MiR-143 acts as a tumor suppressor by targeting N-RAS and enhances temozolomide-induced apoptosis in glioma.
MiR-143 acts as a tumor suppressor by targeting N-RAS and enhances temozolomide-induced apoptosis in glioma.
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MiR-143 通过靶向 N-RAS 发挥肿瘤抑制因子的作用，并增强替莫唑胺诱导的神经胶质瘤细胞凋亡
DOI：
10.18632/oncotarget.2116
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发表时间：
2014-07-30
期刊：
影响因子：
--
通讯作者：
Jiang BH
中科院分区：
文献类型：
--
作者：
Wang L;Shi ZM;Jiang CF;Liu X;Chen QD;Qian X;Li DM;Ge X;Wang XF;Liu LZ;You YP;Liu N;Jiang BH
MicroRNAs(MiRNAs)在RAS驱动的胶质瘤中的治疗应用是有价值的，但其具体的作用和功能尚未完全阐明。在这里，我们首次报道miR-143直接靶向神经母细胞瘤RAS病毒癌基因同源基因(N-RAS)，并在胶质瘤中发挥肿瘤抑制作用。MiR-143过表达可降低N-RAS的表达，抑制PI3K/AKT、MAPK/ERK信号转导，减少p65在细胞核内的积聚。在人类临床标本中，当观察到N-RAS表达不良时，miR-143表达下调。此外，在体外和体内，miR-143过表达可减少胶质瘤细胞的迁移、侵袭、管状形成，减缓肿瘤生长和血管生成，并与N-RAS下调有关。最后，miR-143还使胶质瘤细胞对替莫唑胺(TMZ)敏感，替莫唑胺是治疗胶质瘤的一线药物。综上所述，我们的结果首次证明miR-143通过抑制N-RAS在失活RAS信号通路中发挥重要作用，这可能为治疗胶质瘤和其他RAS驱动的癌症提供一种新的治疗策略。
Therapeutic applications of microRNAs (miRNAs) in RAS-driven glioma were valuable, but their specific roles and functions have yet to be fully elucidated. Here, we firstly report that miR-143 directly targets the neuroblastoma RAS viral oncogene homolog (N-RAS) and functions as a tumor-suppressor in glioma. Overexpression of miR-143 decreased the expression of N-RAS, inhibited PI3K/AKT, MAPK/ERK signaling, and attenuated the accumulation of p65 in nucleus of glioma cells. In human clinical specimens, miR-143 was downregulated where an adverse with N-RAS expression was observed. Furthermore, overexpression of miR-143 decreased glioma cell migration, invasion, tube formation and slowed tumor growth and angiogenesis in a manner associated with N-RAS downregulation in vitro and in vivo. Finally, miR-143 also sensitizes glioma cells to temozolomide (TMZ),the first-line drug for glioma treatment. Taken together, for the first time, our results demonstrate that miR-143 plays a significant role in inactivating the RAS signaling pathway through the inhibition of N-RAS, which may provide a novel therapeutic strategy for treatment of glioma and other RAS-driven cancers.
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影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
64.8
作者：
Cordes KR;Sheehy NT;White MP;Berry EC;Morton SU;Muth AN;Lee TH;Miano JM;Ivey KN;Srivastava D
通讯作者：
Srivastava D
miR-216b通过靶向KRAS抑制鼻咽癌中的肿瘤生长和侵袭
影响因子：
4
作者：
Deng, Min;Tang, Hailin;Li, Guiyuan
通讯作者：
Li, Guiyuan
内皮 p70 S6 激酶 1 调节肿瘤血管生成
影响因子：
11.2
作者：
Liu, Ling-Zhi;Zheng, Jenny Z.;Jiang, Bing-Hua
通讯作者：
Jiang, Bing-Hua
影响因子：
2.7
作者：
Akao, Yukihiro;Nakagawa, Yoshihito;Naoe, Tomoki
通讯作者：
Naoe, Tomoki