miRNA-320 inhibits colitis-associated colorectal cancer by regulating the IL-6R/STAT3 pathway in mice
Mengyao Wu, Yuxin Luo, Wen-Xiu Jia, Dandan Wang, Donglei Sun, Jia Song, Jing Wang, Weiwei Niu, Xiaolan Zhang
Abstract
Background: Colitis-associated colorectal cancer (CAC) is a serious complication of inflammatory bowel disease (IBD). microRNA-320 (miRNA-320) promotes intestinal mucosal barrier repair in IBD and inhibits tumor progression. However, the role of miRNA-320 in the progression of CAC remains to be defined. We studied the mechanisms of miRNA-320 in the progression of CAC in mice. Methods: CAC was induced in mice (C57BL/B6) by the administration of azoxymethane (AOM) and dextran sulfate sodium (DSS), and the mice were given a lentiviral vector (LV) overexpressing mmu-miRNA-320. The level of miRNA-320 was analyzed by quantitative real-time polymerase chain reaction (qPCR). Colonic inflammation, histological analysis, and tumorigenesis were evaluated. Ki-67 in colonic tissues was examined by immunohistochemistry. B-cell lymphoma-extra large (BCL-xl) and proliferating cell nuclear antigen (PCNA) expression was examined by Western blot. Furthermore, the proliferation, migration, and invasion of colorectal cancer (CRC) cells were evaluated. The levels of interleukin-6 receptor (IL-6R), signal transducer and activator of transcription 3 (STAT3), and phosphorylated-signal transducer and activator of transcription 3 (p-STAT3) were examined by Western blot and qPCR. Results: . Silencing IL-6R expression partially reversed the IL-6R/STAT3-suppressing and tumor-inhibiting effect of miRNA-320. Conclusions: miRNA-320 inhibits tumorigenesis in mice with CAC by suppressing IL-6R/STAT3 expression, and IL-6R is a target gene of miRNA-320.