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The effect of BACE1-AS on β-amyloid generation by regulating BACE1 mRNA expression.
BMC Molecular Biology ( IF 4.619 ) Pub Date : 2019-10-01 , DOI: 10.1186/s12867-019-0140-0
Fan Li 1 , Yun Wang 1 , Hui Yang 1 , Yingying Xu 1 , Xiaoyan Zhou 1 , Xiao Zhang 1 , Zhaohong Xie 1 , Jianzhong Bi 1
Affiliation  

The BACE1 antisense transcript (BACE1-AS) is a conserved long noncoding RNA (lncRNA). The level of BACE1-AS is significantly increased and the level of the BACE1 mRNA is slightly increased in subjects with AD. BACE1-AS exerts a significant moderating effect on the expression of the BACE1 mRNA and promotes the formation of Aβ. After the administration of Aβ1-42 to SH-SY5Y cells and C57/BL6J mice, we detected the expression of BACE1-AS, BACE1 mRNA, and BACE1 protein, as well as the concentration of Aβ1-40. Then, we silenced the expression of BACE1-AS in SH-SY5Y and 20E2 cells using siRNAs targeting BACE1-AS and detected its effects on the levels of the BACE1 mRNA and BACE1 protein and Aβ1-40 generation. The administration of Aβ1-42 increased the expression of BACE1-AS, BACE1 mRNA and protein, as well as the concentration of Aβ1-40 in SH-SY5Y cells and the brains of C57BL/6J mice. Pretreatment with the BACE1-AS siRNA inhibited the effect of Aβ1-42 on increasing the expression of BACE1-AS and BACE1, as well as the generation of Aβ. The mechanism by which exogenous Aβ1-42 induces BACE1 expression and Aβ generation is mediated by BACE1-AS. BACE1-AS is involved in the mechanism regulating BACE1 expression and Aβ generation in APPsw transgenic cells.

中文翻译:

BACE1-AS通过调节BACE1 mRNA表达对β-淀粉样蛋白生成的影响。

BACE1反义转录物(BACE1-AS)是一个保守的长非编码RNA(lncRNA)。在患有AD的受试者中,BACE1-AS的水平显着升高,而BACE1 mRNA的水平略有升高。BACE1-AS对BACE1 mRNA的表达具有明显的调节作用,并促进Aβ的形成。在对SH-SY5Y细胞和C57 / BL6J小鼠施用Aβ1-42后,我们检测到BACE1-AS,BACE1 mRNA和BACE1蛋白的表达以及Aβ1-40的浓度。然后,我们使用靶向BACE1-AS的siRNA沉默了SH-SY5Y和20E2细胞中BACE1-AS的表达,并检测了其对BACE1 mRNA和BACE1蛋白水平以及Aβ1-40产生的影响。施用Aβ1-42可增加BACE1-AS,BACE1 mRNA和蛋白的表达,以及C57BL / 6J小鼠的SH-SY5Y细胞和大脑中Aβ1-40的浓度。用BACE1-AS siRNA进行预处理可抑制Aβ1-42对增加BACE1-AS和BACE1表达以及Aβ生成的影响。外源性Aβ1-42诱导BACE1表达和Aβ生成的机制是由BACE1-AS介导的。BACE1-AS参与调节APPsw转基因细胞中BACE1表达和Aβ生成的机制。
更新日期:2019-10-01
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