Knockout of the Nogo-B Gene Attenuates Tumor Growth and Metastasis in Hepatocellular Carcinoma.

Abstract

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.

• Authors: Bo Zhu, Shaobo Chen, Xiaoding Hu, Xiaofeng Jin, Yichen Le, Lihuan Cao, Zhonghua Yuan, Zhen Lin, Songmin Jiang, Lichun Sun, Long Yu
• Journal: Neoplasia (New York, N.Y.) (Neoplasia) Vol. 19 Issue 7 Pg. 583-593 (Jul 2017) ISSN: 1476-5586 [Electronic] United States
• PMID: 28628795 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Nogo Proteins
• STAT3 Transcription Factor

Topics

• Adult
• Aged
• Animals
• Carcinoma, Hepatocellular (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation
• Disease Models, Animal
• Disease Progression
• Female
• Gene Expression
• Gene Knockout Techniques
• Heterografts
• Humans
• Liver Neoplasms (genetics, metabolism, pathology)
• Male
• Mice
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging
• Nogo Proteins (genetics, metabolism)
• Phosphorylation
• STAT3 Transcription Factor (metabolism)
• Tumor Burden