Department of Surgery, Songshan Hospital of Qingdao University, Qingdao, China.
Kaohsiung J Med Sci. 2020 Jun;36(6):423-428. doi: 10.1002/kjm2.12193. Epub 2020 Feb 13.
MicroRNA-216b (miR-216b) has been reported to be downregulated in several tumors, its mechanism is still little-studied in hepatocellular carcinoma (HCC). In the present study, we found that miR-216b was downregulated in HCC, but Ubiquitin-specific peptidase 28 (USP28) was upregulated. In addition, Kaplan-Meier-plotter analysis indicated that liver cancer patients with high miR-216b expression had a longer overall survival, but patients with high USP28 had a shorter overall survival. Further studies showed that overexpression of miR-216b inhibited HCC cell growth, and molecular investigations revealed that miR-216b targeted USP28 and inhibited its expression in HCC cells. In addition, overexpression of miR-216b suppressed the substrates' expression of USP28, for example, c-Myc, and miR-216b overexpression also inhibited Cyclin E expression as well as upregulating p27 expression, both of which were the downstream signals of c-Myc. These results indicated that miR-216b downregulated USP28/c-Myc signaling in HCC cells. Collectively, this study demonstrated that miR-216b/c-Myc axis could be as a potential target for HCC therapy in the future.
微小 RNA-216b（miR-216b）在几种肿瘤中表达下调，但其在肝细胞癌（HCC）中的作用机制仍研究较少。本研究发现 miR-216b 在 HCC 中表达下调，而泛素特异性肽酶 28（USP28）表达上调。此外，Kaplan-Meier-plotter 分析表明，miR-216b 高表达的肝癌患者总生存期较长，而 USP28 高表达的患者总生存期较短。进一步的研究表明，miR-216b 的过表达抑制 HCC 细胞的生长，分子研究表明 miR-216b 靶向 USP28 并抑制其在 HCC 细胞中的表达。此外，miR-216b 的过表达抑制了 USP28 的底物表达，例如 c-Myc，miR-216b 的过表达还抑制了 Cyclin E 的表达并上调了 p27 的表达，这两者都是 c-Myc 的下游信号。这些结果表明 miR-216b 在 HCC 细胞中下调了 USP28/c-Myc 信号通路。总之，本研究表明 miR-216b/c-Myc 轴可能成为未来 HCC 治疗的潜在靶点。
