Relationship between MAP3K5 and Epstein-Barr virus-encoded miR-BART22 expression in nasopharyngeal carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To detect the expression of MAP3K5 and miR-BART22 encoded by Epstein-Barr virus and explore their relationship in nasopharyngeal carcinomas (NPCs).</p><p><b>METHODS</b>Fifty-three archived specimens of NPCs and 30 nasopharyngitis specimens were collected for detecting the expression of EBERs and miR-BART22 by in situ hybridization, and the expression of MAP3K5 was detected using immunohistochemistry. Ten fresh NPC and 10 fresh nasopharyngitis specimens were also obtained for determining the protein expression of MAP3K5 by Western blotting.</p><p><b>RESULTS</b>EBERs were positive in all the 53 NPC specimens, and miR-BART22 was positive in 49 specimens; all the 30 nasopharyngitis specimens were negative for EBER or miR-BART22. In the 53 NPC tissues, 50 were negative for MAP3K5 expression in the cancer areas but positive in the adjacent mucosal areas, with the other 3 specimens showing a weak positivity (+). In the 30 nasopharyngitis specimens, 25 showed strong MAP3K5 positivity, 3 showed weak positivity and 2 were negative for MAP3K5 (P<0.001). Western blotting showed that the expression of MAP3K5 protein was significantly higher in nasopharyngitis than in NPC tissues (P=0.029). The expression of MAP3K5 and miR-BART22 was inversely correlated (P<0.001).</p><p><b>CONCLUSION</b>Compared with the adjacent mucosal tissues, NPC tissues have a lower expression of MAP3K5 but a higher expression of miR-BART22. The expression of MAP3K5 and miR-BART22 is inversely correlated, suggesting the possibility of MAP3K5 to serve as target gene of EBV miR-BART22. miR-BART22 may inhibit the expression of MAP3K5, thus reducing the protein phosphorylation of MAPK pathway downstream genes, inhibiting NPC cell apoptosis, preventing their differentiation and promoting their escape from immune surveillance.</p>

Role of vascular endothelial growth factor receptor 1-positive hematopoietic progenitor cell clusters in human colorectal carcinoma metastasis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the relation of vascular endothelial growth factor receptor 1 (VEGFR1)-positive hematopoietic progenitor cell with the metastasis of human colorectal carcinoma.</p><p><b>METHODS</b>Human colorectal cancer cells SW480/M5 were implanted into BALB/c nude mice, and the tumor tissue blocks were re-implanted into the colon of nude mice. The quantity and percentage of VEGFR1-positive hematopoietic progenitor cells and human colorectal cancer cells in the pre-metastatic location were observed with flow cytometry, and the expression of metastasis-related factors was detected using Western blotting.</p><p><b>RESULTS</b>Bone marrow-derived hematopoietic progenitor cells expressing VEGFR1 were found in the common pre-metastatic sites and formed cell clusters before the arrival of the tumor cells, but these cells were not detected in nude mice without tumor implantation. In the course of tumor metastasis, the expression of the proteinases including matrix metalloproteinase 9 and stromal cell-derived factor 1 gradually intensified within the metastatic niche.</p><p><b>CONCLUSION</b>The formation of VEGFR1-positive hematopoietic progenitor cellular clusters is accompanied by the metastasis of human colorectal cancer, and may enhance the expression of metastasis-related factors, suggesting its important role in the invasion and metastasis of colorectal cancer.</p>