Dysregulation of MiR-30a-3p/Gastrin Enhances Tumor Growth and Invasion throughSTAT3/MMP11 Pathway in Gastric Cancer

Onco Targets Ther. 2020 Aug 25:13:8475-8493. doi: 10.2147/OTT.S235022. eCollection 2020.

Abstract

Background: Gastrin (GAST) is a well-known hormone regulating gastric biofunctions in the secretion of acid and maintaining its structural integrity. Furthermore, the dysregulation of GAST is also involved in the development of various forms of cancer. However, there are some limitations for illustrating the cellular regulation of GAST and its regulatory mechanisms in gastric malignant transformation and the potential epigenetic regulators systematically.

Methods: We explored the role of GAST expression in gastric cancer (GC) and normal tissues with the clinical features and investigated the potential relationship between GAST and STAT3/MMP11 pathway by gain or loss of function analyses. Besides, based on our microRNA/mRNA expression profiles, miR-30a-3p was the potential epigenetic regulator and additional experiments were performed to identify the hypothesis.

Results: Elevated GAST expression was frequently detected in GC and was associated with worse outcomes (p<0.001). And we firstly demonstrated that GAST was negatively regulated by miR-30a-3p. Moreover, GAST induced GC cell proliferation, migration and invasion mediating STAT3/MMP11 pathway in this study.

Conclusion: MiR-30a-3p was the promising suppressor gene through negatively regulating the expression of GAST, and dysregulation of GAST was a prognostic signature associated cell proliferation and metastasis through STAT3/MMP11 pathway in GC.

Keywords: STAT3/MMP11 pathway; gastric cancer; gastrin; invasion; miR-30a-3p; proliferation.

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (No.81960451), Natural Science Foundation of Qinghai Province (No.2019-ZJ-7055), Chinese Postdoctoral Science Foundation (No.2017M613421), the CAS (Light of the West China) Program (No.2019-33), the Chunhui Plan of Ministry of Education of China (No.Z2017037), Beijing Municipal Science & Technology Commission (No.Z171100001017145) and Beijing Natural Science Foundation (No.7172213).