Non-Coding RNAs in the Transcriptional Network That Differentiates Skeletal Muscles of Sedentary from Long-Term Endurance- and Resistance-Trained Elderly
Abstract
:1. Introduction
2. Results
2.1. Micro RNA
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- miR-181a-2-3p (upregulated in TRA versus SED), already mentioned above, has an anti-inflammatory role [37].
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- miR-199a-5p (downregulated in TRA versus SED) is modulated in the diabetic muscle, where its role in targeting Slc2a4/GLUT4 and Hk2/HK2 expression was confirmed [38], it is involved in myogenesis and dysregulated in Duchenne Muscular Dystrophy (DMD) [39], its upregulation, along with that of miR-497-5p and of other four miRNAs is associated with mitochondrial dysfunction in DMD [40].
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- miR-193a-3p (downregulated in TRA versus SED) was found to be deregulated in Myotonic Dystrophy Type-2 [41].
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- miR-20a-5p (upregulated in TRA versus SED) is involved in myoblast proliferation and differentiation [42].
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- miR-486-5p (upregulated in TRA versus SED), the only myomiR differentially expressed in TRA versus SED VL samples, is rightly considered a myogenesis regulator, since it is implicated in the inhibition of myocardin-related transcription factor A (MRTF-A), which modulates one of the last steps of myogenic differentiation [43]; interestingly, it can be upregulated by administration of green tea polyphenol epigallocatechin-3-gallate, with benefits for the ageing skeletal muscle [44]; moreover, its involvement in a complex metabolic regulation of muscle hypertrophy during aerobic exercise was reported [45].
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- miR-100-5p (downregulated in TRA versus SED) is involved in the same complex metabolic regulation following aerobic exercise that has been reported for miR-486-5p [45].
2.2. Long Non-Coding RNA
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- Small Nucleolar RNA Host Gene G7 (SNHG7). Upon observing a positive correlation between SNHG7 and GALNT7 and a negative correlation between SNHG7 and miR-34a in colorectal cancer lines. it was suggested that SNHG7 upregulates GALNT7 expression by sponging miR-34a [50]. Another paper reported that SNHG7 antagonizes miR-193b to increase the expression of FAIM2 [51]. By evaluating our data sets, we confirmed the positive correlation between SNHG7 and both GALNT7 and FAIM2. since the three appear to be significantly downregulated in TRA in comparison with SED samples, on the other hand, neither miR-34a or miR-193b were differentially expressed. While the effect of GALNT7 and FAIM2 in tumor progression is known (the former favoring and the latter impairing tumor growth), their function in the context of skeletal muscle, exercise and contrast to sarcopenia is less obvious. GALNT7 is involved in several transcriptional networks, including the one involving the competing endogenous RNA TP73-AS1—which sequesters miR-103a, and RP11-798M19.6. There is evidence that FAIM2 expression may increase susceptibility to type 2 diabetes associated with obesity [52] and to obstructive sleep apnea-related cardiac injury [53], thus, the FAIM2 downregulation (found in TRA subjects) appears to bear favorable effects.
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- Growth Arrest Specific 5 (non-protein coding) (GAS5) is a small nucleolar RNA host gene, acting as a tumor suppressor, probably by favoring apoptosis [54]. It has multiple interactions with miRNAs [48] and interacts with mTOR in a complex reciprocal inhibitory relationship [55]. Interestingly, part of the secondary RNA structure of the encoded transcript mimics the glucocorticoid response element, thus interfering with its binding with the glucocorticoid receptor, as well as with the binding of androgen, progesterone and mineralocorticoid receptors to their response elements [48,56]. GAS5 is downregulated in TRA VL, thus favoring the activation of the above mentioned receptors, with particular emphasis on the anti-inflammatory role of glucocorticoid receptor transactivation and the role of androgens in increasing muscle mass and strength. GAS5 interacts with multiple mRNAs and miRNAs, in particular it is targeted by miR-20a-5p and miR-106, both upregulated in TRA VL. Moreover, it was shown that GAS5 knockdown upregulates VEGFA [57], an angiogenetic growth factor which is overexpressed in TRA skeletal muscles.
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- Small Nucleolar RNA host gene 12 (SNHG12) acts as an oncogene, by sponging miR-181a [58]. Soriano-Arroquia et al. [59] identified miR-181a as a positive regulator of the sirtuin1 (SIRT1) gene expression in skeletal muscle and the miR-181a:SIRT1 interactions as regulators of myotube size. They also reported that the expression of miR-181a and of SIRT1 was decreased in skeletal muscle from old mice. In another paper published in 2020, miR-181a was identified as putative regulator of mitochondrial dynamics [60]. Therefore, the fact that we report here a downregulation of SNHG12 coupled with an upregulation of its target miR-181a in TRA VL constitutes a further advancement in the understanding of the mechanisms underlying the preservation of the mitochondrial function and of skeletal muscle morphology and performance induced by long-term high-level training in elders [7].
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- HOXA Transcript Antisense RNA, Myeloid-specific 1 (HOTAIRM1) is one of the best studied lncRNA, because of its possible oncogenic role [61]. In TRA VL HOTAIRM1 is downregulated and one of its targets, miR-20a-5p is upregulated. It is difficult to realize the role of the pair HOTAIM1-miR-20a-5p in the specific context of skeletal muscle, exercise training and contrast to sarcopenia since there are 190 genes that are both validated targets of miR-20a-5p and significantly downregulated in TRA VL. The specific functions of these 190 gene products range from being part of signaling pathways, regulating cell cycle and apoptosis, controlling transcription and translation, including the synthesis of a number of ribosomal proteins, as pointed out above.
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- Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is one of the best studied lncRNA. It promotes epithelial-mesenchymal transition by activating both the TGF-beta and the WNT pathways, as well as angiogenesis. Reciprocal repression between MALAT1 and miR-140 was demonstrated in human gliomas [62]. Liu et al. [63] reported that exercise downregulated MALAT1 expression in the insulin-resistant mouse model, resulting in reduced resistin levels. Neither study apparently applies to our experimental setting, since MALAT1 was upregulated in TRA versus SED VL, but miR-140 was not differentially expressed; therefore, the effect of exercise training in MALAT1 regulation is apparently different in subjects that are not insulin resistant.
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- Other differentially expressed lncRNAs are involved in tumorigenesis. Summarizing, SNHG7, SNHG12, HOTAIRM1, SNHG14, HOXD-AS1, SNHG15, SNHG1, LINC00152, HOXC-AS1,MALAT1 have all been described to promote cell proliferation, invasion and migration, though by different mechanisms. Apart from SNHG14 and MALAT1, they were all downregulated in TRA VL. On the other hand, GAS5 and TP73-AS1 have tumor suppressor activities, the former being down- and the latter up-regulated in TRA VL. The relationships of these lncRNAs with the experimental model, presented here, is difficult to interpret.
3. Discussion
4. Materials and Methods
4.1. Subjects, Biopsies and RNA Extraction
4.2. RNA Analysis
4.2.1. Heatmaps and Principal Component Analysis
4.2.2. Micro- and Long Non Coding-RNA Targets
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
SED | sedentary |
TRA | trained |
ET | endurance training |
RT | resistance training |
KEGG | Kyoto Encyclopedia of Genes and Genomes |
NGS | Next Generation Sequencing |
miRNA | microRNA |
lncRNA | long non-coding RNA |
cpm | counts per million |
References
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miRNA | Up- or Down-Regulated in TRA versus SED VL | logFC | p Value | Adj. p. Value | No. of Validated Targets | No. of Validated Targets That Are Differentially Expressed [7] and with a Trend Opposite to the Trensd of miRNAs |
---|---|---|---|---|---|---|
hsa-miR-7847-3p | Up | 4.44 | 1.52 × 10−8 | 1.00 × 10−4 | 200 | 38 |
hsa-let-7c-5p | Down | −0.99 | 9.24 × 10−8 | 3.05 × 10−4 | 484 | 147 |
hsa-miR-4298 | Up | 5.02 | 1.45 × 10−7 | 3.18 × 10−4 | 46 | 7 |
hsa-miR-6812-5p | Up | 2.46 | 5.92 × 10−7 | 9.77 × 10−4 | 65 | 17 |
hsa-mir-3175 | Down | −3.51 | 2.12 × 10−6 | 1.75 × 10−3 | 205 | 53 |
hsa-miR-3197 | Down | −3.10 | 1.98 × 10−6 | 1.75 × 10−3 | 23 | 4 |
hsa-miR-3911 | Up | 4.06 | 1.96 × 10−6 | 1.75 × 10−3 | 70 | 13 |
hsa-miR-6510-5p | Down | −1.47 | 5.31 × 10−6 | 2.69 × 10−3 | 85 | 21 |
hsa-miR-4521 | Up | 3.69 | 6.49 × 10−6 | 3.06 × 10−3 | 26 | 3 |
hsa-miR-574-5p | Down | −2.18 | 1.72 × 10−5 | 5.96 × 10−3 | 348 | 89 |
hsa-miR-181a-2-3p | Up | 1.90 | 2.39 × 10−5 | 7.00 × 10−3 | 70 | 10 |
hsa-miR-664b-3p | Down | −0.86 | 2.94 × 10−5 | 7.46 × 10−3 | 145 | 43 |
hsa-miR-199a-5p | Down | −1.71 | 3.65 × 10−5 | 8.60 × 10−3 | 139 | 36 |
hsa-miR-193a-3p | Down | −2.56 | 3.65 × 10−5 | 8.60 × 10−3 | 115 | 41 |
hsa-miR-4669 | Up | 2.52 | 4.65 × 10−5 | 9.90 × 10−3 | 29 | 10 |
hsa-miR-4269 | Down | −1.80 | 5.38 × 10−5 | 1.00 × 10−2 | 114 | 30 |
hsa-miR-497-5p | Down | −1.60 | 1.62 × 10−4 | 2.00 × 10−2 | 426 | 135 |
hsa-miR-4485-3p | Up | 2.00 | 1.60 × 10−4 | 2.55 × 10−2 | 6 | 1 |
hsa-miR-7110-5p | Down | −3.47 | 1.66 × 10−4 | 2.55 × 10−2 | 87 | 20 |
hsa-miR-5100 | Down | −1.43 | 2.01 × 10−4 | 2.82 × 10−2 | 57 | 19 |
hsa-miR-486-3p | Up | 1.72 | 2.17 × 10−4 | 2.98 × 10−2 | 133 | 21 |
hsa-miR-7150 | Down | −2.68 | 2.31 × 10−4 | 3.11 × 10−2 | 102 | 28 |
hsa-miR-20a-5p | Up | 1.12 | 2.51 × 10−4 | 3.19 × 10−2 | 1044 | 172 |
hsa-miR-4429 | Down | −1.80 | 2.77 × 10−4 | 3.33 × 10−2 | 68 | 20 |
hsa-miR-4484 | Down | −2.13 | 3.06 × 10−4 | 3.54 × 10−2 | 53 | 16 |
hsa-miR-320d | Down | −1.54 | 3.13 × 10−4 | 3.57 × 10−2 | 70 | 21 |
hsa-miR-486-5p | Up | 1.04 | 3.20 × 10−4 | 3.58 × 10−2 | 54 | 11 |
hsa-miR-6778-5p | Up | 1.82 | 4.14 × 10−4 | 4.18 × 10−2 | 128 | 30 |
hsa-miR-100-5p | Down | −0.90 | 4.73 × 10−4 | 4.61 × 10−2 | 247 | 80 |
hsa-miR-4443 | Down | −1.24 | 4.75 × 10−4 | 4.61 × 10−2 | 80 | 13 |
hsa-miR-106a-5p | Up | 0.85 | 4.99 × 10−4 | 4.77 × 10−2 | 673 | 118 |
hsa-miR-3651 | Down | −1.80 | 5.24 × 10−4 | 4.87 × 10−2 | 30 | 13 |
KEGG Name | Overlap | p Value | Adjusted p Value | Differentially Expressed miRNA Target Genes | Number of Target Genes Modulated by miRNAs versus Total Differentially Expressed Genes [7] in the Pathway |
---|---|---|---|---|---|
Cell cycle | 27/124 | 5.63 × 10−8 | 1.74 × 10−5 | RB1;YWHAE;GSK3B;CDKN1A;CUL1;ORC4;CCNB1;CCND2;CCND1;RAD21;ORC2;E2F1;EP300;E2F3;YWHAH;CREBBP;SMAD4;SMAD3;SMC1A;YWHAZ;STAG2;RBL1;TFDP2;ATM;TP53;MAD1L1;ANAPC1 | 27/54 (50%) |
AMPK signaling pathway | 21/120 | 4.05 × 10−4 | 4.16 × 10−5 | RAB2A;CPT1A;PRKAA2;STRADB;PPP2R2A;IGF1;PPP2R5C;ADIPOR2;MTOR;CAMKK2;RPTOR;RAB10;CCND1;RPS6KB1;PPP2R5E;SCD;EIF4EBP1;ULK1;PPARG;MAP3K7;PFKP | 21/66 (31%) |
TGF-beta signaling pathway | 16/90 | 7.74 × 10−6 | 1.59 × 10−4 | CREBBP;SMAD4;SMAD3;CUL1;BMP8B;ACVR1B;SMAD6;RHOA;RGMA;TGFBR2;BMP2;RBL1;RPS6KB1;ID4;EP300;BMPR1A | 16/43 (37%) |
Thyroid hormone signaling pathway | 19/116 | 3.98 × 10−6 | 1.36 × 10−4 | GSK3B;MAP2K1;CREBBP;THRA;NCOA3;ATP2A2;ATP1B3;SLC16A10;ATP1A2;MTOR;MED12;CCND1;TBC1D4;PLCG2;PLCE1;EP300;RAF1;TP53;PFKP | 19/64 (29%) |
p53 signaling pathway | 13/72 | 4.58 × 10−5 | 5.23 × 10−4 | CDKN1A;PTEN;IGF1;CCNB1;CCND2;CCND1;SESN3;CCNG1;BCL2;FAS;ATM;MDM4;TP53 | 13/38 (29%) |
Focal adhesion | 27/199 | 1.91 × 10−6 | 9.79 × 10−5 | GSK3B;FLT1;ROCK2;PTEN;THBS2;ARHGAP35;MYLK3;CRKL;PPP1CB;MAPK8;CCND2;CCND1;FLNA;PAK2;PDGFRA;MAP2K1;PPP1R12A;CAV1;ITGA1;IGF1;RHOA;VEGFA;RAPGEF1;BCL2;GRB2;RAF1;VCL | 27/105 (25%) |
FoxO signaling pathway | 20/132 | 7.60 × 10−6 | 1.67 × 10−4 | GABARAPL1;MAP2K1;CREBBP;SMAD4;CDKN1A;SMAD3;PRKAA2;PTEN;IGF1;MAPK14;SOD2;TGFBR2;CCNB1;MAPK8;CCND2;CCND1;EP300;GRB2;ATM;RAF1 | 20/63 (31%) |
Cellular senescence | 23/160 | 4.05 × 10−6 | 1.25 × 10−4 | RB1;MAP2K1;CDKN1A;SMAD3;TRAF3IP2;PTEN;MAPK14;MTOR;TGFBR2;PPP1CB;CCNB1;CCND2;RBL1;CCND1;RBBP4;EIF4EBP1;E2F1;ATM;E2F3;BTRC;RAF1;TP53;PPID | 23/81 (28%) |
Hippo signaling pathway | 23/160 | 4.05 × 10−6 | 1.14 × 10−4 | YWHAE;GSK3B;TCF7L2;SMAD4;SMAD3;FZD5;FZD9;BMP8B;PPP2R2A;LIMD1;YWHAZ;AMOT;TGFBR2;PPP1CB;BMP2;CCND2;LATS2;CCND1;DVL3;BTRC;TEAD1;BMPR1A;YWHAH | 23/71 (32%) |
Mitophagy | 12/65 | 7.12 × 10−5 | 7.31 × 10−4 | BECN1;BCL2L13;GABARAPL1;USP15;MAPK8;CSNK2A1;UBB;ATG9A;E2F1;MITF;ULK1;TP53 | 12/33 (36%) |
mTOR signaling pathway | 22/152 | 5.83 × 10−6 | 1.38 × 10−4 | GSK3B;MAP2K1;PRKAA2;FZD5;STRADB;FZD9;PTEN;IGF1;RHOA;MTOR;RPTOR;FLCN;SLC7A5;CLIP1;RPS6KB1;EIF4EBP1;DVL3;ULK1;GRB2;RICTOR;RAF1;ATP6V1F | 22/72 (30%) |
Autophagy | 19/128 | 1.72 × 10−5 | 2.79 × 10−4 | BECN1;GABARAPL1;MAP2K1;MTMR3;PRKAA2;ATG9A;PTEN;MTOR;CAMKK2;ERN1;RPTOR;MAPK8;RPS6KB1;LAMP2;ATG2A;BCL2;ULK1;RAF1;MAP3K7 | 19/66 (28%) |
Adherens junction | 12/72 | 1.98 × 10−4 | 1.56 × 10−3 | TCF7L2;CREBBP;SMAD4;SMAD3;CSNK2A1;EP300;WASL;MAP3K7;PTPRF;RHOA;VCL;TGFBR2 | 12/41 (41%) |
Longevity regulating pathway | 15/102 | 1.44 × 10−4 | 1.23 × 10−3 | PRKAA2;CLPB;IGF1;SOD2;ADIPOR2;MTOR;CAMKK2;RPTOR;SESN3;RPS6KB1;EIF4EBP1;ULK1;PPARG;TP53;APPL1 | 15/48 (31%) |
Insulin signaling pathway | 18/137 | 1.44 × 10−4 | 1.20 × 10−3 | GSK3B;PYGB;MAP2K1;PRKAA2;PHKA1;PTPRF;HK2;MTOR;CRKL;PPP1CB;RPTOR;MAPK8;RPS6KB1;PRKAR2A;EIF4EBP1;RAPGEF1;GRB2;RAF1 | 18/80 (22%) |
Wnt signaling pathway | 20/158 | 1.07 × 10−4 | 1.03 × 10−3 | GSK3B;TCF7L2;CREBBP;SMAD4;SMAD3;CSNK2A1;FZD5;ROCK2;CUL1;FZD9;PRICKLE1;RHOA;MAPK8;CCND2;CCND1;EP300;DVL3;BTRC;MAP3K7;TP53 | 20/73 (27%) |
MAPK signaling pathway | 32/295 | 2.71 × 10−5 | 3.63 × 10−4 | FLT1;CSF1;MAX;CRKL;ELK4;CACNG6;FGF7;MAPK8;STMN1;FLNA;MAP2K7;PAK2;MAP3K7;MAP4K3;MAP3K2;PDGFRA;MEF2C;MAP2K1;IGF1;IRAK4;MAPK14;VEGFA;TGFBR2;PPM1A;TAOK1;KIT;NF1;FAS;GRB2;RAF1;TP53;MAP3K12 | 32/134 (23%) |
Neurotrophin signaling pathway | 16/119 | 2.54 × 10−4 | 1.86 × 10−3 | YWHAE;GSK3B;MAP2K1;IRAK4;MAPK14;RHOA;CRKL;MAPK8;PLCG2;BCL2;RAPGEF1;GRB2;RAF1;MAP2K7;TP53;NFKBIB | 16/56 (28%) |
Sphingolipid signaling pathway | 16/119 | 2.54 × 10−4 | 1.82 × 10−3 | MAP2K1;ABCC1;ROCK2;PTEN;PPP2R2A;PPP2R5C;MAPK14;RHOA;GNA13;MAPK8;SPTLC2;PPP2R5E;BCL2;DEGS1;RAF1;TP53 | 16/61 (26%) |
HIF-1 signaling pathway | 14/100 | 3.98 × 10−4 | 2.56 × 10−3 | MAP2K1;CREBBP;CDKN1A;FLT1;CUL2;IGF1;HK2;MTOR;VEGFA;RPS6KB1;EIF4EBP1;PLCG2;BCL2;EP300 | 14/54 (26%) |
mRNA surveillance pathway | 13/91 | 5.21 × 10−4 | 3.15 × 10−3 | HBS1L;SMG1;CPSF7;CPSF2;CSTF2T;PPP2R2A;MSI2;PPP2R5C;MAGOHB;PPP1CB;DDX39B;PPP2R5E;WDR82 | 13/37 (35%) |
Ferroptosis | 7/40 | 3.15 × 10−3 | 1.62 × 10−2 | PRNP;MAP1LC3B;PCBP1;LPCAT3;SLC11A2;ACSL3;TP53 | 7/25 (28%) |
Regulation of actin cytoskeleton | 24/214 | 1.59 × 10−4 | 1.29 × 10−3 | NCKAP1;PDGFRA;MAP2K1;PPP1R12A;ROCK2;RDX;ITGA1;LIMK1;WASL;SSH2;RHOA;ARHGAP35;MYLK3;CRKL;PPP1CB;GNA13;FGF7;PIKFYVE;ARPC3;PIP4K2A;RAF1;PAK2;VCL;PFN2 | 24/110 (24%) |
Ubiquitin mediated proteolysis | 17/137 | 4.33 × 10−4 | 2.72 × 10−3 | UBE2H;FBXW8;CUL5;UBE2B;FBXW7;MGRN1;CUL3;CUL2;CUL1;HUWE1;UBE4B;UBE2S;UBE2Q2;UBE2N;UBA2;BTRC;ANAPC1 | 17/73 (23%) |
Ensembl gene ID | Gene Symbol | log2 FC | p Value | Adj p Value | Validated Targets That Are Differentially Expressed [7] |
---|---|---|---|---|---|
ENSG00000233016 | SNHG7 | −1.42 | 0.000000 | 0.000007 | GALNT7 (−0.91); FAIM2 (−0.72) |
ENSG00000177410 | ZFAS1 | −2.29 | 0.000000 | 0.000009 | KLF2 (−3.06); ZEB1 (0.87); TJP1 (0.61) |
ENSG00000234741 | GAS5 | −1.93 | 0.000000 | 0.000016 | ANXA2 (−2.6); CCND1 (−1.23); E2F1 (−1.12); KLF2 (−3.06); MMP2 (−2.33); PTEN (−0.48); SMAD3 (1.12); TP53 (−1.12); VEGFA (2.60); VIM (−3.32); EIF4E (0.64); IGF1R (0.38); hsa−miR106a−5p (0.85) |
ENSG00000224078 | SNHG14 | 1.97 | 0.000002 | 0.000084 | WASL (0.51) |
ENSG00000224259 | RP11-48O20.4 (LINC01133) | −4.41 | 0.000000 | 0.000016 | KLF2 (−3.06) |
ENSG00000163597 | SNHG16 | 0.71 | 0.000001 | 0.000048 | FBXW7 (1.22) |
ENSG00000224189 | HOXD-AS1 (HAGLR) | −2.25 | 0.000003 | 0.000108 | RUNX3 (−1.64) |
ENSG00000197989 | SNHG12 | −1.51 | 0.000004 | 0.000149 | AMOT (2.00); NOTCH2 (−0.59); hsa−miR−181a (1.90) |
ENSG00000229847 | EMX2OS | −1.46 | 0.000038 | 0.000695 | EMX2 (−1.87) |
ENSG00000233429 | HOTAIRM1 | −1.40 | 0.000018 | 0.000413 | hsa−miR20a−5p (1.12) |
ENSG00000227372 | TP73-AS1 | 0.50 | 0.000284 | 0.003178 | BDH2 (−0.72) |
ENSG00000232956 | SNHG15 | −0.91 | 0.000355 | 0.003793 | KLF2 (−3.06); MMP2 (−2.33); MMP9 (−3.90) |
ENSG00000222041 | LINC00152 (CYTOR) | −1.95 | 0.000577 | 0.005579 | CYTOR (−2.33); BCL2 (0.82); CDKN1A (−2.56); PIK3CB (0.85); VIM (−3.32); FN1 (−1.73) |
ENSG00000255717 | SNHG1 | −0.57 | 0.001889 | 0.014430 | TP53 (−1.12); VIM (−3.32) |
ENSG00000250451 | HOXC-AS1 | −0.86 | 0.002378 | 0.017336 | HOXC6 (−0.55) |
ENSG00000251562 | MALAT1 | 0.67 | 0.006092 | 0.037387 | PCNA (−0.56); CSF1 (−1.94); CA2 (2.39); GPC6 (−2.34); BMPER (−1.10); CA2 (2.39); GPC6 (−2.34); CSF1 (−1.94); LPAR1 (−2.53); COL6A1 (−0.99); MCAM (−1.18); STC1 (−2.51); NNMT (−3.09); CPM (−2.03); CASP9 (0.62); CCL2 (−2.68); CCND1 (−1.23); CDKN1A (−2.56); MMP2 (−2.33); ZEB1 (0.87); SNAI2 (−1.31); MAP2K1 (0.87); MAPK1 (0.67); MAPK14 (0.52); MAPK3 (−1.12); MAPK8 (0.58); MAPK9 (0.96); SFRP1 (−2.97); CLDN5 (−1.99); OCLN (−1.32); CTHRC1 (−2.36); PTBP3 (−0.63); MMP14 (−2.30); PXN (1.26); PIK3CB (0.85); SNCA (−3.25); TP53 (−1.12); ROBO1 (−0.88); PRKCE (0.67); CASP3 (−0.42); CDH5 (0.59); ZEB2 (−0.67); FN1 (−1.73); TJP1 (0.61); RAP1B (−0.58) |
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De Sanctis, P.; Filardo, G.; Abruzzo, P.M.; Astolfi, A.; Bolotta, A.; Indio, V.; Di Martino, A.; Hofer, C.; Kern, H.; Löfler, S.; et al. Non-Coding RNAs in the Transcriptional Network That Differentiates Skeletal Muscles of Sedentary from Long-Term Endurance- and Resistance-Trained Elderly. Int. J. Mol. Sci. 2021, 22, 1539. https://doi.org/10.3390/ijms22041539
De Sanctis P, Filardo G, Abruzzo PM, Astolfi A, Bolotta A, Indio V, Di Martino A, Hofer C, Kern H, Löfler S, et al. Non-Coding RNAs in the Transcriptional Network That Differentiates Skeletal Muscles of Sedentary from Long-Term Endurance- and Resistance-Trained Elderly. International Journal of Molecular Sciences. 2021; 22(4):1539. https://doi.org/10.3390/ijms22041539
Chicago/Turabian StyleDe Sanctis, Paola, Giuseppe Filardo, Provvidenza Maria Abruzzo, Annalisa Astolfi, Alessandra Bolotta, Valentina Indio, Alessandro Di Martino, Christian Hofer, Helmut Kern, Stefan Löfler, and et al. 2021. "Non-Coding RNAs in the Transcriptional Network That Differentiates Skeletal Muscles of Sedentary from Long-Term Endurance- and Resistance-Trained Elderly" International Journal of Molecular Sciences 22, no. 4: 1539. https://doi.org/10.3390/ijms22041539