Chen Qian, Xie Jia, Yang Yisi
Department of Gynaecology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, P. R. China.
Biol Reprod. 2022 Mar 19;106(3):526-539. doi: 10.1093/biolre/ioab212.
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.
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。