion and metastasis.[J].Faseb Journal Official Publication of the Federation of American Societies for Experimental Biology,2013,27(12):4929-4939.
[26]Sha M,Ye J,Zhang L X,et al.Celastrol induces apoptosis of gastric cancer cells by miR-146a inhibition of NF-kappaBactivity[J].Cancer Cell Int,2013,13(1):50.
[27]Xiao B,Zhu E D,Li N,et al.Increased miR-146a in gastric cancer directly targets SMAD4 and is involved in modulating cell proliferation and apoptosis[J].Oncol Rep,2012,27(2):559-566.
[28]Crone S G,Jacobsen A,Federspiel B,et al.microRNA-146a inhibits G protein-coupled receptor-mediated activation of NF-κB by targeting CARD10 and COPS8 in gastric cancer[J].Molecular Cancer,2012,11(1):1-14.
[29]Rong M,He R,Dang Y,et al.Expression and clinicopathological significance of miR-146a in hepatocellular carcinoma tissues[J].Upsala Journal of Medical Sciences,2013,119(1):19-24.
[30]Zhang Z,Zhang Y,Sun X,et al.microRNA-146a inhibits cancer metastasis by downregulating VEGF through dual pathways in hepatocellular carcinoma[J].Molecular Cancer,2015,14(1):5.
[31]Huang S,He R,Rong M,et al.Synergistic effect of MiR-146a mimic and cetuximab on hepatocellular carcinoma cells.[J].Biomed Research International,2014,2014(6):384121.
[32]Li Y,VandenBoom T G,Wang Z,et al.miR-146a Suppresses Invasion of Pancreatic Cancer Cells[J].Cancer Research,2010,70(4):1486-1495.
[33]Ali S,Ahmad A,Aboukameel A,et al.Deregulation of miR-146a expression in a mouse model of pancreatic cancer affecting EGFR signaling[J].Cancer Lett,2014,351(1):134-142.
[34]RR A F A N.Diagnostic microRNA markers to screen for sporadic human colon cancer in stool:I.Proof of principle.[J].Cancer Genomics&Proteomics,2013,10(3):93-113.
[35]Sathyanarayanan A,Chandrasekaran K S,Karunagaran D.microRNA-146a inhibits proliferation,migration and invasion of human cervical and colorectal cancer cells[J].Biochem Biophys Res Commun,2016,480(4):528-533.
[36]Lu D,Yao Q,Zhan C,et al.MicroRNA-146a promote cell migration and invasion in human colorectal cancer via carboxypeptidase M/src-FAK pathway[J].Oncotarget,2017,8(14):22674-22684.
[37]Bleau A M,Redrado M,Nistal-Villan E,et al.miR-146a targets c-met and abolishes colorectal cancer liver metastasis[J].Cancer Lett,2018,414:257-267.
[38]Omrane I,Kourda N,Stambouli N,et al.MicroRNAs 146a and147 b Biomarkers for Colorectal Tumor’s Localization[J].BioMed Research International,2014,2014:1-9.
[39]Khorrami S,Zavaran H A,Mowla S J,et al.MicroRNA-146a induces immune suppression and drug-resistant colorectal cancer cells[J].Tumour Biol,2017,39(5):1393391299.
[40]Shastry B S.SNPs:impact on gene function and phenotype.[J].Methods in Molecular Biology,2009,578(578):3.
[41]Hu Y,Yu C Y,Wang J L,et al.MicroRNA sequence polymorphisms and the risk of different types of cancer[J].Scientific Reports,2014,4(4):3648.
[42]Guo H,Wang K,Xiong G,et al.A functional varient in microRNA-146a is associated with risk of esophageal squamous cell carcinoma in Chinese Han[J].Fam Cancer,2010,9(4):599-603.
[43]Xu Z,Zhang L,Cao H,et al.MiR-146a rs2910164 G/Cpolymorphism and gastric cancer susceptibility:a meta-analysis[J].BMC Med Genet,2014,15(8):117.
[44]Xu T,Zhu Y,Wei Q K,et al.A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma[J].Carcinogenesis,2008,29(11):2126-2131.
[45]Mao Y,Li Y,Jing F,et al.Association of a genetic variant in microRNA-146a with risk of colorectal cancer:a populationbased case-control study[J].Tumour Biol,2014,35(7):6961-6967.
[46]Ji H H,Hong-Luo,Huang G L,et al.Association between microRNA-196 a2 rs11614913,microRNA-146a rs2910164,and microRNA-423 rs6505162 polymorphisms and esophageal cancer risk:A meta-analysis[J].Meta Gene,2015,3:14-25.
[47]Wan D,Gu W,Xu G,et al.Effects of common polymorphisms rs2910164 in miR-146a and rs11614913 in miR-196 a2 on susceptibility to colorectal cancer:a systematic review metaanalysis[J].Clin Transl Oncol,2014,16(9):792-800.
[2]Esquelakerscher A A F J.Oncomirs-microRNAs with a role in cancer[J].Nature Reviews Cancer,2006,6(4):259-269.
[3]Hwang H W,Mendell J T.MicroRNAs in cell proliferation,cell death,and tumorigenesis.[J].British Journal of Cancer,2006,94(6):776-780.
[4]Okada H,Kohanbash G,Lotze M T.MicroRNAs in Immune Regulation-Opportunities for Cancer Immunotherapy[J].International Journal of Biochemistry&Cell Biology,2010,42(8):1256.
[5]Bartel D P.MicroRNAs:genomics,biogenesis,mechanism,and function[J].Cell,2004,116(2):281-297.
[6]Lewis B P,Shih I,Jones-Rhoades M W,et al.Prediction of Mammalian MicroRNA Targets[J].2003,115(7):787-798.
[7]Bhaumik D,Scott G K,Schokrpur S,et al.Expression of microRNA-146 suppresses NF-κB activity with reduction of metastatic potential in breast cancer cells[J].Oncogene,2008,27(42):5643-5647.
[8]Taganov K D,Boldin M P,Chang K J,et al.NF-kappaB-dependent induction of microRNA miR-146,an inhibitor targeted to signaling proteins of innate immune responses[J].Proc Natl Acad Sci U S A,2006,103(33):12481-12486.
[9]Lin S L,Chiang A,Chang D,et al.Loss of mir-146a function in hormone-refractory prostate cancer[J].RNA,2008,14(3):417-424.
[10]Hurst D R,Edmonds M D,Scott G K,et al.Breast Cancer Metastasis Suppressor 1 Up-regulates miR-146,Which Suppresses Breast Cancer Metastasis[J].Cancer Research,2009,69(4):1279-1283.
[11]Mei J,Bachoo R,Zhang C L.MicroRNA-146a inhibits glioma development by targeting Notch1[J].Mol Cell Biol,2011,31(17):3584-3592.
[12]Qiu Z,Li H,Wang J,et al.miR-146a and miR-146b in the diagnosis and prognosis of papillary thyroid carcinoma[J].Oncol Rep,2017,38(5):2735-2740.
[13]Min S K,Jung S Y,Kang H K,et al.Functional diversity of miR-146a-5p and TRAF6 in normal and oral cancer cells.[J].International Journal of Oncology,2017,51(5):1541.
[14]Torre L A,Bray F,Siegel R L,et al.Global cancer statistics,2012[J].CA Cancer J Clin,2015,65(2):87-108.
[15]MD W C P,Zheng R,Baade P D,et al.Cancer statistics in China,2015[J].CA:A Cancer Journal for Clinicians,2016,66(2):115-132.
[16]Wang C,Guan S,Liu F,et al.Prognostic and diagnostic potential of miR-146a in oesophageal squamous cell carcinoma[J].Br J Cancer,2016,114(3):290-297.
[17]Liu H,Ren G,Zhu L,et al.The upregulation of miRNA-146a inhibited biological behaviors of ESCC through inhibition of IRS2[J].Tumour Biol,2016,37(4):4641-4647.
[18]Wang C,Zhang W,Zhang L,et al.miR-146a-5p mediates epithelial-mesenchymal transition of oesophageal squamous cell carcinoma via targeting Notch2[J].Br J Cancer,2018,118(6):e12.
[19]金丽艳,陈德玉,毛朝明.miR-146a在食管鳞癌中的表达及意义[J].江苏大学学报(医学版),2012,22(5):422-425.
[20]Layke John C.,Lopez Peter P.胃癌:诊断和治疗方案的选择[J].中国全科医学,2015(3):248-249.
[21]Kogo R,Mimori K,Tanaka F,et al.Clinical Significance of miR-146a in Gastric Cancer Cases[J].Clinical Cancer Research,2011,17(13):4277-4284.
[22]Hou Z,Yin H,Chen C,et al.microRNA-146a targets the L1cell adhesion molecule and suppresses the metastatic potential of gastric cancer[J].Mol Med Rep,2012,6(3):501-506.
[23]Yao Q,Cao Z,Tu C,et al.MicroRNA-146a acts as a metastasis suppressor in gastric cancer by targeting WASF2[J].Cancer Lett,2013,335(1):219-224.
[24]张伟,周林,韩东升,等.miR-146a抑制胃癌细胞转移潜能机制探讨[J].中华肿瘤防治杂志,2015,22(19):1512-1517.
[25]Zhou L,Zhao X,Han Y,et al.Regulation of UHRF1 by miR-146a/b modulates gastric cancer invasion and metastasis.[J].Faseb Journal Official Publication of the Federation of American Societies for Experimental Biology,2013,27(12):4929-4939.
[26]Sha M,Ye J,Zhang L X,et al.Celastrol induces apoptosis of gastric cancer cells by miR-146a inhibition of NF-kappaBactivity[J].Cancer Cell Int,2013,13(1):50.
[27]Xiao B,Zhu E D,Li N,et al.Increased miR-146a in gastric cancer directly targets SMAD4 and is involved in modulating cell proliferation and apoptosis[J].Oncol Rep,2012,27(2):559-566.
[28]Crone S G,Jacobsen A,Federspiel B,et al.microRNA-146a inhibits G protein-coupled receptor-mediated activation of NF-κB by targeting CARD10 and COPS8 in gastric cancer[J].Molecular Cancer,2012,11(1):1-14.
[29]Rong M,He R,Dang Y,et al.Expression and clinicopathological significance of miR-146a in hepatocellular carcinoma tissues[J].Upsala Journal of Medical Sciences,2013,119(1):19-24.
[30]Zhang Z,Zhang Y,Sun X,et al.microRNA-146a inhibits cancer metastasis by downregulating VEGF through dual pathways in hepatocellular carcinoma[J].Molecular Cancer,2015,14(1):5.
[31]Huang S,He R,Rong M,et al.Synergistic effect of MiR-146a mimic and cetuximab on hepatocellular carcinoma cells.[J].Biomed Research International,2014,2014(6):384121.
[32]Li Y,VandenBoom T G,Wang Z,et al.miR-146a Suppresses Invasion of Pancreatic Cancer Cells[J].Cancer Research,2010,70(4):1486-1495.
[33]Ali S,Ahmad A,Aboukameel A,et al.Deregulation of miR-146a expression in a mouse model of pancreatic cancer affecting EGFR signaling[J].Cancer Lett,2014,351(1):134-142.
[34]RR A F A N.Diagnostic microRNA markers to screen for sporadic human colon cancer in stool:I.Proof of principle.[J].Cancer Genomics&Proteomics,2013,10(3):93-113.
[35]Sathyanarayanan A,Chandrasekaran K S,Karunagaran D.microRNA-146a inhibits proliferation,migration and invasion of human cervical and colorectal cancer cells[J].Biochem Biophys Res Commun,2016,480(4):528-533.
[36]Lu D,Yao Q,Zhan C,et al.MicroRNA-146a promote cell migration and invasion in human colorectal cancer via carboxypeptidase M/src-FAK pathway[J].Oncotarget,2017,8(14):22674-22684.
[37]Bleau A M,Redrado M,Nistal-Villan E,et al.miR-146a targets c-met and abolishes colorectal cancer liver metastasis[J].Cancer Lett,2018,414:257-267.
[38]Omrane I,Kourda N,Stambouli N,et al.MicroRNAs 146a and147 b Biomarkers for Colorectal Tumor’s Localization[J].BioMed Research International,2014,2014:1-9.
[39]Khorrami S,Zavaran H A,Mowla S J,et al.MicroRNA-146a induces immune suppression and drug-resistant colorectal cancer cells[J].Tumour Biol,2017,39(5):1393391299.
[40]Shastry B S.SNPs:impact on gene function and phenotype.[J].Methods in Molecular Biology,2009,578(578):3.
[41]Hu Y,Yu C Y,Wang J L,et al.MicroRNA sequence polymorphisms and the risk of different types of cancer[J].Scientific Reports,2014,4(4):3648.
[42]Guo H,Wang K,Xiong G,et al.A functional varient in microRNA-146a is associated with risk of esophageal squamous cell carcinoma in Chinese Han[J].Fam Cancer,2010,9(4):599-603.
[43]Xu Z,Zhang L,Cao H,et al.MiR-146a rs2910164 G/Cpolymorphism and gastric cancer susceptibility:a meta-analysis[J].BMC Med Genet,2014,15(8):117.
[44]Xu T,Zhu Y,Wei Q K,et al.A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma[J].Carcinogenesis,2008,29(11):2126-2131.
[45]Mao Y,Li Y,Jing F,et al.Association of a genetic variant in microRNA-146a with risk of colorectal cancer:a populationbased case-control study[J].Tumour Biol,2014,35(7):6961-6967.
[46]Ji H H,Hong-Luo,Huang G L,et al.Association between microRNA-196 a2 rs11614913,microRNA-146a rs2910164,and microRNA-423 rs6505162 polymorphisms and esophageal cancer risk:A meta-analysis[J].Meta Gene,2015,3:14-25.
[47]Wan D,Gu W,Xu G,et al.Effects of common polymorphisms rs2910164 in miR-146a and rs11614913 in miR-196 a2 on susceptibility to colorectal cancer:a systematic review metaanalysis[J].Clin Transl Oncol,2014,16(9):792-800.