Positive association between IL-16 rs1131445 polymorphism and cancer risk: a meta-analysis.

INTRODUCTION: The association between IL-16 rs1131445 polymorphism and cancer risk is not consistent or even contradictory, this meta-analysis aims to investigate the role of IL-16 gene rs1131445 polymorphisms in the risk of cancer. EVIDENCE ACQUISITION: A comprehensive online search was conducted in PubMed, EMBASE and CNKI databases to identify eligible studies. The case-control studies related IL-16 rs1131445 C/T polymorphism with the cancer susceptibility were selected according to the inclusion and exclusion criteria. After extracting the basic data information and quality of literature evaluation, the meta-analysis was performed by using STATA 12.0 software, with calculating odds ratio and 95% confidence interval, and further subgroup analysis, literature publication bias test and sensitivity analysis. EVIDENCE SYNTHESIS: There are totally 1677 cases and 1989 non-tumor controls finally involved. Meta-analysis showed that there are statistical correlations between the IL-16 rs1131445 C/T polymorphism and the cancer risk in Asian populations (TS vs. C, OR=0.80, 95%CI: 0.73-0.88; TT vs. TC, OR=0.75, 95%CI: 0.65-0.87; TT vs. CC, OR=0.69, 95% CI: 0.56-0.84; CC+TC vs. TT, OR=1.36, 95%CI: 1.19-1.55; CC vs. TC+TT, OR=1.27, 95%CI: 1.05-1.53) (all P<0.05). CONCLUSIONS: IL-16 rs1131445 C/T polymorphism is related to the susceptibility to cancer in Asians, suggesting that the C allelic gene of rs1131445 is significantly associated with an increasing cancer risk.

MiR-21/RASA1 axis affects malignancy of colon cancer cells via RAS pathways.

AIM: To determine how the oncogene miR-21 regulates the RAS signaling pathways and affects colon cancer cell behaviors. METHODS: RAS p21 GTPase activating protein 1 (RASA1) protein expression in six colon cancer cell lines was assessed by Western blot. Colon cancer RKO cells were chosen for transfection because they are KRAS wild type colon cancer cells whose RASA1 expression is significantly decreased. RKO cells were transfected with vectors overexpressing or down-regulating either miR-21 or RASA1. Furthermore, a luciferase reporter assay was used to determine whether RASA1 is a gene target of miR-21. Then, changes in mRNA and protein levels of RASA1, RAS-GTP, and other components of the RAS signaling pathways were assessed in transfected RKO cells by real-time quantitative reverse transcription-polymerase chain reaction, Western blot and immunoprecipitation. Finally, cell proliferation, apoptosis, invasion, and tumor formation ability were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye assay, flow cytometry, transwell assay, and animal experiment, respectively. RESULTS: RASA1 protein levels were significantly decreased in RKO cells compared with the other 5 colon cancer cell lines, and RASA1 was confirmed as a target gene of miR-21. Interestingly, RASA1 mRNA and protein levels in pre-miR-21-LV (up-regulation of miR-21) cells were lower than those in anti-miR-21-LV (down-regulation of miR-21) cells (P < 0.05). In addition, pre-miR-21-LV or siRASA1 (down-regulation of RASA1) cells showed higher cell proliferation, reduced apoptosis, increased expression of RAS-GTP, p-AKT, Raf-1, KRAS, and p-ERK1/2, and higher invasion and tumor formation ability, compared with control, anti-miR-21-LV or pcDNA3.1-RASA1 (up-regulation of RASA1) cells (P < 0.05). CONCLUSION: RASA1 is a target gene of miR-21, which promotes malignant behaviors of RKO cells through regulation of RASA1 expression.