MicroRNA-362 induces cell proliferation and apoptosis resistance in gastric cancer by activation of NF-κB signaling

Jin-tang Xia,Lian‐zhou Chen,Wei-hua Jian,Kebing Wang,Yong-zhen Yang,Wei-ling He,Yu-Long He,De Chen,Wen Li

Published 2014 in Journal of Translational Medicine

ABSTRACT

BackgroundAccording to cancer-related microRNA (miRNA) expression microarray research available in public databases, miR-362 expression is elevated in gastric cancer. However, the expression and biological role of miR-362 in gastric progression remain unclear.MethodsmiR-362 expression levels in gastric cancer tissues and cell lines were determined using real-time PCR. The roles of miR-362, in promoting gastric cancer cell proliferation and apoptosis resistance, were assessed by different biological assays, such as colony assay, flow cytometry and TUNEL assay. The effect of miR-362 on NF-κB activation was investigated using the luciferase reporter assay, fluorescent immunostaining.ResultsMiR-362 overexpression induced cell proliferation, colony formation, and resistance to cisplatin-induced apoptosis in BGC-823 and SGC-7901 gastric cancer cells. MiR-362 increased NF-κB activity and relative mRNA expression of NF-κB–regulated genes, and induced nuclear translocation of p65. Expression of the tumor suppressor CYLD was inhibited by miR-362 in gastric cancer cells; miR-362 levels were inversely correlated with CYLD expression in gastric cancer tissue. MiR-362 downregulated CYLD expression by binding its 3′ untranslated region. NF-κB activation was mechanistically associated with siRNA-mediated downregulation of CYLD. MiR-362 inhibitor reversed all the effects of miR-362.ConclusionThe results suggest that miR-362 plays an important role in repressing the tumor suppressor CYLD and present a novel mechanism of miRNA-mediated NF-κB activation in gastric cancer.

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