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BBOX1-AS1 通过海绵吸附 miR-3940-3p 上调 BIRC5 表达来加速胃癌增殖。

BBOX1-AS1 Accelerates Gastric Cancer Proliferation by Sponging miR-3940-3p to Upregulate BIRC5 Expression.

作者信息

Yang Yan, Yu Qiong, Li Bing, Guan Renzhen, Huang ChangYong, Yang XiuCheng

机构信息

Department of Gastroenterology, Tengzhou Central People's Hospital, No. 181, Xingtan Road, Tengzhou, 277500, Shandong, China.

Department of Pathology, Zaozhuang Mining Group Central Hospital, Zaozhuang, 277000, Shandong, China.

出版信息

Dig Dis Sci. 2021 Apr;66(4):1054-1062. doi: 10.1007/s10620-020-06308-0. Epub 2020 May 11.

Abstract

BACKGROUND

Gastric cancer (GC) is one type of the most general malignancies in the globe. Research increasingly suggests long non-coding RNAs (lncRNAs) exert crucial roles in GC. However, the function of BBOX1-AS1 in GC has not been reported yet, it needs more explorations.

AIMS

The aim of the study is to figure out the role and related regulation mechanism of BBOX1-AS1 in GC.

METHODS

RT-qPCR assay was applied to detect genes expression. The role of BBOX1-AS1 in GC was investigated by cell counting kit-8, colony formation, tunel detection, and western blot assays. The binding ability between miR-3940-3p and BBOX1-AS1 (or BIRC5) by RIP, RNA pull-down and luciferase reporter assays.

RESULTS

The expression of BBOX1-AS1 presented significantly upregulation in GC tissues and cells. Moreover, upregulation of BBOX1-AS1 promoted GC cell proliferation, and inhibited GC cell apoptosis. However, downregulation of BBOX1-AS1 led to opposite results. Furtherly, we discovered that BBOX1-AS1 bound with miR-3940-3p and also negatively regulated miR-3940-3p. Besides, it proved that miR-3940-3p interplayed with BIRC5 and negatively regulated BIRC5. Through rescue experiments, we proved that BIRC5 reversed miR-3940-3p-mediated cell proliferation or apoptosis in BBOX1-AS1-dysregulated GC cells.

CONCLUSIONS

BBOX1-AS1 accelerates GC proliferation by sponging miR-3940-3p to upregulate BIRC5 expression, which may guide a new direction into the therapeutic strategies of GC.

摘要

背景

胃癌(GC)是全球最常见的恶性肿瘤之一。越来越多的研究表明,长链非编码RNA(lncRNAs)在胃癌中发挥着关键作用。然而,BBOX1-AS1在胃癌中的功能尚未见报道,仍需进一步探索。

目的

本研究旨在明确BBOX1-AS1在胃癌中的作用及相关调控机制。

方法

采用RT-qPCR法检测基因表达。通过细胞计数试剂盒-8、集落形成、TUNEL检测和蛋白质免疫印迹分析等实验,研究BBOX1-AS1在胃癌中的作用。运用RIP、RNA下拉和荧光素酶报告基因分析等实验,检测miR-3940-3p与BBOX1-AS1(或BIRC5)之间的结合能力。

结果

BBOX1-AS1在胃癌组织和细胞中的表达显著上调。此外,BBOX1-AS1的上调促进了胃癌细胞的增殖,并抑制了胃癌细胞的凋亡。然而,BBOX1-AS1的下调则导致相反的结果。进一步研究发现,BBOX1-AS1与miR-3940-3p结合,并对miR-3940-3p起负调控作用。此外,还证明miR-3940-3p与BIRC5相互作用,并对BIRC5起负调控作用。通过拯救实验,证明BIRC5可逆转miR-3940-3p介导的BBOX1-AS1失调的胃癌细胞增殖或凋亡。

结论

BBOX1-AS1通过吸附miR-3940-3p上调BIRC5表达,从而促进胃癌增殖,这可能为胃癌的治疗策略提供新的方向。

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