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2017 ; 8
(10
): e3153
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Circular RNA profiling reveals an abundant circLMO7 that regulates myoblasts
differentiation and survival by sponging miR-378a-3p
#MMPMID29072698
Wei X
; Li H
; Yang J
; Hao D
; Dong D
; Huang Y
; Lan X
; Plath M
; Lei C
; Lin F
; Bai Y
; Chen H
Cell Death Dis
2017[Oct]; 8
(10
): e3153
PMID29072698
show ga
Circular RNAs (circRNAs) have been identified from various tissues and species,
but their regulatory functions during developmental processes are not well
understood. We examined circRNA expression profiles of two developmental stages
of bovine skeletal muscle (embryonic and adult musculus longissimus) to provide
first insights into their potential involvement in bovine myogenesis. We
identified 12?981 circRNAs and annotated them to the Bos taurus reference genome,
including 530 circular intronic RNAs (ciRNAs). One parental gene could generate
multiple circRNA isoforms, with only one or two isoforms being expressed at
higher expression levels. Also, several host genes produced different isoforms
when comparing development stages. Most circRNA candidates contained two to seven
exons, and genomic distances to back-splicing sites were usually less than 50?kb.
The length of upstream or downstream flanking introns was usually less than
105?nt (mean?11?000?nt). Several circRNAs differed in abundance between
developmental stages, and real-time quantitative PCR (qPCR) analysis largely
confirmed differential expression of the 17 circRNAs included in this analysis.
The second part of our study characterized the role of circLMO7-one of the most
down-regulated circRNAs when comparing adult to embryonic muscle tissue-in bovine
muscle development. Overexpression of circLMO7 inhibited the differentiation of
primary bovine myoblasts, and it appears to function as a competing endogenous
RNA for miR-378a-3p, whose involvement in bovine muscle development has been
characterized beforehand. Congruent with our interpretation, circLMO7 increased
the number of myoblasts in the S-phase of the cell cycle and decreased the
proportion of cells in the G0/G1 phase. Moreover, it promoted the proliferation
of myoblasts and protected them from apoptosis. Our study provides novel insights
into the regulatory mechanisms underlying skeletal muscle development and
identifies a number of circRNAs whose regulatory potential will need to be
explored in the future.