microRNA-454 通过调控 SOCS6 促进肝癌起始细胞的扩增。
microRNA-454 promotes liver tumor-initiating cell expansion by regulating SOCS6.
机构信息
Hepato-pancreato-biliary Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
Department of Surgical Oncology, The Bayi Hospital, Nanjing University of Chinese Medicine, Nanjing, China.
出版信息
Exp Cell Res. 2020 May 1;390(1):111955. doi: 10.1016/j.yexcr.2020.111955. Epub 2020 Mar 9.
Tumor-initiating cells (T-ICs) are involved in the tumorigenesis, progression, drug resistance and recurrence of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver T-ICs remains unclear. Herein, we find that miR-454 is upregulated in liver T-ICs and has an important function in liver T-ICs. Functional studies have revealed that knockdown of miR-454 inhibits liver T-IC self-renewal and tumorigenesis. Conversely, forced miR-454 expression promotes liver T-IC self-renewal and tumorigenesis. Mechanistically, we found that miR-454 downregulates SOCS6 expression in liver T-ICs. The correlation between miR-454 and SOCS6 is validated in human HCC tissues. Furthermore, HCC cells that overexpress miR-454 are resistant to sorafenib treatment. Analysis of patient-derived xenografts (PDXs) further demonstrates that miR-454 may predict sorafenib benefits in HCC patients. In conclusion, our findings reveal the crucial role of miR-454 in liver T-IC expansion and sorafenib response.
肿瘤起始细胞（T-ICs）参与肝癌（HCC）的发生、发展、耐药和复发。然而，肝 T-IC 增殖的潜在机制尚不清楚。在此，我们发现 miR-454 在肝 T-IC 中上调，并在肝 T-IC 中具有重要功能。功能研究表明，miR-454 的敲低抑制肝 T-IC 的自我更新和致瘤性。相反，强制表达 miR-454 促进肝 T-IC 的自我更新和致瘤性。在机制上，我们发现 miR-454 下调肝 T-IC 中的 SOCS6 表达。miR-454 和 SOCS6 之间的相关性在人 HCC 组织中得到验证。此外，过表达 miR-454 的 HCC 细胞对索拉非尼治疗有耐药性。对患者来源的异种移植（PDXs）的分析进一步表明，miR-454 可能预测 HCC 患者对索拉非尼的获益。总之，我们的研究结果揭示了 miR-454 在肝 T-IC 扩增和索拉非尼反应中的关键作用。
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