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.
Highlights
According to cancer-related microRNA expression microarray research available in public databases, miR-362 expression is elevated in gastric cancer
MiR-362 was upregulated in human gastric cancer cell lines and tissues To identify miRNAs that may be involved in gastric cancer progression, we analyzed a published microarray-based, high-throughput miRNA expression dataset (E-TABM341, ArrayExpress)
We found that miR-362 expression was significantly upregulated in human gastric cancer tissues (n = 184) than that in normal gastric tissues (n = 169) (P < 0.001, Figure 1A)
Summary
According to cancer-related microRNA (miRNA) expression microarray research available in public databases, miR-362 expression is elevated in gastric cancer. Surgery is the main treatment for operable gastric cancer; recurrence and metastasis are very common [2,3]. The combination of surgery and chemotherapy has recently emerged as an effective strategy for gastric cancer therapy, improving disease-free survival and reducing the risk of recurrence and metastasis as compared with. Many studies have shown that activated NF-κB signaling is highly associated with tumorigenesis, tumor progression, and therapy resistance. It plays an important role in oncogenesis due to its anti-apoptosis and pro-proliferation activities [12,13,14,15]. Multiple studies have demonstrated that CYLD is a tumor suppressor associated with the inhibition of cell proliferation and induction of apoptosis [24,25]. CYLD downregulation leads to apoptosis resistance [26]
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