miR-216b suppresses tumor growth and invasion by targeting KRAS in nasopharyngeal carcinoma
miR-216b suppresses tumor growth and invasion by targeting KRAS in nasopharyngeal carcinoma
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miR-216b通过靶向KRAS抑制鼻咽癌中的肿瘤生长和侵袭
DOI：
10.1242/jcs.085050
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发表时间：
2011-09-01
影响因子：
4
通讯作者：
Li, Guiyuan
中科院分区：
文献类型：
--
作者：
Deng, Min;Tang, Hailin;Li, Guiyuan
MicroRNA（miRNAs）是一种小的非编码RNA，与包括癌症在内的多种疾病有关。在本研究中，我们发现miR-216 b在鼻咽癌（NPC）细胞系和标本中下调。miR-216 b表达降低与临床分期及淋巴结转移密切相关。miR-216 b水平与鼻咽肿瘤发生过程中KRAS蛋白水平呈负相关。此外，我们证明了miR-216 b可以与KRAS的3′非翻译区（UTR）结合并抑制KRAS蛋白的表达。体外和体内实验均显示miR-216 b可抑制鼻咽癌细胞增殖、侵袭和裸鼠肿瘤生长。miR-216 b通过抑制KRAS相关的AKT和ERK途径发挥其肿瘤抑制功能。我们的研究结果首次提供了关于miR-216 b通过靶向KRAS在NPC中作为肿瘤抑制剂的作用的重要线索。
MicroRNAs (miRNAs) are small noncoding RNAs that are involved in various diseases, including cancer. In the present study, we found that miR-216b was downregulated in nasopharyngeal carcinoma (NPC) cell lines and specimens. Decreased expression of miR-216b was directly related to advanced clinical stage and lymph node metastasis. miR-216b levels correlated inversely with levels of KRAS protein during nasopharyngeal tumorigenesis. Furthermore, we demonstrated that miR-216b can bind to the 3′ untranslated region (UTR) of KRAS and inhibit expression of the KRAS protein. Both in vitro and in vivo assays revealed that miR-216b attenuated NPC cell proliferation, invasion and tumor growth in nude mice. miR-216b exerts its tumor suppressor function through inhibition of the KRAS-related AKT and ERK pathways. Our findings provide, for the first time, significant clues regarding the role of miR-216b as a tumor suppressor by targeting KRAS in NPC.