Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Pathology, The Affiliated Children's Hospital of Nanchang University, Nanchang, China.
Chem Biol Drug Des. 2022 Aug;100(2):280-289. doi: 10.1111/cbdd.14063. Epub 2022 May 30.
Micro-RNAs are involved in the occurrence and development of hepatocellular carcinoma (HCC) as potential therapeutic targets for HCC. In this study, we found that miR-27a-3p was highly expressed in HCC, which was associated with lower survival rates of HCC patients. In vivo and in vitro functional experiments confirmed that over-expression or knock-down miR-27a-3p could significantly affect the proliferation ability of HCCLM3 and Huh-7, two HCC cell lines. Ubiquitin-specific protease 46 (USP46) was confirmed as the key target gene of miR-27a-3p in HCC via RNA-seq, quantitative polymerase chain reaction, Western blotting, and luciferase report. When knocking down USP46, the proliferation activity of HCC cells was significantly enhanced, while it was significantly inhibited after over-expressing USP4. Above results suggest that the abnormally over-expressed miR-27a-3p in liver promotes the proliferation of cancer cells and accelerates the development of HCC by targeting inhibition the expression of USP46. Targeting miR-27a-3p may be an effective strategy for prevention and treatment of HCC.
微小 RNA 参与肝细胞癌（HCC）的发生和发展，是 HCC 的潜在治疗靶点。本研究发现 miR-27a-3p 在 HCC 中高表达，与 HCC 患者生存率降低相关。体内外功能实验证实，过表达或敲低 miR-27a-3p 可显著影响 HCCLM3 和 Huh-7 两种 HCC 细胞系的增殖能力。通过 RNA-seq、定量聚合酶链反应、Western blot 和荧光素酶报告实验证实，泛素特异性蛋白酶 46（USP46）是 miR-27a-3p 在 HCC 中的关键靶基因。敲低 USP46 后，HCC 细胞的增殖活性显著增强，而过表达 USP4 后则显著抑制。以上结果提示，肝脏中异常过表达的 miR-27a-3p 通过靶向抑制 USP46 的表达促进癌细胞的增殖，加速 HCC 的发展。靶向 miR-27a-3p 可能是预防和治疗 HCC 的有效策略。
