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Regulator of G-protein signaling 3 targeted by miR-126 correlates with poor prognosis in gastric cancer patients

Wang, Junqing; Zhou, Yunyun; Fei, Xiaochun; Chen, Xunhua; Zhu, Zhenggang

doi: 10.1097/CAD.0000000000000446
PRECLINICAL REPORTS
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The Wnt/β-catenin signaling pathway dominates numerous cellular processes including cell proliferation, differentiation, and epithelial–mesenchymal transition, which play a crucial role in human cancer malignancies. Regulator of G-protein signaling 3 (RGS3) is a pivotal molecule involved in the Wnt/β-catenin signaling pathway, which is worthy of intensive research as a potential target in cancer treatment. In this study, we found that RGS3 is significantly upregulated in gastric cancer (GC) tumor samples compared with normal samples from the analysis of two independent GC mRNA microarray datasets in the NCBI public database. Further immunohistochemistry assay and western-blot experiments confirmed this finding on the basis of the results of our own 102 paired GC specimens and three GC cell lines. We found that a high expression of RGS3 is associated with advanced TNM stages and more aggressive malignant behaviors. In addition, the association of overexpression of RGS3 and poor overall survival and progression-free survival outcomes suggests that RGS3 has the potential to serve as a molecular therapy target for GC. Interestingly, our pathways analysis and the follow-up dual-luciferase reporter assay showed that there is a direct 3′-untranslated region binding site between RGS3 mRNA and microRNA-126, a GC inhibitor. On the basis of all the above evidences, our findings suggest that overexpressed RGS3 regulated by microRNA-126 through the post-transcriptional modulation is associated significantly with a poor prognosis of GC patients.

Departments of aSurgery

bPathology

cShanghai Key Laboratory of Gastric Neoplasms

dShanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

eDepartment of Data Science, University of Mississippi Medical Center, Jackson, Mississippi, USA

* Junqing Wang and Yunyun Zhou contributed equally to the writing of this article.

Correspondence to Junqing Wang, MD, PhD, and Zhenggang Zhu, MD, PhD, Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197, Ruijin Er Road, Shanghai 20025, People’s Republic of China Tel: +1 4699517415; e-mails: wangjunqingmd@hotmail.com,scienceuse_labrjh@yeah.net

Received June 20, 2016

Accepted September 18, 2016

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