Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China.
Biosci Rep. 2019 Nov 29;39(11). doi: 10.1042/BSR20180896.
Hepatocellular carcinoma (HCC) has a high recurrence rate and poor clinical outcome after currently used therapies, including radiofrequency ablation. To explore the possible mechanisms for the relapse of HCC, in the present study we focussed on long non-coding RNA (LncRNA), which has been reported to be involved in tumorigenesis. We identified an LncRNA P5848, whose expression level was up-regulated in tumor samples from HCC patients after radiofrequency ablation. As such, we speculated that LncRNA P5848 may play a role in tumor growth. Here we showed that LncRNA P5848, whose up-regulation can lead to HCC cancer cell proliferation and migration. In vitro and in vivo overexpression of LncRNA P5848 promoted cell growth, cell survival, and cell invasion, whereas LncRNA P5848 depletion exerts opposite effects. Mechanistically, we have found that ENO1 was the target of LncRNA P5848. LncRNA P5848 up-regulated the gene and protein expression level of ENO1, promoting tumor growth and cell survival. However, siRNA-mediated knockdown of ENO1 counteracted the effects of LncRNA P5848 on cancer cell growth, cell survival, and migration. Taken together, LncRNA P5848 promotes HCC development by up-regulating ENO1, indicating that LncRNA P5848-ENO1 axis is a potential therapeutic target for the treatment of HCC.
肝细胞癌（HCC）在目前使用的治疗方法（包括射频消融）后复发率高，临床预后差。为了探讨 HCC 复发的可能机制，本研究我们重点关注长链非编码 RNA（LncRNA），已有研究报道其参与肿瘤发生。我们鉴定出一个 LncRNA P5848，其在射频消融后 HCC 患者的肿瘤样本中的表达水平上调。因此，我们推测 LncRNA P5848 可能在肿瘤生长中发挥作用。我们发现 LncRNA P5848 的上调可导致 HCC 癌细胞增殖和迁移。LncRNA P5848 的体外和体内过表达促进了细胞生长、细胞存活和细胞侵袭，而 LncRNA P5848 的耗竭则产生相反的效果。在机制上，我们发现 ENO1 是 LncRNA P5848 的靶基因。LncRNA P5848 上调了 ENO1 的基因和蛋白表达水平，促进了肿瘤生长和细胞存活。然而，ENO1 的 siRNA 介导的敲低抵消了 LncRNA P5848 对癌细胞生长、存活和迁移的影响。综上所述，LncRNA P5848 通过上调 ENO1 促进 HCC 的发展，表明 LncRNA P5848-ENO1 轴是治疗 HCC 的潜在治疗靶点。
