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Overexpressed long noncoding RNA TUG1 affects the cell cycle, proliferation, and apoptosis of pancreatic cancer partly through suppressing RND3 and MT2A
- Source :
- OncoTargets and Therapy. 12:1043-1057
- Publication Year :
- 2019
- Publisher :
- Informa UK Limited, 2019.
-
Abstract
- Background Long noncoding RNAs (lncRNAs) are involved in various human diseases, including cancers. However, their mechanisms remain undocumented. We investigated alterations in lncRNA that may be related to pancreatic cancer (PC) through analysis of microarray data. Methods In the present study, quantitative real-time PCR analysis was used to examine the expression of taurine upregulated 1 (TUG1) in PC tissue samples and PC cell lines. In PC cell lines, MTT assays, colony formation assays, and flow cytometry were used to investigate the effects of TUG1 on proliferation, cell cycle regulation, and apoptosis. Moreover, we established a xenograft model to assess the effect of TUG1 on tumor growth in vivo. The molecular mechanism of potential target genes was detected through nuclear separation experiments, RNA immunoprecipitation (RIP), chromatin immunoprecipitation assays (ChIP), and other experimental methods. Results The findings suggest that the abnormally high expression of TUG1 in PC tissues was associated with tumor size and pathological stage. Knockdown of TUG1 blocked the cell cycle and accelerated apoptosis, thereby inhibiting the proliferation of PC cells. In addition, RIP experiments showed that TUG1 can recruit enhancer of zeste homolog 2 (EZH2) to the promoter regions of Rho family GTPase 3 (RND3) and metallothionein 2A (MT2A) and inhibit their expression at the transcriptional level. Furthermore, ChIP experiments demonstrated that EZH2 could bind to the promoter regions of RND3 and MT2A. The knockdown of TUG1 reduced this binding capacity. Conclusion In conclusion, our data suggest that TUG1 may regulate the expression of PC-associated tumor suppressor genes at the transcriptional level and these may become potential targets for the diagnosis and treatment of PC.
- Subjects :
- 0301 basic medicine
Gene knockdown
Chemistry
Microarray analysis techniques
EZH2
Cell cycle
Non-coding RNA
Long non-coding RNA
Cell biology
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Oncology
Apoptosis
030220 oncology & carcinogenesis
Pharmacology (medical)
Chromatin immunoprecipitation
Subjects
Details
- ISSN :
- 11786930
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- OncoTargets and Therapy
- Accession number :
- edsair.doi...........6f89c125f76d7ebf2ec1364e6c5297c4