Hepatocellular carcinoma (HCC) remains one of the most common and aggressive human cancers worldwide. Accumulating evidences indicate that non-coding RNAs are critical regulators implicated in various physiological processes including HCC development. Long non-coding RNA (lncRNA) MYCN opposite-strand (MYCNOS) was reported to be up-regulated in several human cancers, yet its role in HCC progression is still elusive. In the present study, MYCNOS was up-regulated in both HCC tissues and cell lines, and elevated MYCNOS expression was correlated to shorter survival time of HCC patients. We knocked down MYCNOS expression using short hairpin RNAs specifically targeting MYCNOS. MYCNOS knockdown significantly inhibited proliferation in HCC cells in vitro accompanied by exacerbated cell apoptosis; it also suppressed tumor growth in mouse model in vivo. Besides, the migration and invasion of HCC cells were remarkably inhibited after MYCNOS knockdown. In addition, MYCNOS acted as a negative regulator of miR-340 in HCC cells, and all effects of MYCNOS knockdown were abrogated by further miR-340 inhibition. We also discovered that oncogene phosphatidylinositol-3, 4, 5-trisphosphate-dependent Rac exchange factor 2 (PREX2) was a downstream target of miR-340, and PREX2 expression was positively correlated to that of MYCNOS in HCC tissues. In conclusion, our findings demonstrated that MYCNOS knockdown inhibited HCC progression through regulating miR-340.

中文翻译：

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LncRNA MYCNOS通过调节miR-340促进肝细胞癌的增殖和侵袭。

肝细胞癌（HCC）仍然是全球范围内最常见，最具侵略性的人类癌症之一。越来越多的证据表明，非编码RNA是涉及包括HCC发生在内的各种生理过程的关键调控因子。据报道，长非编码RNA（lncRNA）MYCN反向链（MYCNOS）在几种人类癌症中均被上调，但其在HCC进展中的作用仍然难以捉摸。在本研究中，MYCNOS在肝癌组织和细胞系中均上调，而MYCNOS表达的升高与肝癌患者生存时间的缩短有关。我们使用专门针对MYCNOS的短发夹RNA敲低了MYCNOS的表达。MYCNOS敲低显着抑制体外HCC细胞的增殖，并加剧细胞凋亡。它还在体内抑制了小鼠模型中的肿瘤生长。此外，MYCNOS敲低后，HCC细胞的迁移和侵袭被显着抑制。另外，MYCNOS充当HCC细胞中miR-340的负调节剂，并且进一步抑制miR-340消除了MYCNOS敲低的所有作用。我们还发现癌基因磷脂酰肌醇-3、4、5-三磷酸依赖的Rac交换因子2（PREX2）是miR-340的下游靶标，并且PREX2表达与HCC组织中MYCNOS的表达呈正相关。总之，我们的发现表明，MYCNOS的抑制通过调节miR-340抑制了HCC的进程。我们还发现癌基因磷脂酰肌醇-3、4、5-三磷酸依赖的Rac交换因子2（PREX2）是miR-340的下游靶标，并且PREX2表达与HCC组织中MYCNOS的表达呈正相关。总之，我们的发现表明，MYCNOS基因敲低通过调节miR-340抑制了HCC进程。我们还发现癌基因磷脂酰肌醇-3、4、5-三磷酸依赖的Rac交换因子2（PREX2）是miR-340的下游靶标，并且PREX2表达与HCC组织中MYCNOS的表达呈正相关。总之，我们的发现表明，MYCNOS基因敲低通过调节miR-340抑制了HCC进程。