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MiR-539 functions as a tumor suppressor in pancreatic cancer by targeting TWIST1
Haibo Yu1, Ganglong Gao2, Jing Cai1
1Department of Hepatobiliary Surgery, Wenzhou Central Hospital, The Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China.
Abstract:
The dysregulation of microRNA (miRNA) expression has been highlighted in a variety of human malignant conditions with reports implicating a critical role in the process of tumor growth. The role of miR-539 in pancreatic cancer (PC) is yet to be fully elucidated, hence the aim of the current study was to investigate the effect of miR-539 expression in relation to a cohort of 52 PC specimens. The application of a real-time quantitative polymerase chain reaction (qRT-PCR) revealed a significantly down-regulated miR-539 level, which was accompanied by an increased TWIST1 expression in PC when compared with the controls. The in vitro experiment results demonstrated that the endogenic mimic of miR-539 significantly suppressed the growth of the xenograft tumors in PANC-1 cells, when compared to the delivery of the control miRNA and blank control. Meanwhile, the key epithelial-mesenchymal transition (EMT) inducer, TWIST1 was verified as a direct target gene of miR-539 through the application of a luciferase reporter assay. In conclusion, the results of the current study present evidence emphasizing the significance of the interactions between miR-539 and TWIST1 in the development of and progression of PC, highlighting its potential as a therapeutic target in the treatment of PC patients.
Insights
MicroRNA 539 (miR-539) is downregulated in pancreatic cancer (PC), promoting tumor growth. Restoring miR-539 inhibits PC progression by targeting TWIST1, suggesting therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA (miRNA) dysregulation is implicated in various human cancers, including tumor growth.
- The specific role of miR-539 in pancreatic cancer (PC) pathogenesis remains unclear.
Purpose of the Study:
- To investigate the expression of miR-539 in pancreatic cancer specimens.
- To explore the functional role of miR-539 in PC cell growth and its relationship with TWIST1.
- To determine if TWIST1 is a direct target of miR-539.
Main Methods:
- Real-time quantitative polymerase chain reaction (qRT-PCR) for miRNA and gene expression analysis.
- In vitro experiments using PANC-1 cells with miR-539 mimics to assess tumor growth.
- Luciferase reporter assay to validate TWIST1 as a direct target of miR-539.
Main Results:
- miR-539 expression was significantly downregulated in PC tissues compared to controls.
- Upregulated TWIST1 expression was observed in PC tissues.
- Overexpression of miR-539 suppressed xenograft tumor growth in PANC-1 cells.
- TWIST1 was confirmed as a direct target gene of miR-539.
Conclusions:
- miR-539 plays a crucial role in the development and progression of pancreatic cancer.
- The interaction between miR-539 and TWIST1 is significant in PC.
- miR-539 represents a potential therapeutic target for pancreatic cancer treatment.
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