Identification of ULK1 as a novel biomarker involved in miR-4487 and miR-595 regulation in neuroblastoma SH-SY5Y cell autophagy

被引:28
作者
Chen, Yi [1 ]
Wang, Shuya [1 ]
Zhang, Lan [1 ,2 ]
Xie, Tao [1 ]
Song, Sicheng [1 ]
Huang, Jian [2 ]
Zhang, Yonghui [1 ,3 ]
Ouyang, Liang [1 ]
Liu, Bo [1 ]
机构
[1] Sichuan Univ, West China Hosp, Collaborat Innovat Ctr Biotherapy, Dept Gastrointestinal Surg,State Key Lab Biotherap, Chengdu 610041, Peoples R China
[2] Shenyang Pharmaceut Univ, Sch Tradit Chinese Mat Med, Shenyang 110016, Peoples R China
[3] Tsinghua Univ, Sch Med, Dept Pharmacol & Pharmaceut Sci, Collaborat Innovat Ctr Biotherapy, Beijing 100084, Peoples R China
基金
中国国家自然科学基金;
关键词
MICRORNAS; TARGET; PREDICTION; EEF2K;
D O I
10.1038/srep11035
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Autophagy, referring to an evolutionarily conserved, multi-step lysosomal degradation process, has been well-known to be initiated by Unc-51 like kinase 1 (ULK1) with some links to Parkinson's disease (PD). MicroRNAs (miRNAs), small and non-coding endogenous RNAs 22 similar to 24 nucleotides (nt) in length, have been demonstrated to play an essential role for modulating autophagy. Recently, the relationships between miRNAs and autophagy have been widely reported in PD; however, how microRNAs regulate autophagy still remains in its infancy. Thus, in this study, we computationally constructed the ULK1-regulated autophagic kinase subnetwork in PD and further identified ULK1 able to negatively regulate p70(S6K) in starvation-induced autophagy of neuroblastoma SH-SY5Y cells. Combination of in silico prediction and microarray analyses, we identified that miR-4487 and miR-595 could target ULK1 and experimentally verified they could negatively or positively regulate ULK1-mediated autophagy. In conclusion, these results may uncover the novel ULK1-p70(S6K) autophagic pathway, as well as miR-4487 and miR-595 as new ULK1 target miRNAs. Thus, these findings would provide a clue to explore ULK1 and its target miRNAs as potential biomarkers in the future PD therapy.
引用
收藏
页数:10
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