MicroRNA-133b is a key promoter of cervical carcinoma development through the activation of the ERK and AKT1 pathways
MicroRNA-133b is a key promoter of cervical carcinoma development through the activation of the ERK and AKT1 pathways
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MicroRNA-133b 通过激活 ERK 和 AKT1 通路是宫颈癌发展的关键启动子
DOI：
10.1038/onc.2011.561
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发表时间：
2012-09-01
期刊：
影响因子：
8
通讯作者：
Cheng, J.
中科院分区：
文献类型：
--
作者：
Qin, W.;Dong, P.;Cheng, J.
我们报道升高的microRNA-133b （miR-133b）在人宫颈癌中作为致癌基因促进肿瘤发生和转移。原位杂交证实miR-133b定位于增殖的人宫颈癌细胞中，其水平在晚期逐渐升高。细胞研究表明，miR-133b通过靶向哺乳动物不育20样激酶2 （MST2）、细胞分裂控制蛋白42同源物（CDC42）和ras同源基因家族成员A (RHOA)，从而激活致瘤蛋白激酶B α (AKT1)和丝裂原活化蛋白激酶（ERK1和ERK2，这里简称ERK）信号通路，促进细胞增殖和集落形成。小鼠实验显示，宫颈癌细胞中miR-133b的上调强烈促进了体内肿瘤发生和小鼠肺的独立转移。数据表明，上调miR-133b可缩短宫颈癌的潜伏期。总之，这些发现表明miR-133b可能是宫颈癌早期发病的有效标志物。中华肿瘤杂志，2012,31 (1),467 - 475；doi: 10.1038 / onc.2011.561;2011年12月19日在线发布
We report that elevated microRNA-133b (miR-133b) acts as an oncogene in human cervical carcinoma to promote tumorigenesis and metastasis. In situ hybridization confirmed that miR-133b is localized in proliferating human cervical carcinoma cells with levels progressively elevating throughout advancing stages. Cellular studies showed that miR-133b enhances cell proliferation and colony formation by targeting mammalian sterile 20-like kinase 2 (MST2), cell division control protein 42 homolog (CDC42) and ras homolog gene family member A (RHOA), which subsequently results in activation of the tumorigenic protein kinase B alpha (AKT1) and mitogen-activated protein kinase (ERK1 and ERK2, here abbreviated as ERK) signaling pathways. Mouse experiments revealed that upregulation of miR-133b in cervical carcinoma cells strongly promotes both in vivo tumorigenesis and independent metastasis to the mouse lung. The data indicates that upregulation of miR-133b shortens the latency of cervical carcinoma. Together, these findings suggest that miR-133b could be a potent marker for the early onset of cervical carcinoma. Oncogene (2012) 31, 4067-4075; doi: 10.1038/onc.2011.561; published online 19 December 2011