Login Register Cart 0
Generic placeholder image

当代肿瘤药物靶点

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in English
Research Article

cdk相关Cullin 1促进胶质母细胞瘤细胞增殖和抑制细胞凋亡

卷 21, 期 10, 2021

发表于: 02 June, 2021

页: [870 - 880] 页: 11

弟呕挨: 10.2174/1568009621666210602164225

价格: $65

摘要

背景:胶质瘤是成人最常见的颅内原发肿瘤，其病理机制和分子特征仍在研究中。cdk相关cullin 1 (CACUL1)已被证明可以调节大肠癌、肺癌和胃癌的发展。 目的:探讨CACUL1在人脑胶质瘤发病机制中的作用。 方法:采用免疫组化方法检测人脑胶质瘤组织芯片中CACUL1水平。用CACUL1 siRNA转染两株胶质母细胞瘤细胞株U87和U251，通过CCK8、流式细胞仪和Western blot检测细胞增殖、细胞周期、细胞凋亡以及调控分子cyclinE1、cyclinA2、CDK2、p21、Bcl2和Bax。 结果:CACUL1在胶质瘤组织中的表达明显高于正常脑组织。下调CACUL1抑制胶质母细胞瘤细胞增殖，诱导细胞凋亡，导致胶质母细胞瘤细胞G1/S过渡阻滞。U87和U251细胞中，与非靶向siRNA组相比，CACUL1 siRNA组细胞周期相关蛋白CDK2、cyclinE1和cyclinA2显著降低，而U87细胞中CDK抑制蛋白p21升高。Bcl-2/Bax比值显著降低。 结论:CACUL1可促进胶质瘤细胞增殖，抑制胶质瘤细胞凋亡，可能作为胶质瘤的潜在癌基因。

关键词: CACUL1，胶质瘤，增殖，凋亡，CDK2，细胞周期。

« Previous Next »
图形摘要

[1]
Chertok, B.; David, A.E.; Yang, V.C. Polyethyleneimine-modified iron oxide nanoparticles for brain tumor drug delivery using magnetic targeting and intra-carotid administration. Biomaterials, 2010, 31(24), 6317-6324.
[http://dx.doi.org/10.1016/j.biomaterials.2010.04.043] [PMID: 20494439]
[2]
Jain, A.; Betancur, M.; Patel, G.D.; Valmikinathan, C.M.; Mukhatyar, V.J.; Vakharia, A.; Pai, S.B.; Brahma, B.; MacDonald, T.J.; Bellamkonda, R.V. Guiding intracortical brain tumour cells to an extracortical cytotoxic hydrogel using aligned polymeric nanofibres. Nat. Mater., 2014, 13(3), 308-316.
[http://dx.doi.org/10.1038/nmat3878] [PMID: 24531400]
[3]
Ostrom, Q.T.; Gittleman, H.; Truitt, G.; Boscia, A.; Kruchko, C.; Barnholtz-Sloan, J.S. CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the united states in 2011-2015. Neuro Oncol, 2018, 20(suppl_4), iv1-iv86.
[http://dx.doi.org/10.1093/neuonc/noy131] [PMID: 30445539]
[4]
Bilmin, K.; Kujawska, T.; Grieb, P. Sonodynamic therapy for gliomas. Perspectives and Prospects of Selective Sonosensitization of Glioma Cells, 2019, 8.
[5]
Gusyatiner, O.; Hegi, M.E. Glioma epigenetics: From subclassification to novel treatment options. Semin. Cancer Biol., 2018, 51, 50-58.
[http://dx.doi.org/10.1016/j.semcancer.2017.11.010] [PMID: 29170066]
[6]
Kong, Y.; Nan, K.; Yin, Y. Identification and characterization of CAC1 as a novel CDK2-associated cullin. Cell Cycle, 2009, 8(21), 3552-3561.
[http://dx.doi.org/10.4161/cc.8.21.9955] [PMID: 19829063]
[7]
Chen, T.J.; Gao, F.; Yang, T.; Thakur, A.; Ren, H.; Li, Y.; Zhang, S.; Wang, T.; Chen, M.W. CDK-associated Cullin 1 promotes cell proliferation with activation of ERK1/2 in human lung cancer A549 cells. Biochem. Biophys. Res. Commun., 2013, 437(1), 108-113.
[http://dx.doi.org/10.1016/j.bbrc.2013.06.048] [PMID: 23806693]
[8]
Zheng, Q.; Zhao, L.Y.; Kong, Y.; Nan, K.J.; Yao, Y.; Liao, Z.J. CDK-associated Cullin 1 can promote cell proliferation and inhibit cisplatin-induced apoptosis in the AGS gastric cancer cell line. World J. Surg. Oncol., 2013, 11, 5.
[http://dx.doi.org/10.1186/1477-7819-11-5] [PMID: 23311997]
[9]
Kong, Y.; Bai, P.S.; Sun, H.; Nan, K.J. Expression of the newly identified gene CAC1 in the hippocampus of Alzheimer’s disease patients. J. Mol. Neurosci., 2012, 47(2), 207-218.
[http://dx.doi.org/10.1007/s12031-012-9717-5] [PMID: 22415352]
[10]
Schenk, R.L.; Strasser, A.; Dewson, G. BCL-2: Long and winding path from discovery to therapeutic target. Biochem. Biophys. Res. Commun., 2017, 482(3), 459-469.
[http://dx.doi.org/10.1016/j.bbrc.2016.10.100] [PMID: 28212732]
[11]
Huang, R.; Qian, D.; Hu, M.; Zhang, X.; Song, J.; Li, L.; Chen, H.; Wang, B. Association between human cytomegalovirus infection and histone acetylation level in various histological types of glioma. Oncol. Lett., 2015, 10(5), 2812-2820.
[http://dx.doi.org/10.3892/ol.2015.3638] [PMID: 26722247]
[12]
Sarikas, A.; Hartmann, T.; Pan, Z.Q. The cullin protein family. Genome Biol., 2011, 12(4), 220.
[http://dx.doi.org/10.1186/gb-2011-12-4-220] [PMID: 21554755]
[13]
Lee, J.; Zhou, P. Cullins and cancer. Genes Cancer, 2010, 1(7), 690-699.
[http://dx.doi.org/10.1177/1947601910382899] [PMID: 21127736]
[14]
Hochegger, H.; Takeda, S.; Hunt, T. Cyclin-dependent kinases and cell-cycle transitions: Does one fit all? Nat. Rev. Mol. Cell Biol., 2008, 9(11), 910-916.
[http://dx.doi.org/10.1038/nrm2510] [PMID: 18813291]
[15]
el-Deiry, W.S.; Tokino, T.; Velculescu, V.E.; Levy, D.B.; Parsons, R.; Trent, J.M.; Lin, D.; Mercer, W.E.; Kinzler, K.W.; Vogelstein, B. WAF1, a potential mediator of p53 tumor suppression. Cell, 1993, 75(4), 817-825.
[http://dx.doi.org/10.1016/0092-8674(93)90500-P] [PMID: 8242752]
[16]
Owens, D.M.; Keyse, S.M. Differential regulation of MAP kinase signalling by dual-specificity protein phosphatases. Oncogene, 2007, 26(22), 3203-3213.
[http://dx.doi.org/10.1038/sj.onc.1210412] [PMID: 17496916]
[17]
Abbas, T.; Dutta, A. p21 in cancer: Intricate networks and multiple activities. Nat. Rev. Cancer, 2009, 9(6), 400-414.
[http://dx.doi.org/10.1038/nrc2657] [PMID: 19440234]
[18]
Viale, A.; De Franco, F.; Orleth, A.; Cambiaghi, V.; Giuliani, V.; Bossi, D.; Ronchini, C.; Ronzoni, S.; Muradore, I.; Monestiroli, S.; Gobbi, A.; Alcalay, M.; Minucci, S.; Pelicci, P.G. Cell-cycle restriction limits DNA damage and maintains self-renewal of leukaemia stem cells. Nature, 2009, 457(7225), 51-56.
[http://dx.doi.org/10.1038/nature07618] [PMID: 19122635]
[19]
Ishii, N.; Maier, D.; Merlo, A.; Tada, M.; Sawamura, Y.; Diserens, A.C.; Van Meir, E.G. Frequent co-alterations of TP53, p16/CDKN2A, p14ARF, PTEN tumor suppressor genes in human glioma cell lines. Brain Pathol., 1999, 9(3), 469-479.
[http://dx.doi.org/10.1111/j.1750-3639.1999.tb00536.x] [PMID: 10416987]
[20]
Yip, K.W.; Reed, J.C. Bcl-2 family proteins and cancer. Oncogene, 2008, 27(50), 6398-6406.
[http://dx.doi.org/10.1038/onc.2008.307] [PMID: 18955968]
[21]
Mohan, S.; Abdelwahab, S.I.; Kamalidehghan, B.; Syam, S.; May, K.S.; Harmal, N.S.; Shafifiyaz, N.; Hadi, A.H.; Hashim, N.M.; Rahmani, M.; Taha, M.M.; Cheah, S.C.; Zajmi, A. Involvement of NF-κB and Bcl2/Bax signaling pathways in the apoptosis of MCF7 cells induced by a xanthone compound Pyranocycloartobiloxanthone A. Phytomedicine, 2012, 19(11), 1007-1015.
[http://dx.doi.org/10.1016/j.phymed.2012.05.012] [PMID: 22739412]
[22]
Vucicevic, K.; Jakovljevic, V.; Colovic, N.; Tosic, N.; Kostic, T.; Glumac, I.; Pavlovic, S.; Karan-Djurasevic, T.; Colovic, M. Association of Bax expression and Bcl2/Bax ratio with clinical and molecular prognostic markers in chronic lymphocytic leukemia. J. Med. Biochem., 2016, 35(2), 150-157.
[http://dx.doi.org/10.1515/jomb-2015-0017] [PMID: 28356875]
[23]
Tsujimoto, Y. Role of Bcl-2 family proteins in apoptosis: Apoptosomes or mitochondria? Genes Cells, 1998, 3(11), 697-707.
[http://dx.doi.org/10.1046/j.1365-2443.1998.00223.x] [PMID: 9990505]

Rights & Permissions Print Cite
Article Metrics
23
2
© 2025 Bentham Science Publishers | Privacy Policy