EIYMNVPV Motif is Essential for A1CF Nucleus Localization and A1CF (-8aa) Promotes Proliferation of MDA-MB-231 Cells via Up-Regulation of IL-6

Li Zhou; Jin Hao; Yue Yuan; Rui Peng; Honglian Wang; Dongsheng Ni; Yuping Gu; Liyuan Huang; Zhaomin Mao; Zhongshi Lyu; Yao Du; Zhicheng Liu; Yiman Li; Pan Ju; Yaoshui Long; Jianing Liu; Qin Zhou

doi:10.3390/ijms17060811

EIYMNVPV Motif is Essential for A1CF Nucleus Localization and A1CF (-8aa) Promotes Proliferation of MDA-MB-231 Cells via Up-Regulation of IL-6

Int J Mol Sci. 2016 May 25;17(6):811. doi: 10.3390/ijms17060811.

Authors

Li Zhou¹, Jin Hao², Yue Yuan³, Rui Peng⁴, Honglian Wang⁵, Dongsheng Ni⁶, Yuping Gu⁷, Liyuan Huang⁸, Zhaomin Mao⁹, Zhongshi Lyu¹⁰, Yao Du¹¹, Zhicheng Liu¹², Yiman Li¹³, Pan Ju¹⁴, Yaoshui Long¹⁵, Jianing Liu¹⁶, Qin Zhou¹⁷

Affiliations

¹ 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. shmily525520@sina.com.
² 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. lanyxiu@163.com.
³ 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. yyokyy1126@hotmail.com.
⁴ 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. pengrui911@foxmail.com.
⁵ 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. hackie_wang@126.com.
⁶ 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. cqmunds@163.com.
⁷ 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. guyupinglittle@sina.com.
⁸ 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. lyhuang0603@sina.com.
⁹ 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. mao1204086118@163.com.
¹⁰ 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. Zhongshilyu@163.com.
¹¹ 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. duyao_steve@163.com.
¹² 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. liuzhicheng323@163.com.
¹³ 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. 18715854036@sina.cn.
¹⁴ 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. 18883936591@163.com.
¹⁵ 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. lys960110@sina.com.
¹⁶ 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. keithljn@sina.cn.
¹⁷ 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. zhouqin@cqmu.edu.cn.

Abstract

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.

Keywords: Apobec-1 complementation factor (A1CF); EIYMNVPV motif; Interleukin-6 (IL-6); MDA-MB-231 cells; nucleus localization; proliferation.

MeSH terms

Amino Acid Motifs
Animals
Cell Line, Tumor
Cell Nucleus / metabolism*
Cell Proliferation
Cytoplasm / metabolism
Dogs
Humans
Interleukin-6 / genetics*
Madin Darby Canine Kidney Cells
RNA-Binding Proteins / chemistry*
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism*
Up-Regulation*

Substances

A1CF protein, human
IL6 protein, human
Interleukin-6
RNA-Binding Proteins