MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer.
MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer.
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DOI：
10.1016/j.ccr.2014.03.006
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发表时间：
2014-04-14
期刊：
影响因子：
50.3
通讯作者：
Croce CM
中科院分区：
文献类型：
--
作者：
Valeri N;Braconi C;Gasparini P;Murgia C;Lampis A;Paulus-Hock V;Hart JR;Ueno L;Grivennikov SI;Lovat F;Paone A;Cascione L;Sumani KM;Veronese A;Fabbri M;Carasi S;Alder H;Lanza G;Gafa' R;Moyer MP;Ridgway RA;Cordero J;Nuovo GJ;Frankel WL;Rugge M;Fassan M;Groden J;Vogt PK;Karin M;Sansom OJ;Croce CM
microRNA失调在人类结直肠癌（CRC）中很常见，但对于它是否代表旁观者事件或实际上驱动体内肿瘤进展知之甚少。我们发现，miR-135 b过表达在小鼠和人类中由APC丢失、PTEN/PI 3 K通路失调和SRC过表达触发，并促进肿瘤转化和进展。我们发现，miR-135 b上调在散发性和炎症性肠病相关的人类CRC中很常见，并与肿瘤分期和不良临床结局相关。在CRC小鼠模型中抑制miR-135 b通过控制参与增殖、侵袭和凋亡的基因来减少肿瘤生长。我们确定miR-135 b是致癌途径的关键下游效应子，也是CRC治疗的潜在靶点。miR-135 b在小鼠和人结直肠癌中过表达miR-135 b过表达与不良临床结果相关miR-135 b激活由结直肠癌中的致癌途径触发miR-135 b代表结直肠癌的治疗靶点Valeri et al.将miR-135 b鉴定为参与转化和结直肠癌（CRC）进展的关键致癌途径效应物。人CRC中miR-135 b的上调与不良临床结局相关。miR-135 b靶向多种肿瘤抑制基因，是CRC治疗的潜在靶点。
MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment. miR-135b is overexpressed in mouse and human colorectal cancer miR-135b overexpression is associated with poor clinical outcome miR-135b activation is triggered by oncogenic pathways in colorectal cancer miR-135b represents a therapeutic target for colorectal cancer Valeri et al. identify miR-135b as a key oncogenic pathway effector involved in transformation and colorectal cancer (CRC) progression. Upregulation of miR-135b in human CRCs correlates with poor clinical outcome. miR-135b targets several tumor suppressor genes and is a potential target for CRC therapy.
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影响因子：
30.8
作者：
Marsh, Victoria;Winton, Douglas J.;Clarke, Alan R.
通讯作者：
Clarke, Alan R.
影响因子：
4.6
作者：
Borinstein, Scott C.;Conerly, Melissa;Dzieciatkowski, Slavomir;Biswas, Swati;Washington, M. Kay;Trobridge, Patty;Henikoff, Steve;Grady, William M.
通讯作者：
Grady, William M.
影响因子：
6.2
作者：
Aust, DE;Terdiman, JP;Waldman, FM
通讯作者：
Waldman, FM
影响因子：
64.5
作者：
Lewis, BP;Shih, IH;Burge, CB
通讯作者：
Burge, CB
DOI：
10.1073/pnas.93.15.7950
发表时间：
1996-07-23
影响因子：
11.1
作者：
Morin, PJ;Vogelstein, B;Kinzler, KW
通讯作者：
Kinzler, KW