title: Role of Beclin-1-Mediated Autophagy in the Survival of Pediatric Leukemia Cells.
abstract: OBJECTIVE
  Acute and chronic leukemia are severe malignant cancers worldwide, and can occur in pediatric patients. Since bone marrow cell transplantation is seriously limited by the availability of the immune-paired donor sources, the therapy for pediatric leukemia (PL) remains challenging. Autophagy is essential for the regulation of cell survival in the harsh environment. However, the role of autophagy in the survival of PL cells under the oxidative stress, e.g. chemotherapy, remain ill-defined. In the current study, we addressed these questions.
  
  
  METHODS
  We analyzed the effects of oxidative stress on the cell viability of PL cells in vitro, using a CCK-8 assay. We analyzed the effects of oxidative stress on the apoptosis and autophagy of PL cells. We analyzed the levels of Beclin-1 and microRNA-93 (miR-93) in PL cells. Prediction of binding between miR-93 and 3'-UTR of Beclin-1 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. The relationship between levels of miR-93 and patients' survival was analyzed in PL patients.
  
  
  RESULTS
  We found that oxidative stress dose-dependently increased autophagy in PL cells. While low-level oxidative stress did not increase apoptosis, high-level oxidative stress increased apoptosis, seemingly from failure of autophagy-mediated cell survival. High-level oxidative stress appeared to suppress the protein levels of an autophagy protein Beclin-1 in PL cells, possibly through induction of miR-93, which inhibited the translation of Beclin-1 mRNA via 3'-UTR binding.
  
  
  CONCLUSIONS
  Beclin-1-mediated autophagy plays a key role in the survival of PL cells against oxidative stress. Induction of miR-93 may increase the sensitivity of PL cells to oxidative stress during chemotherapy to improve therapeutic outcome.
authors.affiliation: Department of Pediatrics Hematology-Oncology, the Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wu
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Feng
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhao
authors.forename: Futian
authors.initials: F
authors.lastname: Ma
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.forename: Hongming
authors.initials: H
authors.lastname: Guo
authors.forename: Chaonan
authors.initials: C
authors.lastname: Li
authors.forename: Huan
authors.initials: H
authors.lastname: Du
authors.forename: Baoxi
authors.initials: B
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D001483:Base Sequence; D000071186:Beclin-1 / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D014176:Protein Biosynthesis; D015398:Signal Transduction; D016019:Survival Analysis
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; C491997:BECN1 protein, human; D000071186:Beclin-1; C543350:MIRN93 microRNA, human; D035683:MicroRNAs; D006861:Hydrogen Peroxide; D008156:Luciferases