Department of Radiation Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
Kaohsiung J Med Sci. 2020 Aug;36(8):615-621. doi: 10.1002/kjm2.12209. Epub 2020 Apr 7.
Ubiquitin-specific peptidase 13 (USP13) has been reported to be involved in the tumorigenesis of several tumors, but its function in tumors is still controversial. In this study, the function of USP13 in hepatocellular carcinoma (HCC) was investigated, and we found that USP13 was significantly upregulated in both of primary HCC tumor tissues and cell lines. And HCC patients with high USP13 expression had a shorter overall survival or relapse-free survival than patients with low USP13 expression. In HCC cell lines, knockdown of USP13 by shRNAs markedly decreased HCC cell growth, and mechanistic investigations revealed that USP13 knockdown could markedly downregulate the expression levels of c-Myc. Moreover, overexpression of c-Myc could significantly attenuate the effects of shUSP13 on HCC cell growth inhibition. In addition, in vivo experiments showed that knockdown of USP13 could significantly inhibit xenograft tumor growth of HCC. Taken together, our present study provided the first evidence that USP13 acted as a novel driver in HCC tumorigenesis by regulating c-Myc expression, and targeting USP13 could be a promising strategy for HCC therapy.
泛素特异性肽酶 13（USP13）已被报道参与多种肿瘤的发生，但它在肿瘤中的作用仍存在争议。在这项研究中，我们研究了 USP13 在肝细胞癌（HCC）中的功能，发现 USP13 在原发性 HCC 肿瘤组织和细胞系中均显著上调。并且，USP13 高表达的 HCC 患者的总生存期或无复发生存期短于 USP13 低表达的患者。在 HCC 细胞系中，shRNA 敲低 USP13 可显著降低 HCC 细胞的生长，机制研究表明，USP13 敲低可显著下调 c-Myc 的表达水平。此外，c-Myc 的过表达可显著减弱 shUSP13 对 HCC 细胞生长抑制的影响。此外，体内实验表明，敲低 USP13 可显著抑制 HCC 的异种移植肿瘤生长。总之，本研究首次提供了证据表明，USP13 通过调节 c-Myc 表达在 HCC 肿瘤发生中起新型驱动作用，靶向 USP13 可能是 HCC 治疗的一种有前途的策略。
