SEMA3B-AS1通过抑制Semaphorin 3B依赖的VEGF信号通路激活来抑制结肠癌的进展。
SEMA3B-AS1 suppresses colorectal carcinoma progression by inhibiting Semaphorin 3B-dependent VEGF signaling pathway activation.
发表日期:2023 Oct
作者:
Yi-Qing Wang, Hui Chen, Shuang Xu, Cong-Rui Liao, Anran Xu, Yue Han, Min-Hui Yang, Li Zhao, Sha-Sha Hu, Lan Wang, Qing-Yuan Li, Ling-Ying Zhan, Yan-Qing Ding, Shuang Wang
来源:
Epigenetics & Chromatin
摘要:
越来越多的证据表明,长链非编码RNA(lncRNA)在多种癌症的肿瘤发生和进展中具有显著的调控作用。最近发现,长链非编码RNA Semaphorin 3B(SEMA3B)反义RNA 1(SEMA3B-AS1)在一些癌症中表达异常。然而,其在结直肠癌(CRC)中的潜在功能和机制尚未被研究。在这里,我们展示了SEMA3B-AS1是CRC进展的关键调节因子。我们发现SEMA3B-AS1在CRC细胞系和组织中表达下调。SEMA3B-AS1的下调与CRC患者的生存率显著相关。SEMA3B-AS1的过表达在体内和体外明显减少了CRC的细胞生长和转移。此外,SEMA3B-AS1通过招募EP300促进SEMA3B启动子处的H3K9乙酰化,促进了其同义基因SEMA3B的表达。此外,我们证实SEMA3B-AS1通过影响SEMA3B-NRP1轴调控的血管内皮生长因子信号通路激活来抑制CRC的血管生成。我们的研究揭示了SEMA3B-AS1在抑制CRC恶性进展中的新机制,并强调其作为CRC干预的新潜在诊断标记和治疗靶点的概率。© 2023年作者。MedComm由四川国际医学交流与促进协会(SCIMEA)和约翰·威利·澳大利亚有限公司出版。
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.© 2023 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.