hnRNPA2/B1在恶性肿瘤中的研究进展
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摘要
核内不均一核糖核蛋白(hn RNPs)是一类RNA结合蛋白,主要参与RNA剪切、m RNA的加工、端粒合成、DNA修复、基因表达调控及蛋白质翻译等复杂多样的生物进程。hn RNPA2/B1属于该蛋白家族中的成员之一,其在人体大多数组织中表达且具有多种功能。研究发现hn RNPA2/B1在多种恶性肿瘤中均存在差异性表达,并且可参与调控基因的表达、促进增殖与迁移能力、抑制凋亡及调控肿瘤耐药,在恶性肿瘤的诊断、治疗以及预后判断等方面都具有重要的临床价值。本文就hn RNPA2/B1在肺癌、乳腺癌、胰腺癌及肝癌等多种恶性肿瘤中的研究进展作一综述。
Heterogeneous nuclear ribonucleoproteins(hnRNPs) are a group of RNA-binding proteins that play a key role in complex and various biological processes such as RNA splicing, mRNA processing, telomere synthesis, modulation of gene expression, translation of mRNAs. Heteregeneous nuclear ribonucleoprotein A2/B1(hnRNPA2/B1) is a member of this proteins family. hn RNPA2/B1 abundantly and ubiquitously expresses in most human tissues and has various functions. Researches indicate that hn RNPA2/B1 is abnormally expressed in diverse malignant tumors, and it can modulate the expression of genes, promote the abilities of proliferation and migration, inhibit apoptosis and regulate tumor resistance in tumors. It also shows that hn RNPA2/B1 has important clinical value in the diagnosis, treatment and prognosis of malignant tumors. Therefore, this paper reviews the development of hn RNPA2/B1 in diverse cancers, such as lung cancer, breast cancer, pancreatic cancer, liver cancer and so on.
Heterogeneous nuclear ribonucleoproteins(hnRNPs) are a group of RNA-binding proteins that play a key role in complex and various biological processes such as RNA splicing, mRNA processing, telomere synthesis, modulation of gene expression, translation of mRNAs. Heteregeneous nuclear ribonucleoprotein A2/B1(hnRNPA2/B1) is a member of this proteins family. hn RNPA2/B1 abundantly and ubiquitously expresses in most human tissues and has various functions. Researches indicate that hn RNPA2/B1 is abnormally expressed in diverse malignant tumors, and it can modulate the expression of genes, promote the abilities of proliferation and migration, inhibit apoptosis and regulate tumor resistance in tumors. It also shows that hn RNPA2/B1 has important clinical value in the diagnosis, treatment and prognosis of malignant tumors. Therefore, this paper reviews the development of hn RNPA2/B1 in diverse cancers, such as lung cancer, breast cancer, pancreatic cancer, liver cancer and so on.
引文
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[14]Yu PF,Kang AR,Jing LJ,et al.Long non-coding RNACACNA1G-AS1 promotes cell migration,invasion and epithelial-mesenchymal transition by HNRNPA2B1 in non-small cell lung cancer[J].Eur Rev Med Pharmacol Sci,2018,22(4):993.
[15]Hung CY,Wang YC,Chuang JY,et al.Nm23-H1-stabilized hnRNPA2/B1 promotes internal ribosomal entry site(IRES)-mediated translation of Sp1 in the lung cancer progression[J].Sci Rep,2017,7(1):9166.
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[17]Singh R,Gupta SC,Peng WX,et al.Regulation of alternative splicing of Bcl-x by BC200 contributes to breast cancer pathogenesis[J].Cell Death&Disease,2016,7(6):e2262.
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[19]Dai S,Jie Z,Huang S,et al.HNRNPA2B1 regulates the epithelial-mesenchymal transition in pancreatic cancer cells through the ERK/snail signalling pathway[J].Cancer Cell Int,2017,17:12.
[20]BarcelóC,Etchin J,Mansour MR,et al.Ribonucleoprotein HNRNPA2B1 interacts with and regulates oncogenic KRAS in pancreatic ductal adenocarcinoma cells[J].Gastroenterology,2014,147(4):882-892.
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[22]Cui H,Feng W,Sun Y,et al.Up-regulation and subcellular localization of hnRNP A2/B1 in the development of hepatocellular carcinoma[J].BMC Cancer,2010,10:356.
[23]Mizuno H,Honda M,Shirasaki T,et al.Heterogeneous nuclear ribonucleoprotein A2/B1 in association with hTERT is a potential biomarker for hepatocellular carcinoma[J].Liver Int,2012,32(7):1146-1155.
[24]Chen T,Gu C,Xue C,et al.LncRNA-uc002mbe.2 Interacting with hnRNPA2B1 Mediates AKT Deactivation and p21 Up-Regulation Induced by Trichostatin in Liver Cancer Cells[J].Front Pharmacol,2017,8:669.
[25]Wang H,Liang L,Dong Q,et al.Long noncoding RNAmiR503HG,a prognostic indicator,inhibits tumor metastasis by regulating the HNRNPA2B1/NF-κB pathway in hepatocellular carcinoma[J].Theranostics,2018:2814-2829.
[26]Deng J,Song C,Feng W,et al.Effects of hnRNP A2/B1Knockdown on Inhibition of Glioblastoma Cell Invasion,Growth and Survival[J].Mol Neurobiol,2016,53(2):1132-1144.
[27]Dai P,Wang Q,Wang W,et al.Unraveling Molecular Differences of Gastric Cancer by Label-Free Quantitative Proteomics Analysis[J].Int J Mol Sci,2016,17(1):E69.
[28]Jing GJ,Xu DH,Shi SL,et al.Aberrant expression and localization of hnRNP-A2/B1 is a common event in human gastric adenocarcinoma[J].J Gastroenterol Hepatol,2011,26(1):108-115.
[29]Shi X,Ran L,Liu Y,et al.Knockdown of hnRNP A2/B1inhibits cell proliferation,invasion and cell cycle triggering apoptosis in cervical cancer via PI3K/AKT signaling pathway[J].Oncol Rep,2018,39(3):939-950.
[2]He Y,Smith R.Nuclear functions of heterogeneous nuclear ribonucleoproteins A/B[J].Cell Mol Life Sci,2009,66(7):1239-1256.
[3]Han SP,Tang YH,Smith R.Functional diversity of the hnRNPs:past,present and perspectives[J].Biochem J,2010,430(3):379-392.
[4]Chen M,Zhang J,Manley JL.Turning on a fuel switch of cancer-nRNP proteins regulate alternative splicing of pyruvate kinase mRNA[J].Cancer Res,2010,70(22):8977-8980.
[5]Lemieux B,Blanchette M,Monette A,et al.A Function for the hn RNP A1/A2 Proteins in Transcription Elongation[J].PLoS One,2015,10(5):e0126654.
[6]El-Mazny A,Sayed M,Sharaf S.Human telomerase reverse transcriptase messenger RNA(TERT m RNA)as a tumour marker for early detection of hepatocellular carcinoma[J].Arab J Gastroenterol,2014,15(2):68-71.
[7]Wang K,Ling T,Wu H,et al.Screening of candidate tumor-suppressor genes in 3p21.3 and investigation,of the methylation of gene promoters in oral squamous cell carcinoma[J].Oncol Rep,2013,29(3):1175-1182.
[8]Chen T,Cui P,Chen H,et al.A KH-domain RNA-binding protein interacts with FIERY2/CTD phosphatase-like1 and splicing factors and is important for pre-mRNA splicing in Arabidopsis[J].PLoS Genet,2013,9(10):e1003875.
[9]Tockman MS,Mulshine JL,Piantadosi S,et al.Prospective detection of preclinical lung cancer:results from two studies of heterogeneous nuclear ribonucleoprotein A2/B1overexpression[J].Clin Cancer Res,1997,3(12 Pt 1):2237-2246.
[10]Fielding P,Turnbull L,Prime W,et al.Heterogeneous nuclear ribonucleoprotein A2/B1 up-regulation in bronchial lavage specimens:a clinical marker of early lung cancer detection[J].Clin Cancer Res,1999,5(12):4048-4052.
[11]Dowling P,Pollard D,Larkin A,et al.Abnormal levels of heterogeneous nuclear ribonucleoprotein A2B1(hn RN-PA2B1)in tumour tissue and blood samples from patients diagnosed with lung cancer[J].Mol Biosyst,2015,11(3):743-752.
[12]Dai L,Li J,Tsay JJ,et al.Identification of autoantibodies to ECH1 and HNRNPA2B1 as potential biomarkers in the early detection of lung cancer[J].Oncoimmunology,2017,6(5):e1310359.
[13]Xuan Y,Wang J,Ban L,et al.hn RNPA2/B1 activates cyclooxygenase-2 and promotes tumor growth in human lung cancers[J].Mol Oncol,2016,10(4):610-624.
[14]Yu PF,Kang AR,Jing LJ,et al.Long non-coding RNACACNA1G-AS1 promotes cell migration,invasion and epithelial-mesenchymal transition by HNRNPA2B1 in non-small cell lung cancer[J].Eur Rev Med Pharmacol Sci,2018,22(4):993.
[15]Hung CY,Wang YC,Chuang JY,et al.Nm23-H1-stabilized hnRNPA2/B1 promotes internal ribosomal entry site(IRES)-mediated translation of Sp1 in the lung cancer progression[J].Sci Rep,2017,7(1):9166.
[16]Hu Y,Sun Z,Deng J,et al.Splicing factor hnRNPA2B1contributes to tumorigenic potential of breast cancer cells through STAT3 and ERK1/2 signaling pathway[J].Tumour Biol,2017,39(3):1010428317694318.
[17]Singh R,Gupta SC,Peng WX,et al.Regulation of alternative splicing of Bcl-x by BC200 contributes to breast cancer pathogenesis[J].Cell Death&Disease,2016,7(6):e2262.
[18]Wang L,Liu HL,Li Y,et al.Proteomic analysis of pancreatic intraepithelial neoplasia and pancreatic carcinoma in rat models[J].World J Gastroenterol,2011,17(11):1434-1441.
[19]Dai S,Jie Z,Huang S,et al.HNRNPA2B1 regulates the epithelial-mesenchymal transition in pancreatic cancer cells through the ERK/snail signalling pathway[J].Cancer Cell Int,2017,17:12.
[20]BarcelóC,Etchin J,Mansour MR,et al.Ribonucleoprotein HNRNPA2B1 interacts with and regulates oncogenic KRAS in pancreatic ductal adenocarcinoma cells[J].Gastroenterology,2014,147(4):882-892.
[21]Gu WJ,Liu HL.Induction of pancreatic cancer cell apoptosis,invasion,migration,and enhancement of chemotherapy sensitivity of gemcitabine,5-FU,and oxaliplatin by hnRNP A2/B1 si RNA[J].Anticancer Drugs,2013,24(6):566-576.
[22]Cui H,Feng W,Sun Y,et al.Up-regulation and subcellular localization of hnRNP A2/B1 in the development of hepatocellular carcinoma[J].BMC Cancer,2010,10:356.
[23]Mizuno H,Honda M,Shirasaki T,et al.Heterogeneous nuclear ribonucleoprotein A2/B1 in association with hTERT is a potential biomarker for hepatocellular carcinoma[J].Liver Int,2012,32(7):1146-1155.
[24]Chen T,Gu C,Xue C,et al.LncRNA-uc002mbe.2 Interacting with hnRNPA2B1 Mediates AKT Deactivation and p21 Up-Regulation Induced by Trichostatin in Liver Cancer Cells[J].Front Pharmacol,2017,8:669.
[25]Wang H,Liang L,Dong Q,et al.Long noncoding RNAmiR503HG,a prognostic indicator,inhibits tumor metastasis by regulating the HNRNPA2B1/NF-κB pathway in hepatocellular carcinoma[J].Theranostics,2018:2814-2829.
[26]Deng J,Song C,Feng W,et al.Effects of hnRNP A2/B1Knockdown on Inhibition of Glioblastoma Cell Invasion,Growth and Survival[J].Mol Neurobiol,2016,53(2):1132-1144.
[27]Dai P,Wang Q,Wang W,et al.Unraveling Molecular Differences of Gastric Cancer by Label-Free Quantitative Proteomics Analysis[J].Int J Mol Sci,2016,17(1):E69.
[28]Jing GJ,Xu DH,Shi SL,et al.Aberrant expression and localization of hnRNP-A2/B1 is a common event in human gastric adenocarcinoma[J].J Gastroenterol Hepatol,2011,26(1):108-115.
[29]Shi X,Ran L,Liu Y,et al.Knockdown of hnRNP A2/B1inhibits cell proliferation,invasion and cell cycle triggering apoptosis in cervical cancer via PI3K/AKT signaling pathway[J].Oncol Rep,2018,39(3):939-950.