MicroRNA-335 acts as a metastasis suppressor in gastric cancer by targeting Bcl-w and specificity protein 1.
MicroRNA-335 acts as a metastasis suppressor in gastric cancer by targeting Bcl-w and specificity protein 1.
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MicroRNA-335 通过靶向 Bcl-w 和特异性蛋白 1 作为胃癌转移抑制剂
DOI：
10.1038/onc.2011.340
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发表时间：
2012-03-15
期刊：
影响因子：
8
通讯作者：
Xu, H.
中科院分区：
文献类型：
--
作者：
Xu, Y.;Zhao, F.;Wang, Z.;Song, Y.;Luo, Y.;Zhang, X.;Jiang, L.;Sun, Z.;Miao, Z.;Xu, H.
MiR-335的异常表达在肿瘤研究中屡见不鲜，提示miR-335与肿瘤的发生、发展、转移及预后密切相关。MiR-335在胃癌中的表达及其作用尚不清楚。实时定量逆转录-聚合酶链式反应证实miR-335在4个胃癌细胞系和70例胃癌组织中的相对表达。用Transwell细胞体外迁移和Matrigel侵袭实验和体内转移形成实验检测miR-335表达对胃癌细胞侵袭转移的影响。用3-(4，5-二甲基噻唑-2-基)-2，5-二苯基四氮唑溴化法检测miR-335的表达对胃癌细胞增殖的影响。用荧光素酶报告基因分析和免疫印迹方法检测潜在的靶基因和相关途径。采用小干扰RNA基因沉默技术检测靶基因对胃癌细胞侵袭能力的影响。MIR-335在胃癌细胞系中的表达显著低于正常胃癌细胞系GES-1。MiR-335低表达与淋巴结转移、PT分期差、PN分期差和淋巴管侵犯密切相关。MiR-335过表达抑制了胃癌细胞的体内外侵袭和转移，但对细胞增殖无明显影响。此外，miR-335可能通过靶向Bclw和特异性蛋白1(SP1)来抑制胃癌的侵袭和转移。综上所述，我们的结果提供了证据，miR-335可能通过Bclw诱导的磷脂酰肌醇3-激酶-Akt-Sp1途径直接或间接靶向SP1，从而在胃癌中发挥转移抑制作用。MIR-335在胃癌不同阶段的表达改变，可能成为胃癌治疗的靶点，并可能进一步发展为潜在的预后因素。
Aberrant expression of miR-335 has been frequently reported in cancer studies, suggesting that there is a close correlation between miR-335 and cancer during its development, progression, metastasis and prognosis. The expression of miR-335 in gastric cancer and its effects are not known. Relative expression of miR-335 in 4 gastric cancer cell lines and in 70 gastric cancer tissues was confirmed by real-time quantitative reverse transcriptase-PCR compared with controls. Transwell cell migration and Matrigel invasion assay in vitro and metastasis formation assay in vivo were used to examine the effects of miR-335 expression on gastric cancer cell invasion and metastasis. The effect of miR-335 expression on gastric cancer cell proliferation was estimated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Luciferase reporter assay and western blot were used to examine the potential target genes and related pathways. Gene silencing with small-interfering RNA was used to examine the effects of target genes on gastric cancer cell invasion. miR-335 was dramatically downregulated in gastric cancer cell lines than in the normal gastric cell line GES-1. Low expression of miR-335 was significantly associated with lymph-node metastasis, poor pT stage, poor pN stage and invasion of lymphatic vessels. Overexpression of miR-335 suppressed gastric cancer cell invasion and metastasis in vitro and in vivo, but has no significant effects on cell proliferation. Furthermore, miR-335 might suppress gastric cancer invasion and metastasis by targeting Bcl-w and specificity protein 1 (SP1). Taken together, our results provide evidence that miR-335 might function as a metastasis suppressor in gastric cancer by targeting SP1 directly and indirectly through the Bcl-w-induced phosphoinositide 3-kinase-Akt-Sp1 pathway. miR-335 showing altered expression at different stages of gastric cancer could be a target for gastric cancer therapies and could be further developed as a potential prognostic factor.
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影响因子：
64.5
作者：
Bond, GL;Hu, WW;Levine, AJ
通讯作者：
Levine, AJ
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
DOI：
10.1073/pnas.0703942104
发表时间：
2007-10-09
影响因子：
11.1
作者：
Gironella, Meritxell;Seux, Mylene;Dusetti, Nelson J.
通讯作者：
Dusetti, Nelson J.
影响因子：
9.7
作者：
Liu, Tao;Tang, Hua;Li, Xin
通讯作者：
Li, Xin
DOI：
10.1073/pnas.0602266103
发表时间：
2006-05-02
影响因子：
11.1
作者：
Costinean, S;Zanesi, N;Croce, CM
通讯作者：
Croce, CM