Department of General Surgery, The First People's Hospital of Qujing , Qujing, People's Republic of China.
Department of Anesthesiology, The First People's Hospital of Qujing , Qujing, People's Republic of China.
Cancer Biol Ther. 2020 Dec 1;21(12):1145-1153. doi: 10.1080/15384047.2020.1840886. Epub 2020 Nov 12.
A cornucopia of literatures has characterized the involvement of a host of functional molecules in liver cancer. Herein, according to online datasets, we found that cytochrome P450 family 2 subfamily C member 8 (CYP2C8) was downregulated in liver cancer, and high CYP2C8 expression was associated with favorable overall survival. Lower levels of CYP2C8 were confirmed in liver cancer cells. CYP2C8 overexpression efficiently attenuated liver cancer cell proliferation and promoted apoptosis. We then discovered that miR-382-3p directly targeted CYP2C8 to inhibit its expression in liver cancer cells based on bioinformatic prediction and experimental confirmation. Moreover, a cytoplasmic long noncoding RNA (lncRNA), growth arrest-specific 5 (GAS5), sponged and down-regulated miR-382-3p, thus positively modulating CYP2C8 expression. Rescue assays indicated that GAS5 overexpression gave rise to decreased proliferation and increased apoptosis of liver cancer cells, while CYP2C8 knockdown counteracted GAS5-mediated anti-carcinogenic effects. In summary, our work offered a solid experimental foundation for understanding the functional role of CYP2C8 and the mechanism of GAS5/miR-382-3p/CYP2C8 axis in cell proliferation and apoptosis of liver cancer.
大量文献表明，许多功能分子参与了肝癌的发生。在此，我们根据在线数据集发现，细胞色素 P450 家族 2 亚家族 C 成员 8（CYP2C8）在肝癌中下调，高 CYP2C8 表达与良好的总生存率相关。肝癌细胞中 CYP2C8 的水平较低。CYP2C8 的过表达可有效抑制肝癌细胞的增殖并促进凋亡。然后，我们发现基于生物信息学预测和实验验证，miR-382-3p 可直接靶向 CYP2C8 抑制其在肝癌细胞中的表达。此外，细胞质长非编码 RNA（lncRNA）生长停滞特异性基因 5（GAS5）可吸附并下调 miR-382-3p，从而正向调节 CYP2C8 的表达。挽救实验表明，GAS5 的过表达导致肝癌细胞增殖减少和凋亡增加，而 CYP2C8 的敲低则抵消了 GAS5 介导的抗癌作用。总之，我们的工作为理解 CYP2C8 的功能作用以及 GAS5/miR-382-3p/CYP2C8 轴在肝癌细胞增殖和凋亡中的机制提供了坚实的实验基础。
