环状MEG3通过降低人肝癌干细胞中的Cbf5来抑制端粒酶活性。
CircMEG3 inhibits telomerase activity by reducing Cbf5 in human liver cancer stem cells.
作者信息
Jiang Xiaoxue, Xing Libo, Chen Yingjie, Qin Rushi, Song Shuting, Lu Yanan, Xie Sijie, Wang Liyan, Pu Hu, Gui Xin, Li Tianming, Xu Jie, Li Jiao, Jia Song, Lu Dongdong
机构信息
Shanghai Putuo District People's Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China.
School of Medicine, Tongji University, Shanghai 200092, China.
出版信息
Mol Ther Nucleic Acids. 2020 Nov 17;23:310-323. doi: 10.1016/j.omtn.2020.11.009. eCollection 2021 Mar 5.
Circular RNA (CircRNA) is a newly identified special class of non-coding RNA (ncRNA) that plays an important regulatory role in the progression of certain diseases. Herein, our results indicate that CircMEG3 is downregulated expression and negatively correlated with the expression of telomerase-related gene Cbf5 in human liver cancer. Moreover, CircMEG3 inhibits the growth of human liver cancer stem cells and CircMEG3 inhibits the expression of m6A methyltransferase METTL3 dependent on HULC. Moreover, CircMEG3 inhibits the expression of Cbf5, a component of telomere synthetase H/ACA ribonucleoprotein (RNP; catalyst RNA pseudouracil modification) through METTL3 dependent on HULC. Thereby, CircMEG3 inhibits telomerase activity and shortens telomere lifespan dependent on HULC and Cbf5 in human liver cancer stem cell. Strikingly, increased Cbf5 abrogates the ability of CircMEG3 to inhibit malignant differentiation of human liver cancer stem cells. In summary, these observations provide important basic information for finding effective liver cancer therapeutic targets.
环状RNA（CircRNA）是新发现的一类特殊的非编码RNA（ncRNA），在某些疾病进展中发挥重要调控作用。在此，我们的结果表明，CircMEG3在人类肝癌中表达下调，且与端粒酶相关基因Cbf5的表达呈负相关。此外，CircMEG3抑制人类肝癌干细胞的生长，并且CircMEG3依赖于HULC抑制m6A甲基转移酶METTL3的表达。此外，CircMEG3通过依赖于HULC的METTL3抑制端粒合成酶H/ACA核糖核蛋白（RNP；催化RNA假尿嘧啶修饰）的组分Cbf5的表达。从而，CircMEG3在人类肝癌干细胞中依赖于HULC和Cbf5抑制端粒酶活性并缩短端粒寿命。引人注目的是，Cbf5增加消除了CircMEG3抑制人类肝癌干细胞恶性分化的能力。总之，这些观察结果为寻找有效的肝癌治疗靶点提供了重要的基础信息。
Zotero 插件