Zhou Li, Hao Jin, Yuan Yue, Peng Rui, Wang Honglian, Ni Dongsheng, Gu Yuping, Huang Liyuan, Mao Zhaomin, Lyu Zhongshi, Du Yao, Liu Zhicheng, Li Yiman, Ju Pan, Long Yaoshui, Liu Jianing, Zhou Qin
The Division of Molecular Nephrology and the Creative Training Center for Undergraduates, The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
Laboratory of Organ Fibrosis Prophylaxis and Treatment by Combine Traditional Chinese and Western Medicine, Research Center of Combine Traditional Chinese and Western Medicine, Affiliated Traditional Medicine Hospital of Sichuan Medical University, Luzhou 646000, China.
Int J Mol Sci. 2016 May 25;17(6):811. doi: 10.3390/ijms17060811.
Apobec-1 complementation factor (A1CF) is a heterogeneous nuclear ribonuceloprotein (hnRNP) and mediates apolipoprotein-B mRNA editing. A1CF can promote the regeneration of the liver by post-transcriptionally stabilizing Interleukin-6 (IL-6) mRNA. It also contains two transcriptional variants-A1CF64 and A1CF65, distinguished by the appearance of a 24-nucleotide motif which contributes to the corresponding eight-amino acid motif of EIYMNVPV. For the first time, we demonstrated that the EIYMNVPV motif was essential for A1CF nucleus localization, A1CF deficient of the EIYMNVPV motif, A1CF (-8aa) showed cytoplasm distribution. More importantly, we found that A1CF (-8aa), but not its full-length counterpart, can promote proliferation of MDA-MB-231 cells accompanied with increased level of IL-6 mRNA. Furthermore, silencing of IL-6 attenuated A1CF (-8aa)-induced proliferation in MDA-MB-231 cells. In conclusion, notably, these findings suggest that A1CF (-8aa) promoted proliferation of MDA-MB-231 cells in vitro viewing IL-6 as a target. Thus, the EIYMNVPV motif could be developed as a potential target for basal-like breast cancer therapy.
载脂蛋白B mRNA编辑酶催化多肽1互补因子（A1CF）是一种不均一核核糖核蛋白（hnRNP），介导载脂蛋白B mRNA的编辑。A1CF可通过转录后稳定白细胞介素-6（IL-6）mRNA来促进肝脏再生。它还包含两种转录变体——A1CF64和A1CF65，区别在于出现了一个24个核苷酸的基序，该基序对应于EIYMNVPV的相应八个氨基酸基序。我们首次证明，EIYMNVPV基序对A1CF的细胞核定位至关重要，缺乏EIYMNVPV基序的A1CF，即A1CF（-8aa），表现出细胞质分布。更重要的是，我们发现A1CF（-8aa）而非其全长对应物可促进MDA-MB-231细胞增殖，同时IL-6 mRNA水平升高。此外，沉默IL-6可减弱A1CF（-8aa）诱导的MDA-MB-231细胞增殖。总之，值得注意的是，这些发现表明A1CF（-8aa）在体外以IL-6为靶点促进了MDA-MB-231细胞的增殖。因此，EIYMNVPV基序可被开发为基底样乳腺癌治疗的潜在靶点。
