SCARA5 in bone marrow stromal cell-derived exosomes inhibits colorectal cancer progression by inactivating the PI3K/Akt pathway.

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer worldwide. Bone marrow stromal cells (BMSCs) play an essential role in tumor development by secreting exosomes. Scavenger receptor class A member 5 (SCARA5) is a newly identified tumor suppressor. This study aimed to investigate the effects of BMSCs-derived exosomes (BMSCs-Exos) on CRC development and to explore their regulatory mechanisms. BMSCs-Exos showed an oval-shaped, bilayer membrane structure. BMSCs-Exos inhibited growth and motility of CRC cells, while BMSCs-Exos with SCARA5 knockdown significantly promoted cell proliferation and movement. Exosomal SCARA5 also effectively suppressed colorectal tumor growth in mouse xenografts. Further analysis revealed that exosomal SCARA5 inhibited the phosphorylation of protein kinase B and phosphoinositide 3-kinase in both CRC cells and tumors. In conclusion, SCARA5 in BMSCs-Exos inhibited CRC progression by inactivating PI3K/Akt, thus suggesting the potential clinical application of SCARA5-containing BMSCs-Exos for CRC treatment.

Aspirin Inhibits Carcinogenesis of Intestinal Mucosal Cells in UC Mice Through Inhibiting IL-6/JAK/STAT3 Signaling Pathway and Modulating Apoptosis and Proliferation.

BACKGROUND: Colorectal cancer is related to ulcerative colitis. This study aimed to investigate the effects of aspirin on non-specific inflammation developing into cancer. METHODS: Ulcerative colitis model was generated by administrating azoxymethane/dextran sulfate sodium to mice. Weight, tumor size/ amount, and intestinal mucositis scores were analyzed. Inflammatory cell infiltration and atypical hyperplasia were determined with hematoxylin-eosin staining. Immunohistochemical assay was used to detect the proliferating cell nuclear antigen. Interleukin-6 and interleukin-10 were detected using enzyme-linked immunosorbent assay. Signal transducer and activator of transcription 3, phosphorylated-STAT3, cyclin D1, and suppressor of cytokine signaling 3 were examined with western blotting. RESULTS: Aspirin remarkably decreased tumor size/amount compared to those of the ulcerative colitis model group (P < .05). Interleukin-6 was increased and interleukin-10 was decreased in mice of ulcerative colitis model group compared with the control group (P < .05). Aspirin markedly reduced interleukin-6 and enhanced interleukin-10 compared to the ulcerative colitis model group (P < .05) induced Azoxymethane/dextran sulfate sodium inflammation (3 weeks) and atypical hyperplasia (8 weeks). Aspirin predominantly inhibited the "inflammation-atypical hyperplasia-cancer" process and alleviated inflammatory cell infiltration of mice in the ulcerative colitis model group. Aspirin promoted apoptosis and alleviated proliferating cell nuclear antigen of atypical hyperplastic intestinal mucosal cells at 8 weeks post-modeling. The expression of phosphorylated-STAT3, signal transducer and activator of transcription 3, cyclin D1, and suppressor of cytokine signaling 3 was significantly increased in mice of ulcerative colitis model group compared to the control group (P < .05). Aspirin remarkably decreased phosphorylated-STAT3, signal transducer and activator of transcription, and cyclin D1 expression compared with ulcerative colitis model group (P < .05). CONCLUSION: Aspirin inhibited carcinogenesis of intestinal mucosal cells in the ulcerative colitis model by inhibiting the interleukin-6/ Janus kinase/signal transducer and activator of transcription 3 signaling pathway and promoted apoptosis, thereby suppressing proliferation.

Exosomal miR-224-5p from Colorectal Cancer Cells Promotes Malignant Transformation of Human Normal Colon Epithelial Cells by Promoting Cell Proliferation through Downregulation of CMTM4.

Background: Interactions between malignant cells and neighboring normal cells are important for carcinogenesis. In addition, cancer cell-derived exosomes have been shown to promote the malignant transformation of recipient cells, but the mechanisms remain unclear. Methods: The level of miR-224-5p in CRC cell-derived exosomes was determined by RT-qPCR assay. In addition, PKH26 dye-labeled exosomes were used to assess the efficacy of the transfer of exosomes between SW620 and normal colon epithelial cell line CCD 841 CoN. Results: In this study, we found that overexpression of miR-224-5p significantly promoted the proliferation, migration, and invasion and inhibited the oxidative stress of SW620 cells. In addition, miR-224-5p can be transferred from SW620 cells to CCD 841 CoN cells via exosomes. SW620 cell-derived exosomal miR-224-5p markedly promoted proliferation, migration, and invasion of CCD 841 CoN cells. Meanwhile, SW620 cell-derived exosomal miR-224-5p notably decreased the expression of CMTM4 in CCD 841 CoN cells. Furthermore, SW620 cell-derived exosomal miR-224-5p significantly promoted tumor growth in a xenograft model in vivo. Conclusion: These findings suggested that SW620 cell-derived exosomal miR-224-5p could promote malignant transformation and tumorigenesis in vitro and in vivo via downregulation of CMTM4, suggesting that miR-224-5p might be a potential target for therapies in CRC.

Comparison of Water Immersion Versus Air Insufflation Colonoscopy Under Various Bowel Preparation Conditions.

BACKGROUND: To investigate the differences between water immersion (WI) and air insufflation (AI) for colonoscopy under various bowel preparation conditions. METHODS: In this study, 526 outpatients were randomly assigned to two groups, namely a WI group (n = 263) and an AI group (n = 263). During the procedure, the quality of bowel preparation, abdominal pain score, cecal intubation rate (CIR), adenoma detection rate (ADR), the intubation times, and other indicators were recorded. After reaching the cecum, each group of patients was subdivided into one of four grades (excellent, good, fair, and poor) according to the quality of bowel preparation. RESULTS: Under various bowel preparation conditions, the pain scores of the AI group were higher than those of the WI group (P < .05), but there was no significant difference between the two groups in CIR (P > .05). For the WI group compared with the AI group, the cecal intubation time (CIT) was prolonged under good bowel preparation (P = .045) and fair bowel preparation (P < .001). No significant differences were observed between the two groups on ADR in all patients (P = .476). CONCLUSION: Compared with AI colonoscopy, WI colonoscopy can decrease colonoscopy-related pain in patients for unsedated colonoscopy under various bowel preparation conditions, but there is no significant difference in CIR. WI colonoscopy requires longer CIT in patients with good and fair bowel preparation conditions. WI colonoscopy does not significantly increase ADR.

Effects of MDM4 Gene Regulation by miR-34a on LOVO Cell Proliferation.

This study aims to investigate the effects of regulation of murine double minute protein4 (MDM4) expression by microRNA (miR)-34a on the proliferation of colorectal cancer LOVO cells. Prediction results obtained using a gene microarray showed that MDM4 is a specific miR-34a target gene. The interaction between miR-34a and the 3'-untranslated region (UTR) of MDM4 was detected using a luciferase reporter system. The effect of miR-34a on MDM4 protein expression was detected by Western blotting, and the effect of miR-34a transfection on LOVO cell proliferation was detected using an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay and flow cytometry. The luciferase activity in LOVO cells after addition of pmirGLO-UTR+miR-34a mimic was only 44% of that obtained with pmirGLO-UTR+miR-34a (p<0.01), and the luciferase activity in LOVO cells after addition of pmir-GLO-mutUTR+miR-34a was 94% of that observed after pmirGLO-UTR+miR-34a addition (p=0.57). These results indicated that miR-34a interacted with the 3'-UTR of MDM4. Results of Western blotting revealed that MDM4 protein expression level in LOVO cells after addition of miR-34a mimic was 29% that of non-treated LOVO cells (p<0.05), indicating that miR-34a negatively regulates MDM4 protein expression. The growth rate of LOVO cells with miR-34a overexpression was significantly reduced compared with that of non-treated LOVO cells (p<0.05), indicating that miR-34a overexpression inhibits LOVO cell proliferation. miR-34a negatively regulates MDM4 gene expression to inhibit LOVO cell proliferation.