利用组织芯片分析DJ-1蛋白在非霍奇淋巴瘤组织中的定位表达及意义
|
摘要
DJ-1是PARK7基因编码的一种蛋白质,其过表达与许多恶性肿瘤的发生、侵袭、转移及预后密切相关。然而,有关DJ-1蛋白在非霍奇金淋巴瘤(NHL)中的表达与NHL生物学特性的关系尚未见文献报导。本文检测了61例NHL组织中DJ-1蛋白在细胞核内外的表达情况,发现DJ-1蛋白在细胞浆内高表达的情况较细胞核内更为显著(93.4%、72.1%),且都显著高于非肿瘤组织(28.6%、14.3%)。此外,DJ-1蛋白的高表达率与NHL的恶性程度正相关,DJ-1蛋白在惰性、侵袭性和高侵袭性NHL中核高表达率为52.2%、82.9%和100%;浆高表达率为82.6%、100%和100%。结果提示DJ-1蛋白在NHL细胞内的定位可能是一个动态过程,而这与肿瘤的发生和发展密切相关;DJ-1与NHL的转移和侵袭等恶性进程密切相关,DJ-1是极具潜力的NHL相关的肿瘤生物学标记物。
DJ-1/PARK7 is a gene with oncogenic potential,and its overexpression is strongly linked with the occurrence,invasion,metastasis and prognosis of numerous malignant tumors. However,the relationship between DJ-1 protein expression and the biological characteristics of non-Hodgkinlymphoma(NHL) was not previously reported in the literature.This research investigated the intracellular distribution of DJ-1 protein in NHL tissues obtained from 61 patients,finding that DJ-1 proteins located in the cytoplasm at a higher compression ratio than those in the nucleus(93.4%,72.1%,respectively),and both were remarkably higher than those in non-tumor tissues(28.6%,14.3%,respectively). In addition,tissue expression of DJ-1 protein is positive to the malignancy of NHL: for indolent,aggressive and highly aggressive NHL,DJ-1 protein expressing rates in the cytoplasm were 52.2%,82.9% and 100%,and in the nucleus were 82.6%、100% 和100%,respectively.The results indicate that the localization of DJ-1 protein in NHL cells may be a dynamic process,which is closely associated with development and progression of lymphoma; DJ-1 is closely related to malignant processes such as metastasis and invasion of NHL; DJ-1 is a promising NHL-related oncology biomarker.
DJ-1/PARK7 is a gene with oncogenic potential,and its overexpression is strongly linked with the occurrence,invasion,metastasis and prognosis of numerous malignant tumors. However,the relationship between DJ-1 protein expression and the biological characteristics of non-Hodgkinlymphoma(NHL) was not previously reported in the literature.This research investigated the intracellular distribution of DJ-1 protein in NHL tissues obtained from 61 patients,finding that DJ-1 proteins located in the cytoplasm at a higher compression ratio than those in the nucleus(93.4%,72.1%,respectively),and both were remarkably higher than those in non-tumor tissues(28.6%,14.3%,respectively). In addition,tissue expression of DJ-1 protein is positive to the malignancy of NHL: for indolent,aggressive and highly aggressive NHL,DJ-1 protein expressing rates in the cytoplasm were 52.2%,82.9% and 100%,and in the nucleus were 82.6%、100% 和100%,respectively.The results indicate that the localization of DJ-1 protein in NHL cells may be a dynamic process,which is closely associated with development and progression of lymphoma; DJ-1 is closely related to malignant processes such as metastasis and invasion of NHL; DJ-1 is a promising NHL-related oncology biomarker.
引文
[1]王娟,谭晖,苏琦.DJ-1在肿瘤中作用的研究进展[J].临床与病理杂志,2011,31(6):527-30.
[2]刘殊,王士勇,张晖,等.NIBP在结肠癌组织中的表达及临床意义[J].现代肿瘤医学,2015,23(7):974-7.
[3]付实,张琍.组织芯片技术在消化道肿瘤研究中的应用[J].中南医学科学杂志,2017,45(2):183-5.
[4]G9RNER K,HOLTORF E,WAAK J,et al.Structural determinants of the C-terminal helix-kink-helix motif essential for protein stability and survival promoting activity of DJ-1[J].J Biol Chem,2007,282(18):13680-91.
[5]CULLETON BA,LALL P,KINSELLA GK,et al.A role for the Parkinson’s disease protein DJ-1 as a chaperone and antioxidant in the anhydrobiotic nematode Panagrolaimus superbus[J].Cell Stress Chaperones,2015,20(1):121-37.
[6]KISS R,ZHU M,JóJóRT B,et al.Structural features of human DJ-1 in distinct Cys106 oxidative states and their relevance to its loss of function in disease[J].Biochim Biophys Acta,2017,1861(11 Pt A):2619-29.
[7]ISHIKAWA S,TAIRA T,TAKAHASHI-NIKI K,et al.Human DJ-1-specific transcriptional activation of tyrosine hydroxylase gene[J].J Biol Chem,2010,68(51):39718-31.
[8]JUNN E,TANIGUCHI H,JEONG B S,et al.Interaction of DJ-1with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death[J].Proc Natl Acad Sci U S A,2005,102(27):9691-96.
[9]MO J S,KIM M Y,ANN E J,et al.DJ-1 modulates UV-induced oxidative stress signaling through the suppression of MEKK1 and cell death[J].Cell Death Differ,2008,15(6):1030-41.
[10]KATO I,MAITA H,TAKAHASHI-NIKI K,et al.Oxidized DJ-1 inhibits p53 by sequestering p53 from promoters in a DNAbinding affinity-dependent manner[J].Mol Cell Biol,2013,33(2):340-59.
[11]SHINBO Y,TAIRA T,NIKI T,et al.DJ-1 restores p53 transcription activity inhibited by Topors/p53BP3.[J].Int J Oncol,2005,26(3):641-48.
[12]PTAK C,WOZNIAK RW.SUMO and Nucleocytoplasmic Transport[J].Adv Exp Med Biol,2017,963:111-26.
[13]FAN J,REN H,FEI E,et al.Sumoylation is critical for DJ-1 to repress p53 transcriptional activity[J].FEBS Lett,2008,582(7):1151-56.
[14]HE X,ZHENG Z,LI J,et al.DJ-1 promotes invasion and metastasis of pancreatic cancer cells by activating SRC/ERK/u PA[J].Carcinogenesis,2012,33(3):555-62.
[15]Han B,Wang J,Gao J,et al.DJ-1 as a potential biomarker for the early diagnosis in lung cancer patients[J].Tumour Biol,2017,39(6):1-7.
[2]刘殊,王士勇,张晖,等.NIBP在结肠癌组织中的表达及临床意义[J].现代肿瘤医学,2015,23(7):974-7.
[3]付实,张琍.组织芯片技术在消化道肿瘤研究中的应用[J].中南医学科学杂志,2017,45(2):183-5.
[4]G9RNER K,HOLTORF E,WAAK J,et al.Structural determinants of the C-terminal helix-kink-helix motif essential for protein stability and survival promoting activity of DJ-1[J].J Biol Chem,2007,282(18):13680-91.
[5]CULLETON BA,LALL P,KINSELLA GK,et al.A role for the Parkinson’s disease protein DJ-1 as a chaperone and antioxidant in the anhydrobiotic nematode Panagrolaimus superbus[J].Cell Stress Chaperones,2015,20(1):121-37.
[6]KISS R,ZHU M,JóJóRT B,et al.Structural features of human DJ-1 in distinct Cys106 oxidative states and their relevance to its loss of function in disease[J].Biochim Biophys Acta,2017,1861(11 Pt A):2619-29.
[7]ISHIKAWA S,TAIRA T,TAKAHASHI-NIKI K,et al.Human DJ-1-specific transcriptional activation of tyrosine hydroxylase gene[J].J Biol Chem,2010,68(51):39718-31.
[8]JUNN E,TANIGUCHI H,JEONG B S,et al.Interaction of DJ-1with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death[J].Proc Natl Acad Sci U S A,2005,102(27):9691-96.
[9]MO J S,KIM M Y,ANN E J,et al.DJ-1 modulates UV-induced oxidative stress signaling through the suppression of MEKK1 and cell death[J].Cell Death Differ,2008,15(6):1030-41.
[10]KATO I,MAITA H,TAKAHASHI-NIKI K,et al.Oxidized DJ-1 inhibits p53 by sequestering p53 from promoters in a DNAbinding affinity-dependent manner[J].Mol Cell Biol,2013,33(2):340-59.
[11]SHINBO Y,TAIRA T,NIKI T,et al.DJ-1 restores p53 transcription activity inhibited by Topors/p53BP3.[J].Int J Oncol,2005,26(3):641-48.
[12]PTAK C,WOZNIAK RW.SUMO and Nucleocytoplasmic Transport[J].Adv Exp Med Biol,2017,963:111-26.
[13]FAN J,REN H,FEI E,et al.Sumoylation is critical for DJ-1 to repress p53 transcriptional activity[J].FEBS Lett,2008,582(7):1151-56.
[14]HE X,ZHENG Z,LI J,et al.DJ-1 promotes invasion and metastasis of pancreatic cancer cells by activating SRC/ERK/u PA[J].Carcinogenesis,2012,33(3):555-62.
[15]Han B,Wang J,Gao J,et al.DJ-1 as a potential biomarker for the early diagnosis in lung cancer patients[J].Tumour Biol,2017,39(6):1-7.