Circular RNA hsa_circ_0000326 acts as a miR-338-3p sponge to facilitate lung adenocarcinoma progression

被引:63
|
作者
Xu, Yuzhu [1 ,2 ]
Yu, Jun [3 ]
Huang, Zhenli [1 ]
Fu, Bohua [1 ]
Tao, Yu [1 ]
Qi, Xuefei [1 ]
Mou, Yong [1 ]
Hu, Yinan [1 ]
Wang, Yi [1 ]
Cao, Yong [1 ]
Jiang, Dingsheng [4 ]
Xie, Jungang [1 ]
Xu, Yongjian [1 ]
Zhao, Jianping [1 ]
Xiong, Weining [1 ,5 ]
机构
[1] Huazhong Univ Sci & Technol, Dept Resp & Crit Care Med,Tongji Med Coll, Wuhan Clin Med Res Ctr Chron Airway Med,Tongji Ho, NHC Key Lab Pulm Dis,Key Cite Natl Clin Res Ctr R, 1095 Jiefang Ave, Wuhan 430030, Peoples R China
[2] Zhuzhou Cent Hosp, Dept Resp, Zhuzhou, Peoples R China
[3] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Thorac Surg, Tongji Med Coll, Wuhan, Peoples R China
[4] Huazhong Univ Sci & Technol, Tongji Hosp, Div Cardiothorac & Vasc Surg, Tongji Med Coll, Wuhan, Peoples R China
[5] Shanghai Jiao Tong Univ, Sch Med, Dept Resp Med, Shanghai Ninth Peoples Hosp, 639 Zhizaoju Lu, Shanghai 200011, Peoples R China
基金
中国国家自然科学基金;
关键词
CANCER PROGRESSION; BIOMARKER; CELLS; PROLIFERATION; CARCINOMA;
D O I
10.1186/s13046-020-01556-4
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Circular RNAs (circRNAs) are a novel class of noncoding RNAs that regulate gene expression at the transcriptional or posttranscriptional level. According to recent studies, circRNAs are involved in the pathogenesis of cancer, but the roles of circRNAs in lung adenocarcinoma are largely unknown. Methods In this study, we identified a novel upregulated circRNA, hsa_circ_0000326, in human lung adenocarcinoma tissues using microarray analysis and qRT-PCR. We then explored the biological role of hsa_circ_0000326 using gain- and loss-of-function assays in adenocarcinoma cells. Bioinformatics databases were used to screen for potential target miRNAs and the luciferase reporter assays and RNA-FISH further validated the interaction. Downstream protein was detected by western blot. Finally, we established xenografts in nude mice to assess the function of hsa_circ_0000326 in vivo. Results We found that high expression of hsa_circ_0000326 was correlated with tumor size, regional lymph node status and differentiation in human lung adenocarcinoma. Additionally, we conducted gain- and loss-of-function assays and found that hsa_circ_0000326 acted as a positive regulator of cell proliferation and migration and a negative regulator of apoptosis. Mechanistic studies showed that hsa_circ_0000326 acted as a miR-338-3p sponge and altered the function of miR-338-3p, which in turn upregulated the expression of the downstream target RAB14 and affected the proliferation, migration and apoptosis of lung adenocarcinoma cells. Conclusions Collectively, our study results reveal crucial roles for hsa_circ_0000326 in the proliferation, migration and apoptosis of lung adenocarcinoma cells and suggest that hsa_circ_0000326 may represent a potential therapeutic target in patients with lung adenocarcinoma.
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页数:14
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