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长链非编码 RNA WWOX-AS1 在肝细胞癌中吸附 miR-20b-5p 并通过上调 WWOX 抑制其进展。

LncRNA WWOX-AS1 sponges miR-20b-5p in hepatocellular carcinoma and represses its progression by upregulating WWOX.

机构信息

Department of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital, Hainan Medical University , Haikou, China.

Geriatrics Center, Hainan General Hospital, Hainan Medical University , Haikou, China.

出版信息

Cancer Biol Ther. 2020 Oct 2;21(10):927-936. doi: 10.1080/15384047.2020.1806689. Epub 2020 Sep 15.

Abstract

Increasing evidence has revealed that long noncoding RNAs (lncRNAs) emerge as pivotal regulators in diverse cancers, including hepatocellular carcinoma (HCC). This study was conducted to investigate the role of lncRNA WWOX antisense RNA 1 (WWOX-AS1) in HCC progression. Our present study illustrated that WWOX-AS1 was lowly expressed in HCC tissues and cell lines. High WWOX-AS1 expression was further confirmed to predict a favorable prognosis in HCC patients. Through functional assays, we observed that upregulated WWOX-AS1 was correlated with decreased cell proliferation, migration, epithelial to mesenchymal transition (EMT) process and increased cell apoptosis, suggesting that WWOX-AS1 exerted anti-carcinogenic role in the development of HCC. Moreover, WWOX, the nearby gene of WWOX-AS1, was found at a low level in HCC tissues and cell lines. Furthermore, there was a positive relationship between WWOX-AS1 and WWOX. Additionally, WWOX overexpression hampered cell proliferation, migration, EMT process and induced cell apoptosis in HCC. Mechanically, WWOX-AS1 was identified as a cytoplasmic RNA in HCC cells and sponged miR-20b-5p to regulate WWOX expression. Rescue assays further indicated that WWOX knockdown counteracted WWOX-AS1 overexpression-mediated suppressive function on HCC progression. Collectively, WWOX-AS1/miR-20b-5p/WWOX axis suppresses HCC tumorigenesis, hinting a potential molecular mechanism for the therapy of HCC patients.

摘要

越来越多的证据表明,长非编码 RNA(lncRNA)在多种癌症中作为关键调节剂出现,包括肝细胞癌(HCC)。本研究旨在探讨 lncRNA WWOX 反义 RNA 1(WWOX-AS1)在 HCC 进展中的作用。我们的研究表明,WWOX-AS1 在 HCC 组织和细胞系中低表达。高 WWOX-AS1 表达进一步证实可预测 HCC 患者的预后良好。通过功能测定,我们观察到上调的 WWOX-AS1 与细胞增殖、迁移、上皮间质转化(EMT)过程减少和细胞凋亡增加相关,表明 WWOX-AS1 在 HCC 的发展中发挥了抗癌作用。此外,WWOX-AS1 附近基因 WWOX 在 HCC 组织和细胞系中低表达。此外,WWOX-AS1 和 WWOX 之间存在正相关关系。此外,WWOX 过表达可阻碍 HCC 细胞的增殖、迁移、EMT 过程并诱导细胞凋亡。机制上,WWOX-AS1 被鉴定为 HCC 细胞中的细胞质 RNA,并通过海绵吸附 miR-20b-5p 来调节 WWOX 的表达。挽救实验进一步表明,WWOX 敲低可拮抗 WWOX-AS1 过表达对 HCC 进展的抑制作用。总之,WWOX-AS1/miR-20b-5p/WWOX 轴抑制 HCC 肿瘤发生,提示了 HCC 患者治疗的潜在分子机制。

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