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学科主题基础医学
Let-7c functions as a metastasis suppressor by targeting MMP11 and PBX3 in colorectal cancer
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
2012-02-01
DOI10.1002/path.3014
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
WOS记录号WOS:000299158400016
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被引频次:69[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/65208
专题北京大学基础医学院_细胞生物学系
北京大学临床肿瘤学院_603课题组
北京大学临床肿瘤学院_结直肠肿瘤外科
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
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GB/T 7714
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.
APA Han, Hai-Bo.,Gu, Jin.,Zuo, Hui-Jing.,Chen, Zhi-Guo.,Zhao, Wei.,...&Zhang, Zhi-Qian.(2012).Let-7c functions as a metastasis suppressor by targeting MMP11 and PBX3 in colorectal cancer.JOURNAL OF PATHOLOGY,226(3),544-555.
MLA Han, Hai-Bo,et al."Let-7c functions as a metastasis suppressor by targeting MMP11 and PBX3 in colorectal cancer".JOURNAL OF PATHOLOGY 226.3(2012):544-555.
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