Knock Down of HMGA2 Suppresses Colorectal Cancer Progression through Inhibiting Angiogenesis via Compromising VEGFR2 Signaling in HUVECs

Abstract

Colorectal cancer is one of the major public health issues worldwide due to its high mortality and morbidity. Angiogenesis is the fundamental step of tumors transition from dormant to malignant state and it is recognized as one of the hallmarks of cancer. High mobility group AT-hook 2 encodes a small non-histone chromatinassociated protein that can modulate transcription by altering the chromatin architecture. Currently the mechanism by which high mobility group AT-hook 2 involved in angiogenesis in colorectal cancer has not been clarified. The expression of High mobility group AT-hook 2 was analyzed by immunohistochemistry, Western blotting and bioinformatics methods. cBioPortal and mExpress online tools were applied to explore the copy-number variation and methylation of high mobility group AT-hook 2 in colorectal cancer patients. Single cell data from gene expression omnibus was used to examine the specific cell type that contributed to the high mobility group AT-hook 2 expression in colorectal cancer. Lentivirus was used to knock down high mobility group AT-hook 2 in colorectal cancer cells and human umbilical vein endothelial cells was used to study angiogenesis. In the current study, we first detected the expression pattern of high mobility group AT-hook 2 in colorectal cancer patients and evaluated its clinical values and for the first time showed that copy number amplification contributed to the up regulation of high mobility group AT-hook 2 in colorectal cancer patients. By analyzing colorectal cancer single cell data we found that high mobility group AT-hook 2 was specifically up regulated in the colorectal epithelial cells. Furthermore, knocking down of high mobility group AT-hook 2 in colorectal cancer epithelial cells suppresses angiogenesis via dual regulation of vascular endothelial growth factor-A and semaphorin 3A in colorectal cancer through inactivating vascular endothelial growth factor receptor 2 pathway in human umbilical vein endothelial cells. High mobility group AT-hook 2 might be a promising prognostic marker and target for treating advanced colorectal cancer patients.