Yang Jianguo, Deng Qican, Chen Zhenzhou, Chen Yajun, Fu Zhongxue
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, China.
Adv Clin Exp Med. 2024 Nov;33(11):1217-1236. doi: 10.17219/acem/175050.
Numerous studies have indicated the engagement of long non-coding RNA (lncRNA) in various cancer types, including colorectal cancer (CRC). However, the functional and mechanistic roles of lncRNAs in CRC remain largely elusive.
The aim of this study was to explore the function and mechanism of lncRNA BVES-AS1 in CRC.
The expression levels of BVES-AS1 were validated in CRC tissues and paired normal samples using quantitative real-time polymerase chain reaction (qPCR) Subsequently, the biological functions of BVES-AS1 in CRC cells were investigated both in vitro and in vivo. Various experimental techniques such as western blot, fluorescence in situ hybridization, RNA-sequencing (RNA-seq), biotin-labeled miRNA pulldown assay, dual-luciferase reporter gene assay, and RNA-protein immunoprecipitation (RIP) assay were employed to elucidate the potential mechanism of BVES-AS1.
The findings of this study demonstrated that BVES-AS1 expression was downregulated in CRC tissues compared to normal tissues, and its expression level was associated with tumor infiltration and tumor-nodule-metastasis (TNM) stage. Furthermore, BVES-AS1 was found to suppress CRC cell proliferation, migration and metastasis both in vitro and in vivo. Mechanistically, BVES-AS1 acted as a sponge for miR-1269a and miR-1269b, thereby regulating SVEP1. Additionally, the silencing of SVEP1 activated the PI3K/AKT pathway.
These results suggest that BVES-AS1 plays a crucial role in the progression of CRC through the miR-1269a/b-SVEP1-PI3K/AKT axis, providing new insights into the therapeutic strategies for CRC.
众多研究表明长链非编码RNA（lncRNA）参与了包括结直肠癌（CRC）在内的多种癌症类型。然而，lncRNA在CRC中的功能和作用机制仍 largely难以捉摸。
本研究旨在探讨lncRNA BVES-AS1在CRC中的功能和机制。
使用定量实时聚合酶链反应（qPCR）在CRC组织和配对的正常样本中验证BVES-AS1的表达水平。随后，在体外和体内研究BVES-AS1在CRC细胞中的生物学功能。采用了多种实验技术，如蛋白质免疫印迹、荧光原位杂交、RNA测序（RNA-seq）、生物素标记的miRNA下拉测定、双荧光素酶报告基因测定和RNA-蛋白质免疫沉淀（RIP）测定，以阐明BVES-AS1的潜在机制。
本研究结果表明，与正常组织相比，BVES-AS1在CRC组织中的表达下调，其表达水平与肿瘤浸润和肿瘤结节转移（TNM）分期相关。此外，发现BVES-AS1在体外和体内均抑制CRC细胞的增殖、迁移和转移。机制上，BVES-AS1作为miR-1269a和miR-1269b的海绵，从而调节SVEP1。此外，SVEP1的沉默激活了PI3K/AKT通路。
这些结果表明，BVES-AS1通过miR-1269a/b-SVEP1-PI3K/AKT轴在CRC进展中起关键作用，为CRC的治疗策略提供了新的见解。
