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长链非编码RNA NRSN2-AS1通过miR-744-5p/PRKX轴促进卵巢癌的发生和发展。

Long non-coding RNA NRSN2-AS1 facilitates tumorigenesis and progression of ovarian cancer via miR-744-5p/PRKX axis.

作者信息

Chen Qian, Xie Jia, Yang Yisi

机构信息

Department of Gynaecology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, P. R. China.

出版信息

Biol Reprod. 2022 Mar 19;106(3):526-539. doi: 10.1093/biolre/ioab212.

Abstract

Newly discovered lncRNA neurensin-2 antisense RNA 1 (NRSN2-AS1) has not been well explored in cancers. Ovarian cancer (OV) is a primary gynecologic cancer worldwide and has the highest mortality rate among gynecologic cancers. Hence, the role and underlying mechanisms of NRSN2-AS1 in OV were worth investigating. According to the results of qantitative real-time polymerase chain reaction, NRSN2-AS1 displayed the remarkably high expression in OV cells, in contrast to human ovarian epithelial cells. Based on online database, the expression level of NRSN2-AS1 was significantly higher in OV tissues than that in normal ovarian tissues. The data from functional experiments indicated that NRSN2-AS1 knockdown inhibited OV cell malignant behaviors in vitro and OV tumor growth in vivo. Moreover, mechanism analysis unveiled that NRSN2-AS1 functioned as a miR-744-5p sponge to regulate PRKX expression in OV cells. The results of TOP/FOP flash and western blot assays suggested that NRSN2-AS1/miR-744-5p/PRKX axis modulated the activity of Wnt/β-catenin signaling pathway. In summary, we validated NRSN2-AS1 functioned as a novel oncogenic lncRNA in OV and elucidated its specific molecular mechanism. This work might advance our understanding of OV and provide evidence for supporting NRSN2-AS1 as a potential biomarker for OV treatment.

摘要

新发现的长链非编码RNA神经介素-2反义RNA 1(NRSN2-AS1)在癌症中的研究尚未充分开展。卵巢癌(OV)是全球主要的妇科癌症,在妇科癌症中死亡率最高。因此,NRSN2-AS1在卵巢癌中的作用及潜在机制值得研究。根据定量实时聚合酶链反应结果,与人类卵巢上皮细胞相比,NRSN2-AS1在卵巢癌细胞中表达显著升高。基于在线数据库,NRSN2-AS1在卵巢癌组织中的表达水平明显高于正常卵巢组织。功能实验数据表明,敲低NRSN2-AS1可抑制卵巢癌细胞的体外恶性行为及体内肿瘤生长。此外,机制分析揭示NRSN2-AS1作为miR-744-5p的海绵体,在卵巢癌细胞中调节PRKX的表达。TOP/FOP荧光素酶报告基因检测和蛋白质免疫印迹分析结果表明,NRSN2-AS1/miR-744-5p/PRKX轴调节Wnt/β-连环蛋白信号通路的活性。总之,我们证实NRSN2-AS1在卵巢癌中作为一种新的致癌长链非编码RNA发挥作用,并阐明了其具体分子机制。这项工作可能会加深我们对卵巢癌的理解,并为支持NRSN2-AS1作为卵巢癌治疗的潜在生物标志物提供证据。

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