Department of General Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510000, PR China.
Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510000, PR China.
Biomed Pharmacother. 2018 Aug;104:102-109. doi: 10.1016/j.biopha.2018.05.006. Epub 2018 May 15.
Dysregulation of long non-coding RNAs is a newly identified mechanism for tumour progression. Previous studies have suggested that the nuclear factor of activated T cells (NFAT) gene plays a very important role in cancer growth and metastasis. However, lncNRON is a newly identified repressor of NFAT, and its function is largely unknown, especially in hepatocellular carcinoma (HCC). Therefore, the expression levels of lncNRON in 215 pairs of HCC tissue were evaluated by qRT-PCR, and its relationship to clinicopathological parameters, recurrence, and survival was analysed. Furthermore, stably overexpressing lncNRON cell lines were constructed and evaluated for cell phenotype. Finally, we detected epithelial-to-mesenchymal transition (EMT) proteins to determine the underlying mechanism involved in lncNRON function. We observed that lncNRON was downregulated in HCC tumour tissues; low lncNRON expression was associated with poor tumour differentiation and the presence of vascular tumour thrombus, which tended to result in poor clinical outcomes, as demonstrated by the recurrence rate and survival curves. Functional analysis showed that lncNRON overexpression impaired colony formation and cell viability and inhibited cell migration and invasion. A study using tumour-bearing mice showed that lncNRON markedly limited tumour growth and lung metastasis in vivo. Importantly, western blot analysis revealed that the expression of the EMT-related epithelial marker, E-cadherin, increased, whereas the expression of mesenchymal markers N-cadherin, snail, and vimentin was attenuated by lncNRON overexpression in HCC cells. Therefore, lower lncNRON expression indicates a poorer clinical outcome in HCC. LncNRON overexpression can suppress HCC growth and metastasis via inhibiting the EMT, and lncNRON may function as a new HCC prognostic marker.
长链非编码 RNA 失调是肿瘤进展的一种新发现的机制。先前的研究表明，激活的 T 细胞核因子（NFAT）基因在癌症生长和转移中起着非常重要的作用。然而，lncNRON 是 NFAT 的一种新发现的抑制剂，其功能在很大程度上尚不清楚，特别是在肝细胞癌（HCC）中。因此，通过 qRT-PCR 评估了 215 对 HCC 组织中 lncNRON 的表达水平，并分析了其与临床病理参数、复发和生存的关系。此外，构建了稳定过表达 lncNRON 的细胞系，并对其细胞表型进行了评估。最后，我们检测了上皮间质转化（EMT）蛋白，以确定 lncNRON 功能所涉及的潜在机制。我们观察到 lncNRON 在 HCC 肿瘤组织中下调；低表达 lncNRON 与肿瘤分化差和血管肿瘤血栓存在相关，这倾向于导致不良的临床结果，这可以从复发率和生存曲线中得到证明。功能分析表明，lncNRON 过表达可损害集落形成和细胞活力，并抑制细胞迁移和侵袭。使用荷瘤小鼠的研究表明，lncNRON 在体内显著限制了肿瘤生长和肺转移。重要的是，Western blot 分析显示，E-cadherin 等 EMT 相关上皮标志物的表达增加，而 N-cadherin、snail 和 vimentin 等间充质标志物的表达在 HCC 细胞中被 lncNRON 过表达所减弱。因此，lncNRON 表达较低表明 HCC 的临床预后较差。lncNRON 过表达可通过抑制 EMT 来抑制 HCC 的生长和转移，lncNRON 可能是 HCC 的一种新的预后标志物。
