RESUMEN
BACKGROUND: Despite a growing body of observational studies indicating a potential link between metabolic syndrome and colorectal cancer, a definitive causal relationship has yet to be established. This study aimed to elucidate the causal relationship between metabolic syndrome and colorectal cancer through Mendelian randomization. METHODS: We screened for instrumental variables associated with metabolic syndrome and its diagnostic components and with colorectal cancer through the use of a genome-wide association study database, and conducted a preliminary Mendelian randomization analysis. To corroborate the dependability of our conclusions, an additional dataset was used for replication analysis in a Mendelian randomization method, which was further integrated with a meta-analysis. RESULTS: Preliminary analysis using the inverse variance weighted method revealed positive correlations between metabolic syndrome (OR [95% CI] = 1.37[1.15-1.63], P = 5.02 × 10-4) and waist circumference (OR [95% CI] = 1.39[1.21-1.61], P = 7.38 × 10-6) and the risk of colorectal cancer. Replication analysis also revealed the same results: metabolic syndrome (OR [95% CI] = 1.24[1.02-1.51], P = 0.030) and waist circumference (OR [95% CI] = 1.23[1.05-1.45], P = 0.013). The meta-analysis results further confirmed the associations between metabolic syndrome (OR [95% CI] = 1.31[1.15-1.49], P < 0.001) and waist circumference (OR [95% CI] = 1.32[1.18-1.47], P < 0.001) and colorectal cancer. CONCLUSION: Our study indicated that metabolic syndrome increases the risk of CRC, particularly in patients with abdominal obesity.
RESUMEN
Recently, an increasing number of studies have reported that dysregulation of circular RNA (circRNA) expression plays critical roles in the progression of several cancers, including colorectal cancer (CRC). However, the detailed molecular mechanisms of circRNAs involvement in CRC remain largely unknown. Here, we confirmed that the level of circEGFR was significantly increased in CRC tissues compared to matched adjacent non-tumor tissues, and a high level of circEGFR was correlated with poor clinicopathological characteristics and poor prognosis in patients with CRC. Moreover, increased circEGFR expression promoted CRC cell proliferation, migration, and invasion in vitro. Mechanistically, circEGFR acted as a ceRNA for miR-106a-5p to relieve the repressive effect of miR-106a-5p on DDX5 mRNA. Moreover, circEGFR enhanced DDX5 expression, thereby upregulating p-AKT levels. Together, these findings showed that circEGFR promoted CRC cell proliferation, migration, and invasion through the miR-106a-5p/DDX5/AKT axis, and may serve as a promising diagnostic marker and therapeutic target for CRC patients.