RESUMO
BACKGROUND/AIMS: Methylation status plays a causal role in carcinogenesis in targeted tissues. However, the relationship between the DNA methylation status of multiple genes in blood leukocytes and colorectal cancer (CRC) susceptibility as well as interactions between dietary factors and CRC risks are unclear. METHODS: We performed a case-control study with 466 CRC patients and 507 cancer-free controls to investigate the association among the methylation status of individual genes, multiple CpG site methylation (MCSM), multiple CpG site heterogeneous methylation and CRC susceptibility. Peripheral blood DNA methylation levels were detected by performing methylation-sensitive high-resolution melting. RESULTS: Total heterogeneous methylation of CA10 and WT1 conferred a significantly higher risk of CRC (adjusted odds ratio [ORadjusted], 5.445; 95% confidence interval [CI], 3.075 to 9.643; ORadjusted, 1.831; 95% CI, 1.100 to 3.047; respectively). Subjects with high-level MCSM (MCSM-H) status demonstrated a higher risk of CRC (ORadjusted, 4.318; 95% CI, 1.529 to 12.197). Additionally, interactions between the high-level intake of fruit and CRH, WT1, and MCSM on CRC were statistically significant. CONCLUSIONS: The gene methylation status of blood leukocytes may be associated with CRC risk. MCSM-H of blood leukocytes was associated with CRC, especially in younger people. Some dietary factors may affect hypermethylation status and influence susceptibility to CRC.
Assuntos
Neoplasias Colorretais , Metilação de DNA/genética , Leucócitos/metabolismo , Proteínas Mitocondriais/genética , Proteínas do Tecido Nervoso/genética , Proteínas WT1/genética , Idoso , Biomarcadores Tumorais/genética , Carcinogênese/genética , Carcinogênese/metabolismo , Estudos de Casos e Controles , China , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Ilhas de CpG/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica , Interação Gene-Ambiente , Humanos , Leucócitos/patologia , Masculino , Pessoa de Meia-Idade , Regiões Promotoras GenéticasRESUMO
The present study was designed to assess the expression of microRNA-542-3p (miR-542-3p) in human colon cancer and investigate the possible molecular mechanisms underlying the effect of miR-542-3p on the growth and invasion of colon cancer cells. We found that miR-542-3p expression was downregulated in colon cancer patient tissues, compared with that observed in the control group. Silencing of miR542-3p expression significantly promoted cell viability and inhibited apoptosis. In addition, overexpression of miR-542-3p significantly reduced cell viability and promoted apoptosis in colon cancer cells. Meanwhile, silencing of miR-542-3p expression significantly suppressed PI3K and p-AKT and survivin protein expression, while overexpression of miR-542-3p significantly induced PI3K and p-AKT and survivin protein expression in colon cancer cells. PI3K inhibitor (LY294002) or survivin inhibitor (YM155) suppressed PI3K/AKT/survivin signaling and increased the anticancer effects of miR-542-3p on the apoptosis in colon cancer. The present study demonstrated that upregulation of miR-542-3p inhibited the growth and invasion of colon cancer cells through PI3K/AKT/survivin signaling, highlighting a novel therapeutic approach for the treatment of colon cancer.