LncRNA TDRG1 enhances tumorigenicity in endometrial carcinoma by binding and targeting VEGF-A protein

• Published in: Biochimica et biophysica acta. Molecular basis of disease 2018-09, Vol.1864 (9), p.3013-3021
• Main Authors: Chen, Shuo, Wang, Li-li, Sun, Kai-xuan, Liu, Yao, Guan, Xue, Zong, Zhi-hong, Zhao, Yang
• Format: Article
• Language: English
• Subjects: Aged; Animals; Carcinogenesis - genetics; Cell Line, Tumor; Cell Proliferation - genetics; Endometrial carcinoma; Endometrial Neoplasms - genetics; Endometrial Neoplasms - pathology; Endometrial Neoplasms - surgery; Endometrium - pathology; Endometrium - surgery; Female; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; LncRNA TDRG1; Mice; Mice, Nude; Middle Aged; Neoplasm Invasiveness - genetics; Proteins - genetics; Proteins - metabolism; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Small Interfering - metabolism; Tumorigenesis and progression; Up-Regulation; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; VEGF-A; Xenograft Model Antitumor Assays
• ISSN: 0925-4439; 1879-260X
• DOI: 10.1016/j.bbadis.2018.06.013

Endometrial carcinoma is one of the most frequently diagnosed cancers in females. Long non-coding RNAs (lncRNAs) have been associated with cancer; its role in endometrial carcinoma is an emerging area of research. In this article, lncRNA TDRG1 expression in human endometrial carcinoma tissues and normal endometrial tissues was quantified by qRT-PCR. LncRNA TDRG1 was overexpressed or knocked-down in neither HEC-1B nor Ishikawa endometrial carcinoma cells, respectively, to assess cellular phenotype and expression of related molecules. Our results showed that lncRNA TDRG1 was significantly overexpressed in endometrial carcinoma tissues. Overexpression of lncRNA TDRG1 promoted endometrial carcinoma cell viability, invasion and migratory ability, inhibited apoptosis, and upregulated VEGF-A, PI3K, Bcl-2, MMP2 and survivin; knockdown of lncRNA TDRG1 had the opposite effects. LncRNA TDRG1 overexpression increased tumorigenicity in vivo and was associated with the upregulation of VEGF-A. RNA binding protein immunoprecipitation (RIP) assays confirmed that lncRNA TDRG1 directly binds to VEGF-A protein. Furthermore, knockdown of VEGFA in lncRNA TDRG1-overexpressing endometrial carcinoma cells reversed the effects of lncRNA TDRG1 on cell proliferation, invasion, migration and apoptosis. In conclusion, lncRNA TDRG1 may promote endometrial carcinoma cell proliferation and invasion by positively targeting VEGF-A and modulating relative genes. •LncRNA TDRG1 was significantly overexpressed in endometrial carcinoma (EC) tissues.•LncRNA TDRG1 promoted EC cell viability, invasion and migration, inhibited cell apoptosis.•LncRNA TDRG1 may promote EC cell proliferation and invasion by positively targeting VEGF-A and modulating relevant genes.