Downregulation of Manic fringe impedes angiogenesis and cell migration of renal carcinoma.

ABSTRACT

Clear cell renal cell carcinoma (ccRCC) is a highly angiogenic cancer. Manic fringe (MFng) is elevated in ccRCC compared to the normal kidney. However, its role in ccRCC tumour angiogenesis remains elusive. This study seeks to determine the expression pattern of MFng in ccRCC blood vessels and its role in angiogenesis. The association between MFng and the blood vessels was established through online compendia, immunohistochemistry and qPCR analyses. The anti-angiogenic potential of lentiviral-mediated MFng knockdown in endothelial cells (EC shMFng) was assessed for viability, proliferation, apoptosis, migration, adhesion, cell cycle, vessel sprouting, and molecular expression of adhesion and apoptosis markers. Finally, EC shMFng were co-cultured with 786-0 renal cancer cells to determine their impact on cancer cell migration. The online dataset analyses and immunostaining on ccRCC tissues revealed high expression of MFng in ECs. MFng and CD31/PECAM-1 genes were up-regulated in ccRCC tissue samples compared to normal kidney tissues. EC shMFng demonstrated decreased cell viability due to G1 cell cycle arrest and reduced Ki-67 protein expression. In addition, shMFng down-regulated endothelial adhesion molecules and hindered EC migration, network formation and sprouting, compared to their respective empty vector (EV) controls. Co-culture assay of EC shMFng with 786-0 renal cancer cells inhibited cancer cell migration. These findings underscore the potential role of MFng in ECs in influencing renal cancer cell migration, thus opening an avenue for anti-angiogenic strategy targeting MFng to treat ccRCC.