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.

引用

页数：13

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