|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|
|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|
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.
|项目编号||7122183 ; 81372746|
|资助机构||Beijing Natural Science Foundation ; National Natural Science Foundation|
|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
|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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