title: Identification of ULK1 as a novel biomarker involved in miR-4487 and miR-595 regulation in neuroblastoma SH-SY5Y cell autophagy.
abstract: 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 ~ 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.
authors.affiliation: Department of Gastrointestinal Surgery, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 1] Department of Gastrointestinal Surgery, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [2] Northwestern University, Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, Illinois 60611, USA.
authors.forename: Shuya
authors.initials: S
authors.lastname: Wang
authors.affiliation: 1] Department of Gastrointestinal Surgery, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [2] School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xie
authors.affiliation: Department of Gastrointestinal Surgery, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Sicheng
authors.initials: S
authors.lastname: Song
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.affiliation: 1] Department of Gastrointestinal Surgery, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [2] Collaborative Innovation Center for Biotherapy, Department of Pharmacology &Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ouyang
authors.affiliation: Department of Gastrointestinal Surgery, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
mesh_terms: D001343:Autophagy / Q000235:genetics; D000071189:Autophagy-Related Protein-1 Homolog; D015415:Biomarkers; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D034622:RNA Interference; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D047908:Intracellular Signaling Peptides and Proteins; C000609694:MIRN4487 microRNA, human; D035683:MicroRNAs; C000609695:microRNA595 microRNA, human; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C484754:ULK1 protein, human