Dysregulation of MiR-30a-3p/Gastrin Enhances Tumor Growth and Invasion throughSTAT3/MMP11 Pathway in Gastric Cancer
Received 17 October 2019
Accepted for publication 26 July 2020
Published 25 August 2020 Volume 2020:13 Pages 8475—8493
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Sanjay Singh
Yan Liu,1,2,* Meng Gao,3,* Juan An,2,* Xin Wang,4 Yan Jia,4 Junfeng Xu,4 Jihai Zhu,5 Jiantao Cui,1 Wenmei Li,1 Rui Xing,1 Li Song,6 Kejia Liu,6 Yuqi He,4 Jianqiu Sheng,4 Shengmei Qi,3 Yuanming Pan,1,4 Youyong Lu1
1Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Cancer Hospital/Institute, School of Oncology, Peking University, Beijing, Haidian District 100142, People’s Republic of China; 2Department of Basic Medical Sciences, Medical College of Qinghai University, Xining City, Qinghai 810001, People’s Republic of China; 3OnkoRx Ltd. Beijing, Beijing, Haidian District 100085, People’s Republic of China; 4Department of Gastroenterology, The 7th Medical Center of Chinese PLA General Hospital, Beijing, Dongcheng District 100700, People’s Republic of China; 5Department of Cardiothoracic Surgery, The Affiliated Hospital of Qinghai University, Xining City, Qinghai 810001, People’s Republic of China; 6Yidu Cloud (Beijing) Technology Co., Ltd. 8F, Health Work, Beijing, Haidian District 100083, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Youyong Lu, MD, Ph.D.
Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Cancer Hospital/Institute, School of Oncology, Peking University, Beijing 100142, People’s Republic of China
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: gastrin, proliferation, invasion, miR-30a-3p, STAT3/MMP11 pathway, gastric cancer
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