title: Long non-coding RNA Malat1 promotes neurite outgrowth through activation of ERK/MAPK signalling pathway in N2a cells.
abstract: Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are playing critical roles in neurogenesis, yet the underlying molecular mechanisms remain largely elusive. Neurite outgrowth is an early step in neuronal differentiation and regeneration. Using in vitro differentiation of neuroblastoma-derived Neuro-2a (N2a) cell as a model, we performed expression profiling to identify lncRNAs putatively relevant for neurite outgrowth. We identified that Metastasis-associated lung adenocarcinoma transcript 1 (Malat1) was one of the most significantly up-regulated lncRNAs during N2a cell differentiation. Malat1 knockdown resulted in defects in neurite outgrowth as well as enhanced cell death. To pinpoint signalling pathways perturbed by Malat1 depletion, we then performed a reporter-based screening to examine the activities of 50 signalling pathways in Malat1 knockdown cells. We found that Malat1 knockdown resulted in conspicuous inhibition of Mitogen-Activated Protein Kinase (MAPK) signaling pathway as well as abnormal activation of Peroxisome proliferator-activated receptor (PPAR) and P53 signalling pathway. Inhibition of ERK/MAPK pathway with PD98059 potently blocked N2a cell neurite outgrowth, whereas phorbol 12-myristate 13-acetate-induced ERK activation rescued defects in neurite outgrowth and cell death induced by Malat1 depletion. Together, our results established a critical role of Malat1 in the early step of neuronal differentiation through activating ERK/MAPK signalling pathway.
authors.affiliation: Department of Neurology, West China Hospital of Sichuan University, Chengdu, China. leilei_25@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
authors.forename: Peimin
authors.initials: P
authors.lastname: Feng
authors.affiliation: Department of Neurology, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Neurology, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Shixu
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Neurology, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Jialan
authors.initials: J
authors.lastname: Duan
authors.affiliation: Department of Neurology, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhou
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D017124:Conserved Sequence / Q000235:genetics; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020935:MAP Kinase Signaling System / Q000235:genetics*; D051379:Mice; D016501:Neurites / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*
chemical_list: C557040:Malat1 long non-coding RNA, mouse; D062085:RNA, Long Noncoding; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: 
  ERK
  ; LncRNA; Malat1; neurite outgrowth