MiR-92 suppresses proliferation and induces apoptosis by targeting EP4/Notch1 axis in gastric cancer
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Vivian Yvonne Shin1,*, Man-Ting Siu1,*, Xin Liu1, Enders K.O. Ng1, Ava Kwong1,2,3 and Kent-Man Chu1
1Department of Surgery, The University of Hong Kong, Hong Kong SAR
2Department of Surgery, Hong Kong Sanatorium and Hospital, Hong Kong SAR
3Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong SAR
*These authors contributed equally to this work
Kent-Man Chu, email: [email protected]
Vivian Yvonne Shin, email: [email protected]
Keywords: miR-92; NF-κB; EP4; Notch1; gastric cancer
Received: August 03, 2017 Accepted: February 27, 2018 Published: May 11, 2018
MiR-92a has been shown to be dysregulated in various cancers and exhibited differential role in carcinogenesis. In this study, we sought to delineate the functional role of miR-92a and its regulatory pathway in gastric cancer. MiR-92a expression were underexpressed in tissues of gastric cancer patients with the area under curve (AUC) of 0.78. Low expression in plasma was due to the increased promoter DNA methylation of miR-92a. Overexpression of miR-92a inhibited cell proliferation and invasion, and induced apoptosis. Furthermore, miR-92a reduced tumor growth in xenograft model. EP4 and Notch 1 were identified to be negatively regulated by miR-92a, and involved in cell growth. Moreover, NF-κB expression was inversely correlated with miR-92a in gastric cancer tissues and suppressed the expression of miR-92. This study unravels the tumor suppressive role of miR-92a involving EP4/Notch 1 signaling regulated by NF-κB in gastric cancer. Further studies on miR-92a and EP4/Notch1 may provide a new treatment strategy for gastric cancer.
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