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Investigational New Drugs
Published in: Investigational New Drugs 4/2020

01-08-2020 | Gastric Cancer | PRECLINICAL STUDIES

Identification of HGF as a novel target of miR-15a/16/195 in gastric cancer

Authors: Dongying Liu, Haiyang Zhang, Shaohua Ge, Dan Lin, Jiayi Han, Guoguang Ying, Yi Ba

Published in: Investigational New Drugs | Issue 4/2020

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Summary

Background Gastric malignancy is the third most frequently encountered cancer globally and have been documented to confer extremely poor prognosis, given their limited treatment options. The up-regulation of hepatocyte growth factor (HGF) has been found in various tumor tissues, including GC tissue, and has been linked with tumor development. Nevertheless, the pathways leading to HGF upregulation have yet to be fully explored. Methods Immunohistochemistry (IHC) assay was used to detect HGF expression in human gastric tumor tissues, while western blotting allowed quantification of protein levels. Bioinformatics tools were used to predict potential miRNA that may target HGF mRNA. Relative levels of miR-15a/16/195 as well as the target mRNA levels were analyzed with qRT-PCR. Direct targeting between miRNA and mRNA was then validated by luciferase assay. Finally, a mouse xenograft tumor model was selected to demonstrate the in vivo effects of miR-15a/16/195. Results HGF protein expressions were markedly raised, while miR-15a/16/195 levels were dramatically down-regulated in tumor tissues of GC. miR-15a/16/195 were shown to directly bind with the 3′-UTR of HGF mRNA. This study demonstrated that HGF can be repressed by overexpressed miR-15a/16/195, which resulted in the suppression of GC cell proliferation and migration. Furthermore, in the xenograft mouse model, miR-15a/16/195 were also found to have a tumor growth suppression effect. Conclusions miR-15a/16/195 suppresses tumorigenesis by targeting HGF and may have a potential therapeutic application in the clinical treatment of GC.
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Metadata
Title
Identification of HGF as a novel target of miR-15a/16/195 in gastric cancer
Authors
Dongying Liu
Haiyang Zhang
Shaohua Ge
Dan Lin
Jiayi Han
Guoguang Ying
Yi Ba
Publication date
01-08-2020
Publisher
Springer US
Published in
Investigational New Drugs / Issue 4/2020
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-019-00834-z

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