EBV阳性与阴性NPC细胞中AKR1B10的差异表达及生物学意义Differential Expression and Biological Significance of AKR1B10 in EBV Positive and Negative NPC Cells
李海亮,阮宏莹,王海茹,李梅芳,张峻峥,羊华高
摘要(Abstract):
研究EB病毒(Epstein-Barr virus,EBV)阳性与阴性鼻咽癌(Nasopharyngeal carcinoma,NPC)细胞中醛酮还原酶家族1成员B10(AKR1B10)的差异表达及生物学意义。收集NPC组织并检测EBV感染情况及AKR1B10表达水平,比较EBV阳性与阴性NPC组织中AKR1B10表达水平的差异;培养EBV阳性的NPC细胞株HK-1和C666-1、EBV阴性的NPC细胞株CNE-1及CNE-2,检测AKR1B10的表达水平。HK-1和C666-1进行分组,给予10μmol/L、20μmol/L AKR1B10抑制剂处理,20μmol/L AKR1B10抑制剂联合对照溶剂或20μmol/L β-catenin激动剂处理,检测细胞增殖水平、侵袭数目及c-myc、MMP2、MMP9的mRNA表达水平,AKR1B10、总β-连环蛋白(β-catenin)、核β-catenin的蛋白表达水平。结果显示HK-1和C666-1细胞中AKR1B10的蛋白表达水平高于CNE-1及CNE-2;10μmol/L、20μmol/L AKR1B10抑制剂组HK-1和C666-1细胞的增殖水平、侵袭数目、c-myc、MMP2、MMP9的mRNA表达水平、核β-catenin的蛋白表达水平低于对照组(P<0.05),总β-catenin的蛋白表达水平与对照组比较无差异(P>0.05);β-catenin激动剂+AKR1B10抑制剂组HK-1和C666-1细胞的增殖水平、侵袭数目、cmyc、MMP2、MMP9的mRNA表达水平、总β-catenin及核β-catenin的蛋白表达水平高于溶剂+AKR1B10抑制剂组(P<0.05)。可以得出结论,EBV阳性NPC细胞中AKR1B10表达水平增加通过激活β-catenin入核的方式促进细胞增殖和侵袭。
关键词(KeyWords): 鼻咽癌;EB病毒;醛酮还原酶家族1成员B10;β-连环蛋白;增殖;侵袭
基金项目(Foundation):
作者(Author): 李海亮,阮宏莹,王海茹,李梅芳,张峻峥,羊华高
DOI: 10.13242/j.cnki.bingduxuebao.004365
参考文献(References):
- [1]郭蕊,马骏.鼻咽癌分期的演变与未来发展[J].中国癌症防治杂志,2020, 12(4):370-376.
- [2]付振涛,郭晓雷,张思维,曾红梅,孙可欣,陈万青,赫捷. 2014年中国鼻咽癌发病与死亡分析[J/OL].中华肿瘤杂志,2018, 40(8):566-571. DOI:10.3760/cma.j.issn.0253-3766.2018.08.002.
- [3] Yin H, Qu J, Peng Q, Gan R. Molecular mechanisms of EBV-driven cell cycle progression and oncogenesis[J/OL]. Med Microbiol Immunol, 2019, 208(5):573-583.DOI:10.1007/s00430-018-0570-1.
- [4] Cao Z, Delfino K, Tiwari V, Wang X, Hannan A,Zaidi F, McClintock A, Robinson K, Zhu Y, Gao J,Cao D, Rao K. AKR1B10 as a potential novel serum biomarker for breast cancer:a pilot study[J/OL]. Front Oncol, 2022, 12:727505-727505. DOI:10.3389/fonc.2022.727505.
- [5] Hojnik M,?uster NK, Smrkolj?,Sisinger D, Grazio SF, Verdenik I, Ri?ner TL. AKR1B1 as a prognostic biomarker of high-grade serous ovarian cancer[J/OL].Cancers(Basel), 2022, 14(3):809-809. DOI:10.3390/cancers14030809.
- [6]彭玉凤,张扬南,罗迪贤. EB病毒与鼻咽癌组织AKR1B10蛋白表达相关性分析[J/OL].中华肿瘤防治杂志,2018, 25(19):1371-1375. DOI:10.16073/j.cnki.cjcpt.2018.19.006.
- [7] Liu J, Ban H, Liu Y, Ni J. The expression and significance of AKR1B10 in laryngeal squamous cell carcinoma[J/OL]. Sci Rep, 2021, 11(1):18228-18228. DOI:10.1038/s41598-021-97648-y.
- [8] Hojnik M, Frkovi?GS, Verdenik I, Ri?ner TL.AKR1B1 and AKR1B10 as prognostic biomarkers of endometrioid endometrial carcinomas[J/OL]. Cancers(Basel), 2021, 13(14):3398-3398. DOI:10.3390/cancers13143398.
- [9]彭旭红,李佳,王玉,张健,罗伟濠,朱乐攀,胡政,吴海燕,李艳兰,段丽丽. AKR1B10在甲状腺乳头状癌组织中的表达及其临床意义[J].中国癌症防治杂志,2019,11(5):416-420.
- [10]Li M,Chen W,Yang J,Charvat H,Xie S,Li T,Ling W,Lu Y,Liu Q,Hong M. Association between solid fuel use and seropositivity against Epstein-Barr virus in a high-risk area for nasopharyngeal carcinoma[J/OL]. Environ Pollut, 2022, 304:119184-119184. DOI:10.1016/j.envpol.2022.119184.
- [11]Jicman SD, Niculet E, Lungu M, Onisor C,Rebegea L,Vesa D,Bezman L,Bujoreanu FC,Sarbu ML,Mihailov R, Fotea S, Tatu AL. Nasopharyngeal carcinoma:A new synthesis of literature data(Review)[J/OL]. Exp Ther Med, 2022, 23(2):136-136. DOI:10.3892/etm.2021.11059.
- [12]Endo S,Xia S,Suyama M,Morikawa Y,Oguri H,Hu D,Ao Y,Takahara S,Horino Y,Hayakawa Y,Hayakawa Y, Watanabe Y, Gouda H, Hara A,Kuwata K, Toyooka N, Matsunaga T, Ikari A.Synthesis of potent and selective inhibitors of Aldo-Keto Reductase 1B10 and their efficacy against proliferation,metastasis, and cisplatin resistance of lung cancer cells[J/OL]. J Med Chem. 2017;60(20):8441-8455. DOI:10.1021/acs.jmedchem.7b00830.
- [13]Huang W, Song Y, Jiang Y, Chen L,Lu H. c-Mycinduced circ-NOTCH1 promotes aggressive phenotypes of nasopharyngeal carcinoma cells by regulating the miR-34c-5p/c-Myc axis[J/OL]. Cell Biol Int, 2021, 45(7):1436-1447. DOI:10.1002/cbin.11582.
- [14]Yusuf M, Kusuma YA, Pawarti DR. Matrix metalloproteinase-9 expression and status of cervical lymph nodes in patients with nasopharyngeal carcinoma[J/OL]. Indian J Otolaryngol Head Neck Surg, 2019,71(Suppl 1):637-642. DOI:10.1007/s12070-018-1451-z.
- [15]屈佳肴,刘香婷,王玉,李佳,龚珂,段丽丽,罗文娜,罗迪贤.醛酮还原酶家族1成员B10(AKR1B10)通过激活Wnt/β-catenin通路促进乳腺癌细胞增殖[J/OL].细胞与分子免疫学杂志,2019, 35(12):1094-1100.DOI:10.13423/j.cnki.cjcmi.008873.
- [16]Zhang Y, Wang X. Targeting the Wnt/β-catenin signaling pathway in cancer[J/OL]. J Hematol Oncol,2020, 13(1):165. DOI:10.1186/s13045-020-00990-3.
- [17]Patel S, Alam A, Pant R, Chattopadhyay S. Wnt signaling and its significance within the tumor microenvironment:novel therapeutic insights[J/OL].Front Immunol, 2019, 16(10):2872. DOI:10.3389/fimmu.2019.02872.
- [18]Zhou L, Shen Y, Zhou T, Li C,Hu Y,Xiao H. The prognostic significance of β-Catenin expression in patients with nasopharyngeal carcinoma:A systematic review and meta-analysis[J/OL]. Front Genet, 2022,13:953739-953739. DOI:10.3389/fgene.2022.953739.