Mir-206 partially rescues myogenesis deficiency by inhibiting CUGBP1 accumulation in the cell models of myotonic dystrophy.
Neurol Res
; 41(1): 9-18, 2019 Jan.
Article
in En
| MEDLINE
| ID: mdl-30281408
ABSTRACT
Objectives:
In this study, we aim to determine how CUG-expansion and the abundance of Celf1 regulates normal myocyte differentiation and reveal the role ofmiR-206 in myotonic dystrohy and explore a possible gene therapy vector.Methods:
we set up CUG-expansion and Celf1 overexpression C2C12 cell models to imitate the myocyte differentiation defects of DM1, then transfected AdvmiR-206 into cell models, tested the level of myogenic markers MyoD, MyoG, Mef2c, Celf1 by RT-PCRand Western Blotting, detected myotube formation by myosin heavy chain immunostaining.Result:
3'-UTR CUG-expansion leads to myotube defects and impaired myoblasts differentiation. Overexpression of Celf1 inhibits myoblast differentiation and impairs differentiation. Knockdown of Celf1 partially rescues differentiation defects of myoblasts harboring CUG-expansion. miR-206 incompletely reverses myoblast differentiation inhibition induced by CUG-expansion and partially recuses myoblast differentiation defects induced by Celf1 overexpression.Conclusions:
Ectopic miR-206 mimicking the endogenous temporal patterns specifically drives a myocyte program that boosts myoblast lineages, likely by promoting the expression of MyoD to rectify the myogenic deficiency by stimulating the accumulation of Celf1. Abbreviations DMPK (dystrophia myotonica protein kinase); 3'-UTR (3'-untranslated region); MBNL1 (muscleblind-like [Drosophila]); DM1 (myotonic dystrophy type 1); GFP (green fluorescent protein); RT-PCR (quantitative reverse transcriptase-polymerase chain reaction); shRNA (short hairpin RNA).Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Muscle Development
/
Myoblasts
/
MicroRNAs
/
CELF1 Protein
/
Myotonic Dystrophy
Limits:
Animals
Language:
En
Journal:
Neurol Res
Year:
2019
Document type:
Article
Affiliation country:
China
Country of publication:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM