北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学第一临床医学院  > 泌尿外科  > 期刊论文
学科主题: 临床医学
题名:
Let-7d suppresses growth, metastasis, and tumor macrophage infiltration in renal cell carcinoma by targeting COL3A1 and CCL7
作者: Su, Boxing1,2,3; Zhao, Wei4; Shi, Bentao5; Zhang, Zhongyuan1,2,3; Yu, Xi1,2,3; Xie, Feng1,2,3; Guo, Zhongqiang1,2,3; Zhang, Xiaoyu1,2,3; Liu, Jin1,2,3; Shen, Qi2,6; Wang, Jinghua2,6; Li, Xuesong1,2,3; Zhang, Zhiqian4; Zhou, Liqun1,2,3
关键词: Renal cell carcinoma ; MicroRNA ; Let-7
刊名: MOLECULAR CANCER
发表日期: 2014-09-06
DOI: 10.1186/1476-4598-13-206
卷: 13
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Oncology
研究领域[WOS]: Biochemistry & Molecular Biology ; Oncology
关键词[WOS]: LOOP RT-PCR ; HEPATOCELLULAR-CARCINOMA ; LUNG ADENOCARCINOMA ; GENE-EXPRESSION ; POOR-PROGNOSIS ; CANCER ; MICRORNAS ; DIFFERENTIATION ; INVASION ; FAMILY
英文摘要:

Background: MicroRNAs are endogenous small noncoding RNAs that are functionally involved in numerous critical cellular processes including tumorigenesis. Data mining using a microRNA array database suggested that let-7d microRNA may be associated with renal cell carcinoma (RCC) malignant progression. Here, we performed further analyses to determine whether let-7d is functionally linked to RCC malignancy.

Methods: Quantitative real-time PCR was used to determine the level of mature let-7d in RCC clinical specimens and its correlation with clinicopathological data. Immunohistochemical staining was conducted to characterize the stroma of RCC. Let-7d overexpressing RCC cell lines combined with mouse models bearing cell-derived xenografts and patient-derived xenografts were used to assess the functional role of let-7d in vitro and in vivo.

Results: Downregulation of let-7d in clinical RCC samples was associated with advanced tumor grade and T stage and increased vascular invasion. An inverse relationship between let-7d expression and macrophage infiltration was found in clinical RCC samples. Functional studies indicated that ectopic expression of let-7d significantly inhibited RCC cell proliferation, migration, and peripheral blood monocyte (PBMC) recruitment in vitro, as well as tumor growth, metastasis, and tumor macrophage infiltration in vivo. In silico analysis and subsequent experimental validation confirmed collagen, type III, alpha 1 (COL3A1) and C-C subfamily chemokine member CCL7 as direct let-7d target genes. The addition of COL3A1 and CCL7 counteracted the inhibitory effects of let-7d on RCC cell proliferation, migration, and PBMC recruitment. The inhibition of let-7d increased cell proliferation, migration, and PBMC recruitment by the enhanced expression of COL3A1 and CCL7 genes in vitro. The mRNA levels of COL3A1 and CCL7 were inversely correlated with let-7d level in RCC clinical specimens.

Conclusions: These results suggest that let-7d may suppress RCC growth, metastasis, and tumor macrophage infiltration at least partially through targeting COL3A1 and CCL7.

语种: 英语
所属项目编号: 7122183 ; 81372746
项目资助者: Beijing Natural Science Foundation ; National Natural Science Foundation
WOS记录号: WOS:000342018600001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57996
Appears in Collections:北京大学第一临床医学院_泌尿外科_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Natl Urol Canc Ctr, Beijing 100034, Peoples R China
2.Peking Univ, Hosp 1, Dept Urol, Beijing 100034, Peoples R China
3.Peking Univ, Inst Urol, Beijing 100034, Peoples R China
4.Peking Univ, Sch Oncol, Beijing Canc Hosp & Inst, Dept Cell Biol, Beijing 100142, Peoples R China
5.Peking Univ, Shenzhen Hosp, Dept Urol, Shenzhen 518036, Guangdong, Peoples R China
6.Peking Univ, Hosp 1, Dept Urol Pathol, Beijing 100034, Peoples R China

Recommended Citation:
Su, Boxing,Zhao, Wei,Shi, Bentao,et al. Let-7d suppresses growth, metastasis, and tumor macrophage infiltration in renal cell carcinoma by targeting COL3A1 and CCL7[J]. MOLECULAR CANCER,2014,13.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Su, Boxing]'s Articles
[Zhao, Wei]'s Articles
[Shi, Bentao]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Su, Boxing]‘s Articles
[Zhao, Wei]‘s Articles
[Shi, Bentao]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace