Colorectal cancer (CRC) is one of the most common cancers worldwide, with a particularly high incidence in developed countries. Distant metastasis and recurrence are the main causes of CRC-related deaths. MicroRNAs (miRNAs) in the serum make them potential biomarkers for cancers, as reported in serum or tumor tissues from CRC patients. In this study, we found that miR-612 expression was significantly lower in CRC tissues or cells compared with peritumor tissues or normal cells, and lower in metastatic CRC specimens compared with non-metastatic specimens, whereas AKT2 exhibited opposite trend. Gain-of-function and loss-of-function assays showed that miR-612 inhibited CRC cell proliferation and migration in vitro by Cell Counting Kit-8 and transwell assays. Further analysis revealed that miR-612 directly suppressed AKT2, which in turn inhibited the downstream epithelial–mesenchymal transition-related signaling pathway. These results were additionally validated in vivo by tumorigenesis and liver metastasis experiments. The results of this study suggested a critical role of miR-612 in the development of CRC.

IL1 receptor antagonist (IL1RA) and IL1beta (IL1β), members of the pro-inflammatory cytokine interleukin-1 (IL1) family, play a potential role against infection and in the pathogenesis of cancers. The variable number of tandem repeats (VNTR) polymorphism in the second intron of the IL1 receptor antagonist gene (IL1-RN) and a polymorphism in exon 5 of IL1B (IL1B+3954C>T, rs1143634) have been suggested in predisposition to cancer risk. However, studies have shown inconsistent results. To validate any association, a meta-analysis was performed with 14,854 cases and 19,337 controls from 71 published case–control studies for IL1-RN VNTR and 33 eligible studies contained 7,847 cases and 8917 controls for IL1B +3954. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated from comparisons to assess the strength of the association. There was significant association between the IL1-RN VNTR polymorphism and the risk of cancer for any overall comparison. Furthermore, cancer type stratification analysis revealed that there were significantly increased risks of gastric cancer, bladder cancer and other cancer groups. Infection status analysis indicated that the H. pylori or HBV/HCV infection and IL1-RN VNTR genotypes were independent factors for developing gastric or hepatocellular cancers. In addition, a borderline significant association was observed between IL1B+3954 polymorphism and the increased cancer risk. Although some modest bias could not be eliminated, this meta-analysis suggested that the IL1-RN VNTR polymorphisms may contribute to genetic susceptibility to gastric cancer. More studies are needed to further evaluate the role of the IL1B+3954 polymorphism in the etiology of cancer.

Chemokine and the chemokine receptor have a key role in the tumor progress. Here, we supposed that CCR7 might induce the invasion, migration, and epithelial–mesenchymal transition (EMT) process of breast cancer. In this research, human breast cancer MCF‐7 and MDA‐MB‐231cells were treated with CCL19 and small‐interfering RNA (CCR7 siRNA) for activation and inhibition of CCR7, respectively. Cell invasion and transwell assays were used to detect the effect of CCR7 on invasion and migration. The results demonstrated that CCL19 mediated cell invasion and migration by inducing the EMT, with downregulation of E‐cadherin and up‐regulation of N‐cadherin and vimentin levels. On the other hand, knockdown of CCR7 revealed the changes compared with CCL19 group and the control group. Knockdown of CCR7 inhibits CCL19‐induced breast cancer cell proliferation, the cell cycle, migration, invasion and EMT. Moreover, we demonstrated that CCL19‐induced AKT phosphorylation; however, CCR7 siRNA suppressed CCL19‐induced AKT phosphorylation, a key regulator of tumor metastasis. In conclusion, all findings demonstrated that CCL19/CCR7 axis regulated EMT progress in breast cancer cells and mediated the tumor cell invasion and migration process via activation of AKT signal pathway. Our results suggested that CCR7 may regard as a therapeutic target for the breast cancer treatment.