Expression patterns of regulatory lncRNAs and miRNAs in muscular atrophy models induced by starvation in vitro and in vivo

Abstract

Starvation or severe deprivation of nutrients, which is commonly seen in surgical patients, can result in catabolic changes in skeletal muscles, such as muscle atrophy. Therefore, it is important to elucidate the underlying molecular regulatory mechanisms during skeletal muscle atrophy. In the present study, muscular atrophy was induced by starvation and the results demonstrated that myosin heavy chain was decreased, whereas muscle RING finger protein 1 and atrogin-1 were increased, both in vitro and in vivo. The impact of starvation on the expression patterns of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) was next determined. The expression patterns of miR-23a, miR-206 and miR-27b in the starved mice exhibited similar trends as those in starved C2C12 cells in vitro, whereas the expression patterns of six other miRNAs (miR-18a, miR-133a, miR-133b, miR-186, miR-1a and miR-29b) differed between the in vivo and the in vitro starvation models. The present study indicated that in vitro expression of the selected miRNAs was not completely consistent with that in vivo. By contrast, lncRNAs showed excellent consistency in their expression patterns in both the in vitro and in vivo starvation models; six of the lncRNAs (Atrolnc-1, long intergenic non-protein coding RNA of muscle differentiation 1, Myolinc, lncRNA myogenic differentiation 1, Dum and muscle anabolic regulator 1) were significantly elevated in starved tissues and cells, while lnc-mg was significantly decreased, compared with the control groups. Thus, lncRNAs involved in muscle atrophy have the potential to be developed as diagnostic tools.

Role of miRNAs and lncRNAs in dexamethasone‑induced myotube atrophy in vitro

“…The current study indicated that the expression of miR-133a, miR-133b and miR-206 were upregulated in the DEX group. These results were consistent with previous studies that demonstrated increased expression of miR-133a and miR-206 in animal models of muscular dystrophy and in the serum of effected patients ( 30 , 48 , 53 ). Myogenic regulatory factors include MyoD, MyoG, Myf5 and MRF4, which servean important role in the regulation of myogenic differentiation after proliferation of minisatellite cells ( 54 ).…”

“…RT-qPCR was used to determine the expression of multiple miRNAs that have previously been revealed to be associated with muscle development in DEX-treated and control C2C12 cells. miRNAs that were previously reported in the literature were identified and nine miRNAs [miR-133a ( 19 ), miR-133b ( 18 , 44 ), miR-206( 45 ), miR-18a ( 46 ), miR-186( 47 ), miR-1a-3p ( 21 , 48 ), miR-23a-3p ( 27 , 49 ), miR-27b ( 50 ), miR-29b-3p ( 16 )] were selected for examination in the present study, which exhibited expression similar to that previously reported. The results indicated that the expression of miR-133a, miR-133b and miR-206 was significantly increased in the DEX-treated group compared with the control group ( Fig.…”

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

“…LncRNA expression is deregulated during states of metabolic stress such as in diabetes and altered expression patterns can be associated with development of diabetic cardiomyopathy [137]. Conversely, nutrient deprivation can acutely change expression levels of lncRNAs in skeletal muscle [138]. There are dynamic expression levels of lncRNAs in the heart, changing during the first week of life, suggesting an important role for lncRNAs in postnatal cardiomyocyte maturation [139].…”

Regulation of Skeletal Muscle Atrophy in Cachexia by MicroRNAs and Long Non-coding RNAs

“…TRAF6 is also directly targeted by miR-125b-5p. The expression of miR-125b-5p is downregulated in both atrophic fasting C2C12 myotubes and denervated TA muscles (Qiu et al, 2019), and our research showed that several miRNAs were downregulated under atrophic fasting/starvation conditions in C2C12 myotubes or mice (Lei et al, 2019). Overexpression of miR-125b-5p protects skeletal muscle samples by targeting TRAF6 via downregulation of Atrogin-1, MuRF-1, and autophagy-lysosome system-related proteins (Qiu et al, 2019).…”