title: microRNA-124 is down regulated in nerve-injured motor neurons and it potentially targets mRNAs for KLF6 and STAT3.
abstract: MicroRNA (miRNA) is a small non-coding RNA that regulates gene expression by degrading target mRNAs or inhibiting translation. Although many miRNAs play important roles in various conditions, it is unclear whether miRNAs are involved in motor nerve regeneration. In this study, we identified the possible implication of miR-124 in nerve regeneration using a mouse hypoglossal nerve injury model. The significant down-regulation of miR-124 was observed in injured hypoglossal motor neurons after nerve injury, and this transient down-regulation showed a clear inverse correlation with the up-regulation of KLF6 and STAT3, known as axon elongation factor and regeneration-associated molecules, respectively. Furthermore, the luciferase assay and in vitro gain of function methods supported that both genes could be potent targets of miR-124. These results suggest that injury-induced repression of miR-124 may be implicated in the regulation of expression of several injury-associated transcription factors, which are crucial for appropriate nerve regeneration.
authors.affiliation: Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nagata
authors.affiliation: Department of Anatomy and Neurobiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Hama
authors.affiliation: Department of Anatomy and Neurobiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan; Department of Functional Anatomy & Neuroscience, Graduate School of Medicine, 65 Tsurumaicho, Showa-ku, Nagoya 466-8550, Japan; CREST, JST, Nagoya University, Graduate School of Medicine, 65 Tsurumaicho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kiryu-Seo
authors.affiliation: Department of Anatomy and Neurobiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan; Department of Functional Anatomy & Neuroscience, Graduate School of Medicine, 65 Tsurumaicho, Showa-ku, Nagoya 466-8550, Japan; CREST, JST, Nagoya University, Graduate School of Medicine, 65 Tsurumaicho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: kiyama@med.nagoya-u.ac.jp.
authors.forename: H
authors.initials: H
authors.lastname: Kiyama
mesh_terms: D000818:Animals; D019771:Axotomy; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D061228:Hypoglossal Nerve Injuries / Q000473:pathology*; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: C491358:Klf6 protein, mouse; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse
keywords: 3′-UTR; 3′-untranslated region; CT; IL6 receptor; IL6R; ISH; KLF6; Krüppel-like factor 6; STAT3; cycle threshold; expression regulation; hypoglossal nerve; in situ hybridization histochemistry; miRNA; microRNA; nerve injury; neuronal regeneration; signal transducer and activator of transcription 3; transcription factor