Human hepatocellular carcinoma (HCC) is a malignant cancer. It is a challenge to develop anti-HCC drugs due to HCC's extreme aggressiveness and with the sensitivity of the liver to show severe adverse effects. More importantly, the precise mechanisms causing HCC pathogenicity are not known. Our previous study disclosed Nogo-B as a reticulon 4 (Rtn4) family member. In the present study, we first identified that Nogo-B played a critical role in HCC progression. We found, via in vitro and in vivo assays, that Nogo-B was expressed aberrantly in primary HCC tumor tissues and immortal HCC cells but was relatively scarce in the normal liver tissues or cells. Nogo-B knockout, via the CRISPR-Cas9 technique, resulted in significant suppression of HCC cell proliferation and tumor growth. Next-generation sequencing analysis showed that Nogo-B knockout have effects on interleukin-6 (IL-6) signaling pathway. Furthermore, we observed that IL-6 induced phosphorylation of STAT3 (pSTAT3) in wild-type HCC cells, but Nogo-B knockout could reduce IL-6-induced increase of pSTAT3, supporting that Nogo-B affects HCC tumor progression possibly via regulating the IL-6/STAT3 signaling pathway. In conclusion, Nogo-B is expressed aberrantly in HCCs and plays an oncogenic role. These findings support that Nogo-B may be a novel anti-HCC therapeutic target.

中文翻译：

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Nogo-B 基因的敲除可减弱肝细胞癌的肿瘤生长和转移。


人类肝细胞癌（HCC）是一种恶性肿瘤。由于HCC的极端侵袭性以及肝脏对表现出严重不良反应的敏感性，开发抗HCC药物是一个挑战。更重要的是，导致 HCC 致病性的确切机制尚不清楚。我们之前的研究表明 Nogo-B 是 reticulon 4 (Rtn4) 家族成员。在本研究中，我们首先发现 Nogo-B 在 HCC 进展中发挥着关键作用。通过体外和体内测定，我们发现Nogo-B在原发性HCC肿瘤组织和永生性HCC细胞中异常表达，但在正常肝组织或细胞中相对稀少。通过 CRISPR-Cas9 技术敲除 Nogo-B，可显着抑制 HCC 细胞增殖和肿瘤生长。新一代测序分析表明Nogo-B敲除对白细胞介素6（IL-6）信号通路有影响。此外，我们观察到IL-6诱导野生型HCC细胞中STAT3（pSTAT3）的磷酸化，但Nogo-B敲除可以减少IL-6诱导的pSTAT3的增加，支持Nogo-B可能通过调节来影响HCC肿瘤进展IL-6/STAT3 信号通路。总之，Nogo-B 在 HCC 中异常表达并发挥致癌作用。这些发现支持 Nogo-B 可能是一种新型的抗 HCC 治疗靶点。