MicroRNA-193b enhances tumor progression via down regulation of neurofibromin 1.
MicroRNA-193b enhances tumor progression via down regulation of neurofibromin 1.
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DOI：
10.1371/journal.pone.0053765
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Liu FF
中科院分区：
文献类型：
--
作者：
Lenarduzzi M;Hui AB;Alajez NM;Shi W;Williams J;Yue S;O'Sullivan B;Liu FF
尽管头颈部鳞状细胞癌（HNSCC）的治疗方法有所改进，但临床结果仍然令人失望，5年总生存率徘徊在40- 50%左右，强调迫切需要更好地了解这种疾病的生物学基础。我们选择通过研究micro-RNAs（miRNAs）在HNSCC中的作用来应对这一挑战。MiR-193 b在我们实验室之前进行的全球miRNA谱研究中被鉴定为过表达的miRNA，并在HNSCC细胞系中得到证实。FaDu癌细胞中miR-193 b的体外敲低显著降低了细胞增殖、迁移和侵袭，沿着体内抑制的肿瘤形成。通过整合计算机预测算法与体外实验mRNA分析，加上临床标本的mRNA表达数据，神经纤维蛋白1（NF 1）被确定为miR-193 b的靶点。一致地，miR-193 b敲低显著降低NF 1转录物和蛋白水平。荧光素酶报告基因测定证实了miR-193 b与NF 1的直接相互作用。此外，NF 1的下游靶点p-ERK在miR-193 b敲低后也受到抑制。用p-ERK抑制剂（U 0126）处理的FaDu细胞表型模仿了用miR-193 b敲低观察到的细胞增殖、迁移和侵袭的降低。最后，与低miR-193 b表达的患者相比，肿瘤表达高水平miR-193 b的HNSCC患者的无病生存率较低。我们的研究结果将miR-193 b确定为HNSCC中潜在的新型预后标志物，其通过下调NF 1驱动肿瘤进展，进而导致ERK激活，导致增殖，迁移，侵袭和肿瘤形成。
Despite improvements in therapeutic approaches for head and neck squamous cell carcinomas (HNSCC), clinical outcome has remained disappointing, with 5-year overall survival rates hovering around 40–50%, underscoring an urgent need to better understand the biological bases of this disease. We chose to address this challenge by studying the role of micro-RNAs (miRNAs) in HNSCC. MiR-193b was identified as an over-expressed miRNA from global miRNA profiling studies previously conducted in our lab, and confirmed in HNSCC cell lines. In vitro knockdown of miR-193b in FaDu cancer cells substantially reduced cell proliferation, migration and invasion, along with suppressed tumour formation in vivo. By integrating in silico prediction algorithms with in vitro experimental mRNA profilings, plus mRNA expression data of clinical specimens, neurofibromin 1 (NF1) was identified to be a target of miR-193b. Concordantly, miR-193b knockdown decreased NF1 transcript and protein levels significantly. Luciferase reporter assays confirmed the direct interaction of miR-193b with NF1. Moreover, p-ERK, a downstream target of NF1 was also suppressed after miR-193b knockdown. FaDu cells treated with a p-ERK inhibitor (U0126) phenocopied the reduced cell proliferation, migration and invasion observed with miR-193b knockdown. Finally, HNSCC patients whose tumours expressed high levels of miR-193b experienced a lower disease-free survival compared to patients with low miR-193b expression. Our findings identified miR-193b as a potentially novel prognostic marker in HNSCC that drives tumour progression via down-regulating NF1, in turn leading to activation of ERK, resulting in proliferation, migration, invasion, and tumour formation.
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影响因子：
64.5
作者：
LI, Y;BOLLAG, G;CAWTHON, R
通讯作者：
CAWTHON, R
DOI：
10.1158/1078-0432.ccr-08-3131
发表时间：
2009-04-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Avissar M;Christensen BC;Kelsey KT;Marsit CJ
通讯作者：
Marsit CJ
影响因子：
6.1
作者：
Cassell A;Grandis JR
通讯作者：
Grandis JR
影响因子：
64.8
作者：
Chin, L.;Meyerson, M.;Aldape, K.;Bigner, D.;Mikkelsen, T.;VandenBerg, S.;Kahn, A.;Penny, R.;Ferguson, M. L.;Gerhard, D. S.;Getz, G.;Brennan, C.;Taylor, B. S.;Winckler, W.;Park, P.;Ladanyi, M.;Hoadley, K. A.;Verhaak, R. G. W.;Hayes, D. N.;Spellman, Paul T.;Absher, D.;Weir, B. A.;Ding, L.;Wheeler, D.;Lawrence, M. S.;Cibulskis, K.;Mardis, E.;Zhang, Jinghui;Wilson, R. K.;Donehower, L.;Wheeler, D. A.;Purdom, E.;Wallis, J.;Laird, P. W.;Herman, J. G.;Schuebel, K. E.;Weisenberger, D. J.;Baylin, S. B.;Schultz, N.;Yao, Jun;Wiedemeyer, R.;Weinstein, J.;Sander, C.;Gibbs, R. A.;Gray, J.;Kucherlapati, R.;Lander, E. S.;Myers, R. M.;Perou, C. M.;McLendon, Roger;Friedman, Allan;Van Meir, Erwin G;Brat, Daniel J;Mastrogianakis, Gena Marie;Olson, Jeffrey J;Lehman, Norman;Yung, W. K. Alfred;Bogler, Oliver;Berger, Mitchel;Prados, Michael;Muzny, Donna;Morgan, Margaret;Scherer, Steve;Sabo, Aniko;Nazareth, Lynn;Lewis, Lora;Hall, Otis;Zhu, Yiming;Ren, Yanru;Alvi, Omar;Yao, Jiqiang;Hawes, Alicia;Jhangiani, Shalini;Fowler, Gerald;San Lucas, Anthony;Kovar, Christie;Cree, Andrew;Dinh, Huyen;Santibanez, Jireh;Joshi, Vandita;Gonzalez-Garay, Manuel L.;Miller, Christopher A.;Milosavljevic, Aleksandar;Sougnez, Carrie;Fennell, Tim;Mahan, Scott;Wilkinson, Jane;Ziaugra, Liuda;Onofrio, Robert;Bloom, Toby;Nicol, Rob;Ardlie, Kristin;Baldwin, Jennifer;Gabriel, Stacey;Fulton, Robert S.;McLellan, Michael D.;Larson, David E.;Shi, Xiaoqi;Abbott, Rachel;Fulton, Lucinda;Chen, Ken;Koboldt, Daniel C.;Wendl, Michael C.;Meyer, Rick;Tang, Yuzhu;Lin, Ling;Osborne, John R.;Dunford-Shore, Brian H.;Miner, Tracie L.;Delehaunty, Kim;Markovic, Chris;Swift, Gary;Courtney, William;Pohl, Craig;Abbott, Scott;Hawkins, Amy;Leong, Shin;Haipek, Carrie;Schmidt, Heather;Wiechert, Maddy;Vickery, Tammi;Scott, Sacha;Dooling, David J.;Chinwalla, Asif;Weinstock, George M.;O'Kelly, Michael;Robinson, Jim;Alexe, Gabriele;Beroukhim, Rameen;Carter, Scott;Chiang, Derek;Gould, Josh;Gupta, Supriya;Korn, Josh;Mermel, Craig;Mesirov, Jill;Monti, Stefano;Nguyen, Huy;Parkin, Melissa;Reich, Michael;Stransky, Nicolas;Garraway, Levi;Golub, Todd;Protopopov, Alexei;Perna, Ilana;Aronson, Sandy;Sathiamoorthy, Narayan;Ren, Georgia;Kim, Hyunsoo;Kong, Sek Won;Xiao, Yonghong;Kohane, Isaac S.;Seidman, Jon;Cope, Leslie;Pan, Fei;Van Den Berg, David;Van Neste, Leander;Yi, Joo Mi;Li, Jun Z.;Southwick, Audrey;Brady, Shannon;Aggarwal, Amita;Chung, Tisha;Sherlock, Gavin;Brooks, James D.;Jakkula, Lakshmi R.;Lapuk, Anna V.;Marr, Henry;Dorton, Shannon;Choi, Yoon Gi;Han, Ju;Ray, Amrita;Wang, Victoria;Durinck, Steffen;Robinson, Mark;Wang, Nicholas J.;Vranizan, Karen;Peng, Vivian;Van Name, Eric;Fontenay, Gerald V.;Ngai, John;Conboy, John G.;Parvin, Bahram;Feiler, Heidi S.;Speed, Terence P.;Socci, Nicholas D.;Olshen, Adam;Lash, Alex;Reva, Boris;Antipin, Yevgeniy;Stukalov, Alexey;Gross, Benjamin;Cerami, Ethan;Wang, Wei Qing;Qin, Li-Xuan;Seshan, Venkatraman E.;Villafania, Liliana;Cavatore, Magali;Borsu, Laetitia;Viale, Agnes;Gerald, William;Topal, Michael D.;Qi, Yuan;Balu, Sai;Shi, Yan;Wu, George;Bittner, Michael;Shelton, Troy;Lenkiewicz, Elizabeth;Morris, Scott;Beasley, Debbie;Sanders, Sheri;Sfeir, Robert;Chen, Jessica;Nassau, David;Feng, Larry;Hickey, Erin;Schaefer, Carl;Madhavan, Subha;Buetow, Ken;Barker, Anna;Vockley, Joseph;Compton, Carolyn;Vaught, Jim;Fielding, Peter;Collins, Francis;Good, Peter;Guyer, Mark;Ozenberger, Brad;Peterson, Jane;Thomson, Elizabeth
通讯作者：
Thomson, Elizabeth
影响因子：
11.5
作者：
Hui, Angela B. Y.;Yue, Shijun;Liu, Fei-Fei
通讯作者：
Liu, Fei-Fei