High blood sugar levels significantly impact the prognosis of colorectal cancer patients through down-regulation of microRNA-16 by targeting Myb and VEGFR2

Abstract

The high prevalence of type 2 diabetes mellitus in colorectal cancer patients is a crucial public health issue worldwide. The deregulation of microRNAs has been shown to be associated with the progression of CRC; however, the effects of high blood sugar levels on miR deregulation and, in turn, CRC remain unexplored. In this study, 520 CRC patients were classified into two groups according to their blood sugar levels (≧110 or <110 mg/dL). Clinicopathologic features, clinical outcomes, and serum miR-16 levels of the two groups were then analyzed, while cell cycles, cell proliferation, migration, and cellular miR-16 expression were investigated via D-(+)-glucose administration. Additionally, the target genes of miR-16 were identified. Through multivariate analysis, both the disease-free survival and overall survival of the CRC patients were found to be associated with the UICC stage, perineural invasion, and blood glucose levels (P < 0.05). Serum miR-16 levels were significantly lower in the high blood glucose patients than in the normal blood glucose patients (P = 0.0329). With D-(+)-glucose administration, the proliferation and migration of CRC cells in vitro increased remarkably (P < 0.05), while their accumulation in the G1 phase decreased significantly. Cellular miR-16 expression was suppressed by D-(+)-glucose administration. The expression levels of two target genes, Myb and VEGFR2, were affected significantly by miR-16, while glucose administration inhibited miR-16 expression and enhanced tumor cell proliferation and migration. Hyperglycemia can impact the clinical outcomes of CRC patients, likely by inhibiting miR-16 expression and the expression of its downstream genes Myb and VEGFR2.

The relationship between diabetes and colorectal cancer prognosis: A meta-analysis based on the cohort studies

“…In our meta-analysis, year of publication ranged from 2003 to 2016, and the regions included 2 American countries[7, 13–15, 18, 19, 27, 30, 33, 37, 41, 42, 45, 46], 6 European countries[6, 11, 17, 28, 32, 39, 40, 44], 2 Asian countries[8, 9, 12, 16, 20, 29, 34–36, 38, 43, 47] and 1 Oceania country[31]; the included studies contained 15 retrospective[9, 10, 14, 16–20, 27, 33, 36, 37, 39, 41, 47] and 21 prospective[6–8, 11–13, 15, 28–32, 34, 35, 38, 40, 42–46] cohort studies; the sample size ranged from 391 to 1056243, and the mean age of study ranged from 46.4 to 72.07. In DM ascertainment, 25 studies[6, 8, 9, 11–15, 18, 19, …”

“…In DM ascertainment, 25 studies[6, 8, 9, 11–15, 18, 19, 28, 29, 31, 33–37, 39–42, 44–46] used the method of medical records, 5 studies[16, 20, 38, 43, 47] used the method of blood sugar test, and 6 studies[7, 10, 17, 27, 30, 32] used the method of self-reported. To avoid the effects of confounders, we preferred to extract the adjusted outcome effect estimates, but we still found that the outcome effect estimates of 4 studies were not adjusted.…”

TES inhibits colorectal cancer progression through activation of p38

“…For the wound-healing assay, as described in earlier studies [74–78], cells were plated and the monolayer of the cells was gently scratched with sterile micropipette tips, washed twice with PBS to remove cell debris, and incubated at 37°C with serum-free culture medium for serum starvation. The area of the gap at 0 h and the residual gap at 36 h after wounding of five random locations were acquired using a digital camera and microscope.…”

Energy sensing pathways: Bridging type 2 diabetes and colorectal cancer?

“…In a meta-analysis including 26 observational studies in patients with colorectal cancer [13] it is found that diabetic patients have a 17% increased risk of all-cause mortality and a 12% increased risk of cancer-specific mortality, compared to those without diabetes. The disease-free survival and overall survival of the CRC patients were also associated with blood glucose levels in a multivariate analysis [14]. Results from one pathologic analysis has found that patients with diabetes have deeper tumor invasion, greater lymphovascular invasion, and higher TNM staging compared to those without diabetes [15].…”