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学科主题: 基础医学
题名:
Let-7c functions as a metastasis suppressor by targeting MMP11 and PBX3 in colorectal cancer
作者: Han, Hai-Bo1; Gu, Jin2; Zuo, Hui-Jing1; Chen, Zhi-Guo2; Zhao, Wei1; Li, Ming2; Ji, Deng-Bo2; Lu, You-Yong3; Zhang, Zhi-Qian1
关键词: microRNA ; metastasis ; colorectal cancer ; let-7c ; MMP11 ; PBX3 ; K-RAS
刊名: JOURNAL OF PATHOLOGY
发表日期: 2012-02-01
DOI: 10.1002/path.3014
卷: 226, 期:3, 页:544-555
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology ; Pathology
研究领域[WOS]: Oncology ; Pathology
关键词[WOS]: REAL-TIME PCR ; MATRIX-METALLOPROTEINASE ; LUNG-CANCER ; MICRORNA EXPRESSION ; INDUCED APOPTOSIS ; PROSTATE-CANCER ; GASTRIC-CANCER ; CELL-LINES ; IN-VIVO ; RT-PCR
英文摘要:

Accumulating evidence shows that microRNAs, functioning as either oncogenes or tumour suppressors by negatively regulating downstream target genes that are actively involved in tumour initiation and progression, may be promising biomarkers and therapy targets. Data mining through a microRNA chip database indicated that let-7c may be associated with tumour metastasis. Here, we confirmed that down-regulation of let-7c in primary cancer tissues was significantly associated with metastases, advanced TNM stages and poor survival of colorectal cancer patients. Moreover, ectopic expression of let-7c in a highly metastatic Lovo cell line remarkably suppressed cell migration and invasion in vitro by the down-regulation of K-RAS, MMP11 and PBX3, as well as tumour growth and metastases in vivo, whereas inhibition of let-7c in low-metastatic HT29 cells increased cell motility and invasion by the enhanced gene expression of K-RAS, MMP11 and PBX3. Interestingly, the luciferase reporters′ activities with the 3′-UTRs of K-RAS, MMP11 and PBX3 were inhibited significantly by let-7c. Importantly, rescue experiments involving the over-expression of these genes without their 3′-UTRs completely reversed the effects of let-7c on tumour metastasis, both in vitro and in vivo. Finally, the levels of let-7c were inversely correlated with those of MMP11 and PBX3, but not with those of K-RAS. Taken together, these results demonstrate that let-7c, apart from its tumour growth suppression role, also functions as a tumour metastasis suppressor in colorectal cancer by directly destabilizing the mRNAs of MMP11 and PBX3 at least. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

语种: 英语
所属项目编号: 30971494 ; 81071733 ; 2010CB529402 ; 2011-2-24
项目资助者: National Natural Science Foundation ; National Basic Research Programme of China (973 Programme) ; Beijing Municipal Outstanding Talents Training Funds in Health Sciences
WOS记录号: WOS:000299158400016
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65208
Appears in Collections:基础医学院_细胞生物学系_期刊论文

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作者单位: 1.Peking Univ, Dept Cell Biol, Sch Oncol,Beijing Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100142, Peoples R China
2.Peking Univ, Dept Colorectal Surg, Sch Oncol, Beijing Canc Hosp & Inst, Beijing 100142, Peoples R China
3.Peking Univ, Mol Oncol Lab, Sch Oncol, Beijing Canc Hosp & Inst, Beijing 100142, Peoples R China

Recommended Citation:
Han, Hai-Bo,Gu, Jin,Zuo, Hui-Jing,et al. Let-7c functions as a metastasis suppressor by targeting MMP11 and PBX3 in colorectal cancer[J]. JOURNAL OF PATHOLOGY,2012,226(3):544-555.
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