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，长链非编码 RNA (lncRNA) 成为多种癌症的关键调节因子，包括肝细胞癌 (HCC)。本研究旨在研究 lncRNA WWOX 反义 RNA 1 (WWOX-AS1) 在 HCC 进展中的作用。我们目前的研究表明 WWOX-AS1 在 HCC 组织和细胞系中低表达。进一步证实高 WWOX-AS1 表达可预测 HCC 患者的良好预后。通过功能分析，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 的发展中发挥抗癌作用。此外，WWOX-AS1 的邻近基因 WWOX 在 HCC 组织和细胞系中的含量较低。此外，WWOX-AS1 和 WWOX 之间存在正相关关系。此外，WWOX 过表达阻碍了 HCC 中的细胞增殖、迁移、EMT 过程并诱导细胞凋亡。从机制上讲，WWOX-AS1 被鉴定为 HCC 细胞中的细胞质 RNA，并吸附 miR-20b-5p 以调节 WWOX 表达。救援分析进一步表明，WWOX 敲低抵消了 WWOX-AS1 过表达介导的对 HCC 进展的抑制功能。总的来说，WWOX-AS1/miR-20b-5p/WWOX 轴抑制 HCC 肿瘤发生，暗示了治疗 HCC 患者的潜在分子机制。WWOX-AS1 被鉴定为 HCC 细胞中的细胞质 RNA，并吸附 miR-20b-5p 以调节 WWOX 表达。救援分析进一步表明，WWOX 敲低抵消了 WWOX-AS1 过表达介导的 HCC 进展抑制功能。总的来说，WWOX-AS1/miR-20b-5p/WWOX 轴抑制 HCC 肿瘤发生，暗示了治疗 HCC 患者的潜在分子机制。WWOX-AS1 被鉴定为 HCC 细胞中的细胞质 RNA，并吸附 miR-20b-5p 以调节 WWOX 表达。救援分析进一步表明，WWOX 敲低抵消了 WWOX-AS1 过表达介导的对 HCC 进展的抑制功能。总的来说，WWOX-AS1/miR-20b-5p/WWOX 轴抑制 HCC 肿瘤发生，暗示了治疗 HCC 患者的潜在分子机制。