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Let-7d suppresses growth, metastasis, and tumor macrophage infiltration in renal cell carcinoma by targeting COL3A1 and CCL7
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
2014-09-06
DOI10.1186/1476-4598-13-206
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
WOS记录号WOS:000342018600001
项目编号7122183 ; 81372746
资助机构Beijing Natural Science Foundation ; National Natural Science Foundation
引用统计
被引频次:32[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/400002259/57996
专题北京大学第一临床医学院_泌尿外科
北京大学基础医学院
北京大学第二临床医学院_放射科
北京大学口腔医学院_中心实验室
北京大学临床肿瘤学院_603课题组
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
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GB/T 7714
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.
APA Su, Boxing.,Zhao, Wei.,Shi, Bentao.,Zhang, Zhongyuan.,Yu, Xi.,...&Zhou, Liqun.(2014).Let-7d suppresses growth, metastasis, and tumor macrophage infiltration in renal cell carcinoma by targeting COL3A1 and CCL7.MOLECULAR CANCER,13.
MLA Su, Boxing,et al."Let-7d suppresses growth, metastasis, and tumor macrophage infiltration in renal cell carcinoma by targeting COL3A1 and CCL7".MOLECULAR CANCER 13(2014).
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