MiR-21 is an Ngf-modulated microRNA that supports Ngf signaling and regulates neuronal degeneration in PC12 cells.
The neurotrophins Ngf, Bdnf, NT-3, NT4-5 have key roles in development, survival, and plasticity of neuronal cells. Their action involves broad gene expression changes at the level of transcription and translation. MicroRNAs (miRs)-small RNA molecules that control gene expression post-transcriptionally-are increasingly implicated in regulating development and plasticity of neural cells. Using PC12 cells as a model system, we show that Ngf modulates changes in expression of a variety of microRNAs, including miRs known to be modulated by neurotrophins-such as the miR-212/132 cluster-and several others, such as miR-21, miR-29c, miR-30c, miR-93, miR-103, miR-207, miR-691, and miR-709. Pathway analysis indicates that Ngf-modulated miRs may regulate many protein components of signaling pathways involved in neuronal development and disease. In particular, we show that miR-21 enhances neurotrophin signaling and controls neuronal differentiation induced by Ngf. Notably, in a situation mimicking neurodegeneration-differentiated neurons deprived of Ngf-this microRNA is able to preserve the neurite network and to support viability of the neurons. These findings uncover a broad role of microRNAs in regulating neurotrophin signaling and suggest that aberrant expression of one or more Ngf-modulated miRs may be involved in neurodegenerative diseases.
Istituto di Biologia e Patologia Molecolari (IBPM) CNR, Dipartimento di Biologia e Biotecnologie Università Sapienza, 00185, Rome, Italy, enrica.montalban@gmail.com.
Enrica
E
Montalban
Nicola
N
Mattugini
Roberta
R
Ciarapica
Claudia
C
Provenzano
Mauro
M
Savino
Fiorella
F
Scagnoli
Gianluca
G
Prosperini
Claudia
C
Carissimi
Valerio
V
Fulci
Carmela
C
Matrone
Pietro
P
Calissano
Sergio
S
Nasi
D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020932:Nerve Growth Factor / Q000502:physiology*; D016501:Neurites / Q000648:ultrastructure; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D016716:PC12 Cells; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D017362:Cyclic AMP Response Element-Binding Protein; D035683:MicroRNAs; D012334:RNA, Neoplasm; C546082:mirn21 microRNA, rat; D020932:Nerve Growth Factor