Hsa-miR-202-3p, up-regulated in type 1 gastric neuroendocrine neoplasms, may target DUSP1

doi:10.3748/wjg.v24.i5.573

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World Journal of Gastroenterology

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World J Gastroenterol. Feb 7, 2018; 24(5): 573-582
Published online Feb 7, 2018. doi: 10.3748/wjg.v24.i5.573

Hsa-miR-202-3p, up-regulated in type 1 gastric neuroendocrine neoplasms, may target DUSP1

Dou Dou, Yan-Fen Shi, Qing Liu, Jie Luo, Ji-Xi Liu, Meng Liu, Ying-Ying Liu, Yuan-Liang Li, Xu-Dong Qiu, Huang-Ying Tan

Dou Dou, Yuan-Liang Li, Xu-Dong Qiu, Department of Integrative Oncology, China-Japan Friendship Hospital; Beijing University of Chinese Medicine, Beijing 100029, China

Yan-Fen Shi, Jie Luo, Department of Pathology, China-Japan Friendship Hospital, Beijing 100029, China

Qing Liu, Meng Liu, Huang-Ying Tan, Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China

Ji-Xi Liu, Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China

Ying-Ying Liu, Department of Integrative Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471009, Henan Province, China

Author contributions: Dou D and Shi YF contributed equally to this work and should be considered co-first authors; Tan HY, Dou D and Shi YF designed the research; Dou D, Liu Q, Liu JX, and Li YL performed the research; Shi YF, Luo J and Qiu XD analyzed the data; Dou D, Liu M and Liu YY wrote the paper; Shi YF and Tan HY revised the paper.

Supported by the National Natural Science Foundation of China, No. 81673763.

Institutional review board statement: The study was reviewed and approved by the China-Japan Friendship Hospital Institutional Review Board.

Conflict-of-interest statement: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the reported research.

Data sharing statement: No additional data are available.

Correspondence to: Huang-Ying Tan, MD, PhD, Professor, Department of Integrative Oncology, China-Japan Friendship Hospital, No. 2, Yinghuadong Street, Beijing 100029, China. tanhuangying@263.net

Telephone: +86-10-53236555 Fax: +86-10-53236555

Received: November 5, 2017
Peer-review started: November 6, 2017
First decision: November 22, 2017
Revised: December 3, 2017
Accepted: December 12, 2017
Article in press: December 12, 2017
Published online: February 7, 2018
Processing time: 86 Days and 10.4 Hours

Abstract

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.

Keywords: MicroRNA; Type 1 g-NEN; Neuroendocrine neoplasm; Recurrence

Core tip: In this study, we have innovatively used chip technology to study microRNAs in type 1 gastric neuroendocrine neoplasms. We found miR-202-3p was extraordinarily upregulated in the tumours compared to the control samples. Interestingly, although miR-202 belongs to let-7, a famous cancer-suppressing family, some studies have reported its oncogenic potential in some tumours. Then, we found that DUSP1 could be a target gene of miR-202-3p and was closely related to tumour occurrence and development. Finally, we successfully showed that the miR-202-3p directly regulated DUSP1 in tool cells.