MiR‐27a‐3p targets USP46 to inhibit the cell proliferation of hepatocellular carcinoma
MiR‐27a‐3p targets USP46 to inhibit the cell proliferation of hepatocellular carcinoma
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DOI：
10.1111/cbdd.14063
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发表时间：
2022-05
影响因子：
3
通讯作者：
Minghua Wen;Hongyan Xu;Hong-Qi Peng;Yanling Sheng;Wenlong Yang;Jinlong Yan
中科院分区：
文献类型：
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作者：
Minghua Wen;Hongyan Xu;Hong-Qi Peng;Yanling Sheng;Wenlong Yang;Jinlong Yan
作为肝细胞癌潜在的治疗靶点，microRNAs参与了肝细胞癌的发生发展。在本研究中，我们发现miR-27A-3p在肝细胞癌中高表达，这与肝细胞癌患者较低的生存率有关。体内和体外功能实验证实，miR-27A-3p的过表达或下调可显著影响HCCLM3和Huh-7这两个肝癌细胞系的增殖能力。通过RNA-SEQ、定量聚合酶链式反应、Western blotting和荧光素酶报道，证实泛素特异性蛋白水解酶46(USP46)是miR-27A-3p在肝癌中的关键靶基因。当USP46被敲除时，肝癌细胞的增殖活性被显著增强，而过表达USP4后，其增殖活性被显著抑制。以上结果提示，miR-27A-3p在肝脏中异常过表达，通过靶向抑制USP46的表达，促进癌细胞的增殖，加速肝癌的发展。靶向miR-27A-3p可能是预防和治疗肝癌的有效策略。
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.