SEMA3B‐AS1 suppresses colorectal carcinoma progression by inhibiting Semaphorin 3B‐dependent VEGF signaling pathway activation

Abstract

Mounting evidence has demonstrated the considerable regulatory effects of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of various carcinomas. LncRNA Semaphorin 3B (SEMA3B) antisense RNA 1 (SEMA3B‐AS1) has been found to be dysregulated in a few carcinomas recently. However, its potential function and mechanism in colorectal carcinoma (CRC) have not yet been examined. Here we show that SEMA3B‐AS1 acts as a crucial regulator of CRC progression. We found that SEMA3B‐AS1 expression was downregulated in CRC cell lines and tissues. Downregulation of SEMA3B‐AS1 was significantly associated with poor survival in CRC patients. Overexpression of SEMA3B‐AS1 reduced the cell growth and metastasis of CRC in vivo and in vitro. In addition, SEMA3B‐AS1 promoted the expression of its sense‐cognate gene SEMA3B, a member of the Semaphorin family (SEMAs), by recruiting EP300 to induce H3K9 acetylation at the SEMA3B promoter. Furthermore, we proved that SEMA3B‐AS1 suppressed CRC angiogenesis by affecting the vascular endothelial growth factor signaling pathway activation which was regulated by the SEMA3B‐NRP1 axis. Our work unravels a novel mechanism of SEMA3B‐AS1 in the inhibition of CRC malignant progression and highlights its probability as a new promising diagnostic marker and therapeutic target for CRC interventions.

Effect of cellular senescence on the response of human peritoneal mesothelial cells to TGF-β

“…TGFBI protein is secreted and deposited in extracellular matrix 55 , 56 By interacting with integrins, it mediates cell adhesion and migration 57 – 59 and thus may regulate tumour growth and angiogenesis 60 . SEMA3B is also a known regulator of angiogenesis acting to inhibit competitively VEGF signalling pathway 61 . Since the peritoneal mesothelium is a well-established source of angiogenic activity in the peritoneum 62 and TGF-β is a potent inducer of VEGF in HPMCs 48 , it remains to be determined how the alterations in TGFBI and SEMA3B expression contribute to changes in the angiogenic potential in the aging mesothelium.…”

Elucidating the role of angiogenesis-related genes in colorectal cancer: a multi-omics analysis

“…Numerous genes and signaling pathways have been identified as critical regulators of angiogenesis, many of which are frequently overexpressed within tumors, thereby amplifying angiogenic signaling ( 6 ). In the context of CRC, several genes and molecular pathways such as vascular endothelial growth factor (VEGF) ( 7 ), platelet-derived growth factor (PDGF) ( 8 ), and fibroblast growth factor (FGF) ( 9 ), have been reported as associated with angiogenesis. As a result, targeting angiogenesis has emerged as a promising therapeutic strategy in CRC treatment.…”