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黄芩素通过下调长链非编码 RNA BDLNR 及其下游 PI3K/Akt 通路抑制宫颈癌进展。

Baicalein inhibits cervical cancer progression via downregulating long noncoding RNA BDLNR and its downstream PI3K/Akt pathway.

机构信息

Department of Obstetrics and Gynecology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.

Experimental Medicine Center, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.

出版信息

Int J Biochem Cell Biol. 2018 Jan;94:107-118. doi: 10.1016/j.biocel.2017.11.009. Epub 2017 Nov 23.

Abstract

Baicalein, an active flavonoid extracted from the root of Scutellaria baicalensis Georgi, has fascinating anti-cancer effects on many cancers. Our previous study also found that baicalein inhibited cervical cancer cell proliferation and migration, and induced cervical cancer cell apoptosis and cell cycle arrest. However, the molecular mechanisms underlying the anti-cancer effects of baicalein are largely unknown. In this study, we identified a novel long noncoding RNA (lncRNA), which is downregulated by baicalein in a dose- and time-dependent manner in cervical cancer. We named this lncRNA as baicalein down-regulated long noncoding RNA (BDLNR). Gain-of- and loss-of-function assays showed that BDLNR was required for baicalein-induced cell proliferation inhibition, cell death induction, migration inhibition, and in vivo tumor growth inhibition of cervical cancer. Mechanistically, BDLNR physically bound to YBX1, recruited YBX1 to PIK3CA promoter, activated PIK3CA expression and PI3K/Akt pathway. Furthermore, BDLNR was upregulated in cervical cancer and associated with poor prognosis of cervical cancer patients. Collectively, our data demonstrated that BDLNR mediated the anti-cancer effects of baicalein in cervical cancer via activating PI3K/Akt pathway, and implied that BDLNR would be potential therapeutic target for enhancing the anti-cancer effects of baicalein in cervical cancer.

摘要

黄芩素是从黄芩根中提取的一种活性黄酮类化合物,对许多癌症具有令人着迷的抗癌作用。我们之前的研究还发现,黄芩素抑制宫颈癌细胞增殖和迁移,并诱导宫颈癌细胞凋亡和细胞周期停滞。然而,黄芩素抗癌作用的分子机制在很大程度上尚不清楚。在这项研究中,我们鉴定了一种新型的长非编码 RNA(lncRNA),其在宫颈癌中呈剂量和时间依赖性地下调黄芩素的表达。我们将这种 lncRNA 命名为黄芩素下调的长非编码 RNA(BDLNR)。增益和失活功能试验表明,BDLNR 是黄芩素诱导的宫颈癌细胞增殖抑制、细胞死亡诱导、迁移抑制和体内肿瘤生长抑制所必需的。从机制上讲,BDLNR 与 YBX1 结合,将 YBX1 募集到 PIK3CA 启动子上,激活 PIK3CA 的表达和 PI3K/Akt 通路。此外,BDLNR 在宫颈癌中上调,并与宫颈癌患者的不良预后相关。综上所述,我们的数据表明,BDLNR 通过激活 PI3K/Akt 通路介导黄芩素在宫颈癌中的抗癌作用,并暗示 BDLNR 可能成为增强黄芩素在宫颈癌中抗癌作用的潜在治疗靶点。

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