血管生成
癌症研究
癌症
下调和上调
癌基因
生物
癌细胞
体内
结直肠癌
细胞周期
基因
生物化学
遗传学
生物技术
作者
Junling Zhang,Xiaocong Pang,Lili Lei,Jixin Zhang,Xiaoqian Zhang,Ziyi Chen,Jing Zhu,Yong Jiang,Guowei Chen,Yingchao Wu,Tao Wu,Yisheng Pan,Yucun Liu,Yimin Cui,Xin Wang
出处
期刊:Aging
[Impact Journals, LLC]
日期:2022-05-10
卷期号:14 (9): 4137-4157
被引量:1
标识
DOI:10.18632/aging.204078
摘要
We previously identified a novel lncRNA, CRART16, that could induce cetuximab resistance in colorectal cancer cells. This study explored the relationship of CRART16 expression to gastric cancer progression and the molecular mechanisms involved.We evaluated CRART16 expression in gastric cancer tissues and adjacent normal tissues from the TCGA database and our hospital. Besides, we assessed its relationship with the overall survival (OS) of patients with gastric cancer. The effects of CRART16 on gastric cancer angiogenesis were determined by endothelial tube formation assay, spheroid sprouting assay, HUVEC invasion assay, and chick embryo chorioallantoic membrane (CAM) assay. The involvement of the lncRNA CRART16/miR-122-5p/FOS axis was analyzed by western blotting and dual-luciferase reporter assay. The functions of CRART16 were confirmed in xenograft mouse models.We found that CRART16 was substantially overexpressed in gastric cancer tissues compared with normal tissues, based on the TCGA database and our clinical samples. High expression of CRART16 correlated with more advanced tumor stages and poor prognosis. Overexpression of CRART16 in gastric cancer cells promoted proliferation, colony formation, angiogenesis, and bevacizumab resistance in vitro, and it promoted tumor growth and angiogenesis in vivo, and vice versa. CRART16 was found to downregulate miR-122-5p by acting as a sponge, upregulating the target oncogene FOS. Afterward, the increased FOS expression led to the upregulation of VEGFD.Our findings demonstrate that CRART16 promotes angiogenesis in vitro and in vivo, and CRART16 is a prognostic marker and therapeutic target in gastric cancer.
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