Linc00462 promotes pancreatic cancer invasiveness through the miR-665/TGFBR1-TGFBR2/SMAD2/3 pathway

被引:85
作者
Zhou, Bin [1 ]
Guo, Weidong [1 ]
Sun, Chuandong [1 ]
Zhang, Bingyuan [1 ]
Zheng, Fang [2 ]
机构
[1] Qingdao Univ, Dept Hepatopacreatobiliary, Affiliated Hosp, Qingdao 266003, Peoples R China
[2] Tianjin Tradit Med Univ, Sch Integrat Med, Tianjin 300193, Peoples R China
来源
CELL DEATH & DISEASE | 2018年 / 9卷
基金
中国国家自然科学基金;
关键词
LONG NONCODING RNA; EPITHELIAL-MESENCHYMAL TRANSITION; COMPETING ENDOGENOUS RNA; EMT; PROLIFERATION; EXPRESSION; INVASION; MICRORNA-665; METASTASIS; MECHANISMS;
D O I
10.1038/s41419-018-0724-5
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Emerging evidence has identified that long non-coding RNAs (lncRNAs) may play an important role in the pathogenesis of many cancers, pancreatic cancer (PC) included. However, the role of linc00462 in PC remains unclear. The aim of our present study was to investigate the potential functions of linc00462 in PC and to identify the underlying mechanisms of action. CCK8 assay, transwell assay, cell cycle assay, cell apoptosis assay, EdU assay, western blot assay, cell adhesion assay, HE staining, IF staining, ELISA assay, vivo growth and metastasis assay, and colony formation assay were performed. We demonstrated that OSM mediated up-regulation of linc00462 promoted cell proliferation by accelerating cell cycle process and inhibiting cell apoptosis and adhesion in vitro, enhanced cell migration and invasion by accelerating EMT process, promoted tumor growth and matastasis in vivo and was associated with large tumor size, poor tumor differentiation, TNM stage and distant metastasis in patients of PC. In addition, we demonstrated that linc00462 was a target of miR-665. Linc00462 overexpression enhanced the expression levels of TGFBR1 and TGFBR2, and thus activated the SMAD2/3 pathway in PC cells. In conclusion, linc00462/miR-665/TGFBR1/2 regulatory network may shed light on tumorigenesis in PC.
引用
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页数:15
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