Colorectal cancer(CRC)ranks among the top five most common malignant tumors worldwide and has a high mortality rate.Angiogenesis plays an important role in CRC progression;however,anti-angiogenesis therapy still has m...Colorectal cancer(CRC)ranks among the top five most common malignant tumors worldwide and has a high mortality rate.Angiogenesis plays an important role in CRC progression;however,anti-angiogenesis therapy still has many limitations.Long non-coding RNAs(lncRNAs)participate in tumor progression by regulating the expression of vascular endothelial growth factor in metastatic CRC.Thus,targeting specific lncRNAs may provide some new hope for anti-angiogenic strategies.Through analyzing data from both clinical samples and The Cancer Genome Atlas database,we found that the lncRNA LINC01503 was specifically upregulated in CRC tissues and was associated with tumor progression and poor overall survival.We also demonstrated that LINC01503 enhanced the capacity for tube formation and migration of vascular endothelial cells,thus promoting CRC tumorigenesis by upregulating vascular endothelial growth factor A(VEGFA)expression in CRC cells.Mechanistically,LINC01503 promoted the expression of VEGFA by simultaneously regulating both mRNA and protein stability of VEGFA by binding to miR-342-3p and the chaperone HSP60,respectively.The upregulation of LINC01503 in CRC cells was attributed to the CREB-binding protein CBP/p300-mediated H3K27 acetylation of the LINC01503 promoter region.Taken together,our findings clarify the mechanism by which LINC01503 may promote CRC angiogenesis,implying that LINC01503 may serve as a potential prognostic biomarker and therapeutic target for CRC.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.81972288)the Scientific and Technologic Development Programme of Suzhou(Livelihood Science and Technology-Applied Basic Research in Healthcare,SYS2020057).
文摘Colorectal cancer(CRC)ranks among the top five most common malignant tumors worldwide and has a high mortality rate.Angiogenesis plays an important role in CRC progression;however,anti-angiogenesis therapy still has many limitations.Long non-coding RNAs(lncRNAs)participate in tumor progression by regulating the expression of vascular endothelial growth factor in metastatic CRC.Thus,targeting specific lncRNAs may provide some new hope for anti-angiogenic strategies.Through analyzing data from both clinical samples and The Cancer Genome Atlas database,we found that the lncRNA LINC01503 was specifically upregulated in CRC tissues and was associated with tumor progression and poor overall survival.We also demonstrated that LINC01503 enhanced the capacity for tube formation and migration of vascular endothelial cells,thus promoting CRC tumorigenesis by upregulating vascular endothelial growth factor A(VEGFA)expression in CRC cells.Mechanistically,LINC01503 promoted the expression of VEGFA by simultaneously regulating both mRNA and protein stability of VEGFA by binding to miR-342-3p and the chaperone HSP60,respectively.The upregulation of LINC01503 in CRC cells was attributed to the CREB-binding protein CBP/p300-mediated H3K27 acetylation of the LINC01503 promoter region.Taken together,our findings clarify the mechanism by which LINC01503 may promote CRC angiogenesis,implying that LINC01503 may serve as a potential prognostic biomarker and therapeutic target for CRC.
