LncRNA DGCR5 promotes lung adenocarcinoma (LUAD) progression via inhibiting hsa-mir-22-3p

被引:147
作者
Dong, Hui-Xing [1 ]
Wang, Ren [1 ]
Jin, Xiao-Yan [1 ]
Zeng, Jian [1 ]
Pan, Jing [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Tongren Hosp, Dept Resp Med, 1111 Xianxia Rd, Shanghai 200336, Peoples R China
关键词
apoptosis; DGCR5; hsa-mir-22-3p; LUAD; LONG NONCODING RNAS; EPITHELIAL-MESENCHYMAL TRANSITION; EPIGENETICALLY REPRESSING P21; HEPATOCELLULAR-CARCINOMA; REGULATING EXPRESSION; CANCER; METASTASIS; APOPTOSIS; PROLIFERATION; MALAT1;
D O I
10.1002/jcp.26215
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Long non-coding RNAs (lncRNAs) serve critical roles in the pathogenesis of various cancers, including lung adenocarcinoma (LUAD). Herein, in this study, we aimed to investigate the biological and clinical significance of lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) in LUAD. It was observed that DGCR5 was upregulated in LUAD tissues and LUAD cell lines. Inhibition of DGCR5 can prevent LUAD progression via playing anti-apoptosis roles. Both mRNA expression and protein levels of BCL-2 were increased by DGCR5 downregulation while reversely BAX was increased. Additionally, a novel microRNA target of DGCR5, hsa-mir-22-3p was identified through bioinformatics search and confirmed by dual-luciferase reporter system. Gain and loss-of-function studies were performed to verify whether DGCR5 exerts its biological functions through regulating hsa-mir-22-3p in vitro. Overexpression of DGCR5 was able to reverse the tumor inhibitory effect of hsa-mir-22-3p mimics. Furthermore, in vivo tests tumor xenografts were established to detect the function of DGCR5 in LUAD tumorigenesis. Downregulated DGCR5 expression was greatly associated with smaller tumor size, implying a favorable prognosis of LUAD patients. Taken these together, DGCR5 could be considered as a prognostic biomarker and therapeutic target in LUAD diagnosis and treatment.
引用
收藏
页码:4126 / 4136
页数:11
相关论文
共 49 条
[1]   Genome-wide interrogation reveals hundreds of long intergenic noncoding RNAs that associate with cardiometabolic traits [J].
Ballantyne, Rachel L. ;
Zhang, Xuan ;
Nunez, Sara ;
Xue, Chenyi ;
Zhao, Wei ;
Reed, Eric ;
Salaheen, Danish ;
Foulkes, Andrea S. ;
Li, Mingyao ;
Reilly, Muredach P. .
HUMAN MOLECULAR GENETICS, 2016, 25 (14) :3125-3141
[2]   Crosstalk between Long Noncoding RNAs and MicroRNAs in Health and Disease [J].
Bayoumi, Ahmed S. ;
Sayed, Amer ;
Broskova, Zuzana ;
Teoh, Jian-Peng ;
Wilson, James ;
Su, Huabo ;
Tang, Yao-Liang ;
Kim, Il-man .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2016, 17 (03)
[3]   Long Noncoding RNAs as Biomarkers in Cancer [J].
Bolha, Luka ;
Ravnik-Glavac, Metka ;
Glavac, Damjan .
DISEASE MARKERS, 2017, 2017
[4]   High expression of GPR116 indicates poor survival outcome and promotes tumor progression in colorectal carcinoma [J].
Yang, Li ;
Lin, Xiao-Lu ;
Liang, Wei ;
Fu, Seng-Wang ;
Lin, Wen-Feng ;
Tian, Xiao-Qing ;
Gao, Yun-Jie ;
Chen, Hao-Yan ;
Dai, Jun ;
Ge, Zhi-Zheng .
ONCOTARGET, 2017, 8 (29) :47943-47956
[5]   Overexpression of lncRNA HOXA11-AS promotes cell epithelial-mesenchymal transition by repressing miR-200b in non-small cell lung cancer [J].
Chen, Jian-Hui ;
Zhou, Li-Yang ;
Xu, Suo ;
Zheng, Yu-Long ;
Wan, Yu-Feng ;
Hu, Cheng-Ping .
CANCER CELL INTERNATIONAL, 2017, 17
[6]  
Cui JD, 2015, INT J CLIN EXP PATHO, V8, P12400
[7]   A Parsimonious Model for Gene Regulation by miRNAs [J].
Djuranovic, Sergej ;
Nahvi, Ali ;
Green, Rachel .
SCIENCE, 2011, 331 (6017) :550-553
[8]   Long non-coding RNAs in stem cells and cancer [J].
Eades, Gabriel ;
Zhang, Yong-Shu ;
Li, Qing-Lin ;
Xia, Ji-Xiang ;
Yao, Yuan ;
Zhou, Qun .
WORLD JOURNAL OF CLINICAL ONCOLOGY, 2014, 5 (02) :134-141
[9]   Oncocers: ceRNA-mediated cross-talk by sponging miRNAs in oncogenic pathways [J].
Ergun, Sercan ;
Oztuzcu, Serdar .
TUMOR BIOLOGY, 2015, 36 (05) :3129-3136
[10]   miR-22 promotes apoptosis of osteosarcoma cells via inducing cell cycle arrest [J].
Gai, Pengzhou ;
Sun, Hongliang ;
Wang, Guangda ;
Xu, Qiang ;
Qi, Xiaojun ;
Zhang, Zuofu ;
Jiang, Lei .
ONCOLOGY LETTERS, 2017, 13 (04) :2354-2358