关键词: BVES-AS1 PI3K/AKT SVEP1 colorectal cancer miRNA

来  源:   DOI:10.17219/acem/175050

Abstract:
BACKGROUND: 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.
OBJECTIVE: The aim of this study was to explore the function and mechanism of lncRNA BVES-AS1 in CRC.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要:
背景:许多研究表明长链非编码RNA(lncRNA)参与各种癌症类型,包括结直肠癌(CRC)。然而,lncRNAs在CRC中的功能和机制作用在很大程度上仍然难以捉摸。
目的:本研究旨在探讨lncRNABVES-AS1在CRC中的作用及机制。
方法:使用定量实时聚合酶链反应(qPCR)在CRC组织和配对正常样本中验证BVES-AS1的表达水平。在体外和体内研究了BVES-AS1在CRC细胞中的生物学功能。各种实验技术,如蛋白质印迹,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-蛋白免疫沉淀(RIP)分析用于阐明BVES-AS1的潜在机制。
结果:这项研究的结果表明,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)分期有关。此外,发现BVES-AS1抑制CRC细胞增殖,体内和体外的迁移和转移。机械上,BVES-AS1充当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。
结论:这些结果表明,BVES-AS1通过miR-1269a/b-SVEP1-PI3K/AKT轴在CRC进展中发挥关键作用,为CRC的治疗策略提供新的见解。
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