LncRNA LINC01503 promotes angiogenesis in colorectal cancer by regulating VEGFA expression via miR-342-3p and HSP60 binding
Dandan Zheng1
Xiya Zhang2
Jia Xu1
Shuwen Chen3
Bin Wang4
Xiaoqin Yuan1
1.Department of Anatomy,Histology and Embryology,Nanjing Medical University,Nanjing,Jiangsu 211166,China2.Jiangsu Key Laboratory of Oral Diseases,Nanjing Medical University,Nanjing,Jiangsu 210029,China3.Department of Clinical Medicine,First Clinical Medicine College,Nanjing Medical University,Nanjing,Jiangsu 210029,China4.Department of Gastroenterology,the Affiliated Changshu Hospital of Nantong University,Changshu No.2 People's Hospital,Suzhou,Jiangsu 215500,China
摘要：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.
机标关键词：linc01503expressionlncrnavegfacancerangiogenesisbindingcolorectal
分类号：R735.3(消化系肿瘤)
论文发表日期：2025-05-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：19( 286-304 )
英文信息