| Summary: | 碩士 === 國立成功大學 === 臨床醫學研究所 === 102 === Chronic inflammation is a crucial event in progression of gastric cancer. Particularly, tumor-associated macrophages (TAMs) are part of inflammatory circuits that promote tumorigenesis. MicroRNAs (miRNAs) are involved in multiple biological activities as well as disease progression including cancer. However, little is known about the association between tumor miRNAs and TAMs. Previously, we compared the expression profile of miRNAs between gastric cancer cells alone and gastric cancer cells co-cultured with U937, and found that miR-210 expression in gastric cancer cells significantly increased after co-cultured. In this study, we sought to determine whether TAMs regulate tumor miR-210, and thus promoting tumorigenesis of gastric cancer. We first verified the correlation between miR-210 and TAMs in gastric cancer and found that miR-210 was up-regulated by TAMs in co-culture experiments. Furthermore, we also observed a positive correlation between miR-210 expression and TAMs in gastric cancer specimens. Overall survival in gastric cancer patients with higher CD204 expression was significantly reduced than patients with lower CD204 expression. In addition, inactivation of miR-210 attenuated TAMs-mediated gastric cancer cell migration. Using MetaCore, we found that NTN4, a regulator for cytoskeleton, is a putative target gene of miR-210. Indeed, miR-210 can block the luciferase activity of NTN4–3’UTR in gastric cancer cell. Moreover, expression of NTN4 was decreased in clinical specimens and gastric cancer cells after TAMs stimulation. Combined high NTN4 expression and lower miR-210 expression is associated with better survival in gastric cancer patients. Collectively, these findings extend our understanding of the function of miR-210 in the inflammation system and this newly identified TAMs/miR-210/NTN4 pathway can be a prognostic factor for gastric cancer patient survival and a potential therapeutic target in gastric cancer treatment.
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