LncRNA BACE1-AS Accelerates the Progression of Gastric Cancer Through Regulating as a ceRNA of miR-422a to Positively Control BRD4 Expression

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
Wei Cao, Yang Yang, Xiaosong Wei, Weichang Chen
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Abstract

Gastric cancer (GC) is a leading global cause of cancer-related mortality, necessitating urgent research on its pathogenesis, prevention, and treatment. In this study, we investigated the expressions of LncRNA BACE1-AS, mRNA BRD4, and miR-422a in GES-1 and GC cells under various treatments using RT-PCR. Western Blots confirmed protein expressions in HGC-27 and SNU-1 cells. EDU and MTT assays assessed cell proliferation, while Transwell tests determined invasion capacity, and flow cytometry analyzed apoptosis. BACE1-AS and BRD4 were significantly elevated in cancerous tissues compared to paired non-cancerous tissues. BACE1-AS knockdown inhibited invasion and proliferation, promoting apoptosis. miR-422a mimics suppressed proliferation and invasion while enhancing apoptosis, and miR-422a mimics with BRD4 overexpression had the opposite effect. Moreover, BAX protein increased in the si-BACE1-AS group but decreased in the si-BACE1-AS+miR-422a inhibitor group. Si-BACE1-AS and miR-422a mimics reduced the expression of C-Myc, CyclinD1, Survivin, CDK4, and Bcl-2, while the si-BACE1-AS+miR-422a inhibitor and miR-422a mimics+BRD4-OV groups showed the opposite trend. Our findings suggest that LncRNA BACE1-AS positively regulates gastric cancer progression by modulating BRD4 as a competitive endogenous RNA for miR-422a. This LncRNA BACE1-AS/BRD4/miR-422a signaling axis presents potential targets for developing therapeutic strategies against gastric cancer.
LncRNA BACE1-AS 作为 miR-422a 的 ceRNA 积极控制 BRD4 的表达,从而加速胃癌的进展
胃癌(GC)是全球癌症相关死亡的主要原因之一,因此对其发病机制、预防和治疗的研究迫在眉睫。在这项研究中,我们利用 RT-PCR 技术研究了 LncRNA BACE1-AS、mRNA BRD4 和 miR-422a 在 GES-1 和 GC 细胞中的表达情况。Western 印迹证实了 HGC-27 和 SNU-1 细胞中蛋白质的表达。EDU和MTT试验评估了细胞增殖,Transwell试验测定了侵袭能力,流式细胞术分析了细胞凋亡。与配对的非癌组织相比,癌组织中的BACE1-AS和BRD4明显升高。miR-422a模拟物抑制增殖和侵袭,同时增强细胞凋亡,而BRD4过表达的miR-422a模拟物则有相反的作用。此外,Si-BACE1-AS组的BAX蛋白增加,而Si-BACE1-AS+miR-422a抑制剂组的BAX蛋白减少。Si-BACE1-AS和miR-422a模拟物降低了C-Myc、CyclinD1、Survivin、CDK4和Bcl-2的表达,而si-BACE1-AS+miR-422a抑制剂组和miR-422a模拟物+BRD4-OV组则呈现出相反的趋势。我们的研究结果表明,LncRNA BACE1-AS通过调节作为miR-422a竞争性内源RNA的BRD4来积极调控胃癌的进展。LncRNA BACE1-AS/BRD4/miR-422a 信号轴为开发胃癌治疗策略提供了潜在靶点。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
期刊介绍: ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.
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