High Glucose Concentrations Negatively Regulate the IGF1R/Src/ERK Axis through the MicroRNA-9 in Colorectal Cancer

Abstract

Studies have revealed that people with hyperglycemia have a high risk of colorectal cancer (CRC). Hyperglycemia may be responsible for supplying energy to CRC cells. However, the potential molecular mechanism for this association remains unclear. Furthermore, microRNA-9 (miR-9) has a tumor-suppressive function in CRC. Aberrant reduced expression of miR-9 is involved in the development and progression of malignancy caused by a high glucose (HG) concentration. In this study, we used an HG concentration to activate miR-9 downregulation in CRC cells. Our results indicated that miR-9 decreased the insulin-like growth factor-1 receptor (IGF1R)/Src signaling pathway and downstream cyclin B1 and N-cadherin but upregulated E-cadherin. The HG concentration not only promoted cell proliferation, increased the G1 population, and modulated epithelial-to-mesenchymal transition (EMT) protein expression and morphology but also promoted the cell migration and invasion ability of SW480 (low metastatic potential) and SW620 (high metastatic potential) cells. In addition, low glucose concentrations could reverse the effect of the HG concentration in SW480 and SW620 cells. In conclusion, our results provide new evidence for multiple signaling pathways being regulated through hyperglycemia in CRC. We propose that blood sugar control may serve as a potential strategy for the clinical management of CRC.

Colorectal cancer-derived exosomal miR-106b-3p promotes metastasis by down-regulating DLC-1 expression

“…Matrigel invasion assays were performed to measure the invasive ability of different CRC cells ( Figure 3A). According to the results, SW480 cells had low invasive potential, and KM12SM cells had high invasive potential, which was consistent with previous results [21][22][23]. Intriguingly, Spearman's test analysis showed that the invasive potential of different CRC cell lines positively correlated with cellular miR-106b-3p expression (r = 0.79, P < 0.01).…”

IL‐10 induces MC3T3‐E1 cells differentiation towards osteoblastic fate in murine model

“…We also discovered that IGF1R expression decreased in the calluses of mouse fracture samples with injection of agomiR‐7025‐5p. Previous studies demonstrated that abnormal IGF1R expression plays an important role in the pathogenesis of acute lymphoblastic leukaemia, adrenocortical carcinoma, colorectal cancer and Ewing sarcoma . Thus, our findings indicate that the miR‐7025‐5p/IGF1R axis may play an important role in bone metabolism processes including osteoblast differentiation.…”

Systematic Elucidation of the Mechanism of Quercetin against Gastric Cancer via Network Pharmacology Approach

“…IGF1R is a transmembrane receptor tyrosine kinase that promotes the progression and metastatic ability of GC [ 67 ]. It can inhibit the apoptosis of cancer cells through the activation of SRC and PI3K/AKT [ 68 , 69 ]. As a cytoplasmic protein tyrosine kinase, PTK2 can enhance cell motility, survival, and proliferation through effects on cancer cells and stromal cells in the tumor microenvironment [ 70 ].…”