LncRNA TTN-AS1 promotes migration, invasion, and epithelial mesenchymal transition of lung adenocarcinoma via sponging miR-142-5p to regulate CDK5

被引：104
作者：
Jia, Yunlong [1 ,2 ]
Duan, Yuqing [1 ,2 ]
Liu, Tianxu [1 ,2 ]
Wang, Xuexiao [1 ,2 ]
Lv, Wei [1 ,2 ]
Wang, Mengjie [1 ,2 ]
Wang, Jiali [1 ,2 ]
Liu, Lihua [1 ,2 ]
机构：
[1] Hebei Med Univ, Hosp 4, Dept Tumor Immunotherapy, Shijiazhuang 050035, Hebei, Peoples R China
[2] Hebei Canc Inst, Shijiazhuang 050035, Hebei, Peoples R China
来源：
CELL DEATH & DISEASE | 2019年 / 10卷 / 8期
基金：
中国国家自然科学基金;
关键词：
LONG NONCODING RNA; C-MYC; CANCER; EXPRESSION; ACTIVATION; GROWTH; GENE; EMT;
D O I：
10.1038/s41419-019-1811-y
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Emerging evidence suggests that long noncoding RNA (lncRNA) plays pivotal roles in regulating various biological process in human cancers. Titin-antisense RNA1 (TTN-AS1) has been regarded as a tumor promoting lncRNA in numerous cancers. However, the clinical significance and biological function of TTN-AS1 in lung adenocarcinoma (LUAD) remain unclear. In the present study, we revealed that the expression of TTN-AS1 was upregulated in LUAD tissues and cell lines. High TTN-AS1 expression was associated with TNM stage and lymph node metastasis of LUAD patients. In addition, high expression of TTN-AS1 was correlated with poor postoperative prognosis of LUAD patients. Knockdown of TTN-AS1 significantly inhibited the growth, proliferation, migration, and invasion ability of LUAD cells in vitro. Then, by using bioinformation analysis and luciferase reporter experiment, we identified that TTN-AS1 could function as a competing endogenous RNA (ceRNA) by sponging miR-142-5p to regulate the expression of cyclin-dependent kinase 5 (CDK5) in LUAD. Since CDK5 is a key regulator in the process of epithelial mesenchymal transition (EMT), we detected the expression of EMT-related proteins, consequently, EMT was suppressed by knockdown of TTN-AS1 while this phenomenon was rescued by miR-142-5p inhibitor. Taken above, our study revealed that TTN-AS1 played an important role in LUAD progression. TTN-AS1/miR-142-5p/CDK5 regulatory axis may serve as a novel therapeutic target in the treatment of LUAD.
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页数：13
相关论文
共 40 条
[1]   Long Noncoding RNAs: Cellular Address Codes in Development and Disease [J].
Batista, Pedro J. ;
Chang, Howard Y. .
CELL, 2013, 152 (06) :1298-1307
[2]   LncRNA-FEZFl-AS1 Promotes Tumor Proliferation and Metastasis in Colorectal Cancer by Regulating PKM2 Signaling [J].
Bian, Zehua ;
Zhang, Jiwei ;
Li, Min ;
Feng, Yuyang ;
Wang, Xue ;
Zhang, Jia ;
Yao, Surui ;
Jin, Guoying ;
Du, Jun ;
Han, Weifeng ;
Yin, Yuan ;
Huang, Shenglin ;
Fei, Bojian ;
Zou, Jian ;
Huang, Zhaohui .
CLINICAL CANCER RESEARCH, 2018, 24 (19) :4808-4819
[3]   A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA [J].
Cesana, Marcella ;
Cacchiarelli, Davide ;
Legnini, Ivano ;
Santini, Tiziana ;
Sthandier, Olga ;
Chinappi, Mauro ;
Tramontano, Anna ;
Bozzoni, Irene .
CELL, 2011, 147 (02) :358-369
[4]   Long non-coding RNA TTN-AS1 promotes cell growth and metastasis in cervical cancer via miR-573/E2F3 [J].
Chen, Ping ;
Wang, Rui ;
Yue, Qingfen ;
Hao, Mengmeng .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2018, 503 (04) :2956-2962
[5]   miR-142-5p suppresses proliferation and promotes apoptosis of human osteosarcoma cell line, HOS, by targeting PLA2G16 through the ERK1/2 signaling pathway [J].
Cheng, Deliang ;
Li, Jiageng ;
Zhang, Lijun ;
Hu, Leiming .
ONCOLOGY LETTERS, 2019, 17 (01) :1363-1371
[6]   Long non-coding RNA TTN-AS1 facilitates tumorigenesis of papillary thyroid cancer through modulating the miR-153-3p/ZNRF2 axis [J].
Cui, Zhenghui ;
Luo, Zhiyan ;
Lin, Zimei ;
Shi, Liuhong ;
Hong, Yurong ;
Yan, Caoxin .
JOURNAL OF GENE MEDICINE, 2019, 21 (05)
[7]   Regulatory networks defining EMT during cancer initiation and progression [J].
De Craene, Bram ;
Berx, Geert .
NATURE REVIEWS CANCER, 2013, 13 (02) :97-110
[8]   LncRNA TTN-AS1 contributes to gastric cancer progression by acting as a competing endogenous RNA of miR-376b-3p [J].
Dong, M. M. ;
Peng, S. J. ;
Yuan, Y. N. ;
Luo, H. P. .
NEOPLASMA, 2019, 66 (04) :564-575
[9]   Cdk5 disruption attenuates tumor PD-L1 expression and promotes antitumor immunity [J].
Dorand, R. Dixon ;
Nthale, Joseph ;
Myers, Jay T. ;
Barkauskas, Deborah S. ;
Avril, Stefanie ;
Chirieleison, Steven M. ;
Pareek, Tej K. ;
Abbott, Derek W. ;
Stearns, Duncan S. ;
Letterio, John J. ;
Huang, Alex Y. ;
Petrosiute, Agne .
SCIENCE, 2016, 353 (6297) :399-403
[10]   Analysis of the Cancer Genome Atlas Data Reveals Novel Putative ncRNAs Targets in Hepatocellular Carcinoma [J].
Falcon, Tiago ;
Freitas, Martiela ;
Mello, Ana Carolina ;
Coutinho, Laura ;
Alvares-da-Silva, Mario R. ;
Matte, Ursula .
BIOMED RESEARCH INTERNATIONAL, 2018, 2018
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