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Published on: January 7, 2019
Hsa-miR-202-3p, up-regulated in type 1 gastric neuroendocrine neoplasms, may target DUSP1
Dou Dou1, Yan-Fen Shi2, Qing Liu3
1Department of Integrative Oncology, China-Japan Friendship Hospital; Beijing University of Chinese Medicine, Beijing 100029, China.
Aim:
To detect abnormal microRNA (miRNA) expression in type 1 gastric neuroendocrine neoplasms (g-NENs) and find potential target genes.
Methods:
Tumour tissues from patients with type 1 g-NENs were used as experimental samples, and gastric mucosal tissues from the same patients obtained during gastroscopy review after several months were used as control samples. miRNA expression was examined with Agilent human miRNA chips and validated via RT-PCR. Three types of target gene prediction software (TargetScan, PITA, and microRNAorg) were used to predict potential target genes of the differentially expressed miRNAs, and a dual-luciferase reporter assay system was used for verification.
Results:
Six miRNAs were significantly upregulated or downregulated in the tumours compared to the control samples. Among them, miR-202-3p was extraordinarily upregulated. RT-PCR of seven sample sets confirmed that miR-202-3p was upregulated in tumour tissues. In total, 215 target genes were predicted to be associated with miR-202-3p. Among them, dual-specificity phosphatase 1 (DUSP1) was reported to be closely related to tumour occurrence and development. The dual-luciferase reporter assay showed that miR-202-3p directly regulated DUSP1 in 293T cells.
Conclusion:
miR-202-3p is upregulated in type 1 g-NEN lesions and might play important roles in the pathogenesis of type 1 g-NENs by targeting DUSP1.
Insights
MicroRNA (miRNA) miR-202-3p is upregulated in type 1 gastric neuroendocrine neoplasms (g-NENs). This dysregulation may contribute to g-NEN development by targeting dual-specificity phosphatase 1 (DUSP1).
Area of Science:
- Gastroenterology
- Oncology
- Molecular Biology
Background:
- Type 1 gastric neuroendocrine neoplasms (g-NENs) are rare tumors with incompletely understood pathogenesis.
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are implicated in various cancers.
Purpose of the Study:
- To identify differentially expressed miRNAs in type 1 g-NENs.
- To predict and validate target genes of these miRNAs, focusing on their role in tumorigenesis.
Main Methods:
- miRNA expression profiling using Agilent human miRNA chips on tumor and adjacent normal gastric tissues.
- Validation of differentially expressed miRNAs via RT-PCR.
- In silico prediction of miRNA targets using TargetScan, PITA, and microRNAorg.
- Experimental verification of miRNA-target interaction using a dual-luciferase reporter assay.
Main Results:
- Six miRNAs showed significant differential expression in type 1 g-NENs compared to controls.
- miR-202-3p was markedly upregulated in tumor tissues, confirmed by RT-PCR.
- Bioinformatic analysis predicted 215 target genes for miR-202-3p.
- Dual-luciferase reporter assay confirmed direct regulation of dual-specificity phosphatase 1 (DUSP1) by miR-202-3p.
Conclusions:
- miR-202-3p is significantly upregulated in type 1 g-NEN lesions.
- The miR-202-3p/DUSP1 axis is a potential key player in the pathogenesis of type 1 g-NENs.
- Targeting miR-202-3p or its downstream effectors like DUSP1 may offer therapeutic strategies for g-NENs.
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