期刊
CLINICAL CANCER RESEARCH
卷 23, 期 17, 页码 5255-5266出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-17-0023
关键词
-
类别
资金
- Erwin-Schroedinger Scholarship of the Austrian Science Funds [J3389-B23]
- Verein fur Krebskranke of the Medical University of Graz
- fund of the Oesterreichische National bank [14869]
- Styrian Krebshilfe
- Oesterreichische National bank [15400]
- START grant from the Medical University of Graz
- Hans und Blanca Moser Foundation for Early Stage Cancer Researcher
- Czech Ministry of Health [IGA NT/13860-4/2012]
- project CEITEC (Central European Institute of Technology) [CZ.1.05/1.1.00/02.0068]
- project BBMRI CZ [LM2010004]
- NIH/NCI grants [1UH2TR00943-01, 1R01 CA182905-01]
- UT MD Anderson Cancer Center SPORE in Melanoma grant from NCI [P50 CA093459]
- Aim at Melanoma Foundation
- Miriam and Jim Mulva research funds
- UT MD Anderson Cancer Center Brain SPORE [2P50CA127001]
- Developmental Research award from Leukemia SPORE
- CLL Moonshot Flagship project
- a Knowledge GAP MDACC grant
- Owens Foundation grant
- Estate of C. G. Johnson Jr
- National Institute for Health Research [CL-2015-26-003, ACF-2007-26-004] Funding Source: researchfish
Purpose: miR-196b-5p has been previously implicated in malignant transformation; however, its role in colorectal cancer has not been fully explored. In this study, we examine the clinical and biological relevance of miR-196b-5p, and the molecular pathways regulated by miR-196b-5p in colorectal cancer. Experimental Design: miR-196b-5p expression was quantitated by qRT-PCR in 2 independent cohorts composed of 292 patients with colorectal cancer in total, to explore its biomarker potential. Transient and stable gain-and loss-of-function experiments were conducted in a panel of colorectal cancer cell lines and mice, to evaluate the impact of miR-196b-5p on proliferation, chemosensitivity, migration/invasion, and metastases formation in vitro and in vivo. The molecular pathways influenced by miR196b-5p were characterized using whole transcriptome profiling, in silico target prediction tools, luciferase interaction assays, and phenocopy/rescue gene knockdown experiments. Results: Low miR-196b-5p expression was significantly associated with metastases and poor outcomes in 2 independent colorectal cancer patient cohorts (P < 0.05, log-rank test). miR-196b-5p inhibition led to significantly increased colorectal cancer cell migration/invasion and metastases formation in mice, whereas ectopic overexpression showed the opposite phenotype. Molecular profiling and target confirmation identified an interaction between miR-196b-5p and HOXB7 and GALNT5, which in turn regulated colorectal cancer cell migration. Conclusions: The association of low levels of miR-196b-5p and poor prognosis in patients with colorectal cancer can be explained by its influence on cancer cell migration and metastases formation. miR-196b-5p has an impact on colorectal cancer progression pathways through direct interaction with genes involved in cancer cell migration. (C) 2017 AACR.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据