Whole Genome Expression Analyses of miRNAs and mRNAs Suggest the Involvement of miR-320a and miR-155-3p and their Targeted Genes in Lithium Response in Bipolar Disorder
Abstract
:1. Introduction
2. Results
2.1. Genome-Wide Analysis of miRNAs and mRNAs
2.2. Correlation between miRNAs and mRNAs Expression Levels
2.3. Validation of Selected miRNAs-mRNAs Pairs with qRT-PCR
3. Discussion
4. Materials and Methods
4.1. Sample
4.2. LCLs and In Vitro Lithium Treatment
4.3. Genome-Wide NGS Analysis of miRNAs
4.4. Genome-Wide Microarray Analysis of mRNAs
4.5. Validation with Quantitative Reverse Transcription-PCR (qRT-PCR)
4.6. Data Analysis
4.6.1. Genome-Wide Analysis NGS of miRNAs
4.6.2. Genome-Wide Analysis of mRNAs
4.6.3. Correlation between miRNA and mRNA Expression Levels
4.6.4. Validation with qRT-PCR
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AUTS2 | Activator of Transcription and Developmental Regulator |
BD | Bipolar disorder |
cAMP | Cyclic AMP |
CAPNS1 | Calpain Small Subunit 1 |
BH | Benjamini–Hochberg |
BHLHE40 | Basic Helix-Loop-Helix Family Member E40 |
cDNA | Complementary DNA |
ConLiGen | Consortium on Lithium Genetics |
DE | Differentially expressed |
CPM | Counts per million |
dUTP | 2’-Deoxyuridine 5’-Triphosphate |
ER | Excellent responders |
FC | Fold change |
FDR | False discovery rate |
GAPDH | Glyceraldehyde-3-Phosphate Dehydrogenase |
GWAS | Genome-wide association study |
KYAT1 | Kynurenine Aminotransferase 1 |
LCL | Lymphoblastoid cell lines |
LiCl | Lithium chloride |
MDD | Major depressive disorder |
mRNA | Messenger RNA |
miRNA | microRNA |
NGS | Next generation sequencing |
NR | Non-responders |
NTC | No-template controls |
qRT-PCR | Quantitative reverse transcription-PCR |
RDC | Research Diagnostic Criteria |
RHOA | Ras Homolog Family Member A |
RNU6B | RNA, U6 Small Nuclear 6, Pseudogene |
RGS16 | Regulator of G Protein Signaling 16 |
SCZ | Schizophrenia |
SNP | Single nucleotide polymorphisms |
SP4 | Sp4 Transcription Factor |
SADS-L | Schedule for Affective Disorder and Schizophrenia Lifetime Version |
SD | Standard deviation |
SP4 | Sp4 Transcription Factor |
TS | Total score |
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miRNA | FC | p | FDR q |
---|---|---|---|
hsa-miR-320a | 0.55 | 3.2 × 10−10 | 3.8 × 10−8 |
hsa-miR-125a-5p | 0.16 | 6.6 × 10−8 | 3.9 × 10−6 |
hsa-miR-148a-3p | 2.23 | 1.2 × 10−7 | 4.9 × 10−6 |
hsa-miR-574-3p | 0.32 | 5.4 × 10−7 | 1.6 × 10−5 |
hsa-miR-1273h-3p | 0.49 | 3.5 × 10−5 | 0.0008 |
hsa-miR-22-3p | 1.79 | 7.2 × 10−5 | 0.0014 |
hsa-miR-9-5p | 0.57 | 0.0001 | 0.0019 |
hsa-miR-26b-5p | 1.78 | 0.0001 | 0.0019 |
hsa-miR-378a-5p | 0.43 | 0.0002 | 0.0030 |
hsa-miR-223-3p | 4.13 | 0.0003 | 0.0030 |
hsa-miR-155-3p | 2.27 | 0.0003 | 0.0031 |
hsa-miR-505-3p | 0.50 | 0.0005 | 0.0043 |
hsa-miR-744-5p | 1.59 | 0.0005 | 0.0043 |
hsa-let-7e-5p | 0.32 | 0.0005 | 0.0043 |
hsa-miR-138-5p | 0.32 | 0.0006 | 0.0044 |
hsa-miR-181a-3p | 2.61 | 0.0006 | 0.0044 |
hsa-miR-15a-5p | 1.62 | 0.0006 | 0.0044 |
hsa-miR-941 | 0.54 | 0.0007 | 0.0045 |
hsa-miR-148b-3p | 2.32 | 0.0007 | 0.0045 |
hsa-miR-652-3p | 0.46 | 0.0008 | 0.0049 |
hsa-miR-130b-3p | 0.69 | 0.0009 | 0.0050 |
hsa-miR-15b-3p | 1.81 | 0.0013 | 0.0068 |
hsa-miR-345-5p | 0.56 | 0.0014 | 0.0070 |
hsa-miR-454-5p | 2.14 | 0.0019 | 0.0096 |
hsa-miR-4677-3p | 2.51 | 0.0021 | 0.0102 |
hsa-miR-374a-3p | 1.74 | 0.0024 | 0.0111 |
hsa-miR-19b-3p | 1.59 | 0.0029 | 0.0125 |
hsa-let-7d-3p | 0.71 | 0.0030 | 0.0125 |
hsa-miR-181d-5p | 0.55 | 0.0034 | 0.0136 |
hsa-miR-101-3p | 1.76 | 0.0035 | 0.0136 |
hsa-miR-629-5p | 0.46 | 0.0036 | 0.0136 |
hsa-miR-574-5p | 0.49 | 0.0039 | 0.0144 |
hsa-miR-378a-3p | 0.68 | 0.0042 | 0.0150 |
hsa-miR-148a-5p | 1.61 | 0.0044 | 0.0152 |
hsa-miR-142-3p | 1.47 | 0.0045 | 0.0152 |
hsa-miR-454-3p | 1.45 | 0.0050 | 0.0163 |
hsa-miR-142-5p | 1.58 | 0.0051 | 0.0163 |
hsa-miR-598-3p | 0.51 | 0.0052 | 0.0163 |
hsa-let-7f-5p | 1.33 | 0.0054 | 0.0163 |
hsa-miR-27a-5p | 1.66 | 0.0084 | 0.0241 |
hsa-let-7a-5p | 1.29 | 0.0085 | 0.0241 |
hsa-miR-210-5p | 1.41 | 0.0087 | 0.0241 |
hsa-miR-30e-3p | 1.43 | 0.0087 | 0.0241 |
hsa-miR-146a-5p | 1.95 | 0.0117 | 0.0315 |
hsa-miR-23a-3p | 0.73 | 0.0131 | 0.0346 |
hsa-miR-15b-5p | 1.39 | 0.0149 | 0.0385 |
hsa-miR-425-5p | 0.73 | 0.0171 | 0.0430 |
hsa-miR-197-3p | 0.71 | 0.0182 | 0.0450 |
hsa-miR-335-3p | 3.38 | 0.0204 | 0.0489 |
hsa-miR-421 | 1.34 | 0.0208 | 0.0489 |
hsa-miR-26a-5p | 1.34 | 0.0210 | 0.0489 |
hsa-miR-194-5p | 0.60 | 0.0215 | 0.0490 |
NGS/Microarray | qRT-PCR | ||||
---|---|---|---|---|---|
FC | p | FDR q | FC | p | |
miRNA | |||||
hsa-miR-320a | 0.55 | 3.2 × 10−10 | 3.8 × 10−8 | 0.51 | 3.2 × 10−5 |
hsa-miR-155-3p | 2.27 | 0.0003 | 0.0031 | 1.70 | 0.003 |
hsa-mir-138 | 0.32 | 0.0006 | 0.0044 | 0.63 | 0.180 |
mRNA | |||||
CAPNS1 | 1.21 | 9.2 × 10−5 | 0.0021 | 1.59 | 0.040 |
RGS16 | 1.52 | 1.3 × 10−5 | 0.0006 | 1.42 | 0.017 |
BHLHE40 | 1.37 | 2.4 × 10−6 | 0.0002 | 1.05 | 0.167 |
RHOA | 1.11 | 3.1 × 10−5 | 0.0010 | 1.60 | 0.556 |
SP4 | 0.68 | 2.9 × 10−5 | 0.0001 | 0.43 | 0.053 |
KYAT1 | 0.75 | 1.5 × 10−8 | 7.2 × 10−6 | 0.43 | 0.065 |
AUTS2 | 0.43 | 8.5 × 10−5 | 0.0020 | 1.71 | 0.250 |
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Pisanu, C.; Merkouri Papadima, E.; Melis, C.; Congiu, D.; Loizedda, A.; Orrù, N.; Calza, S.; Orrù, S.; Carcassi, C.; Severino, G.; et al. Whole Genome Expression Analyses of miRNAs and mRNAs Suggest the Involvement of miR-320a and miR-155-3p and their Targeted Genes in Lithium Response in Bipolar Disorder. Int. J. Mol. Sci. 2019, 20, 6040. https://doi.org/10.3390/ijms20236040
Pisanu C, Merkouri Papadima E, Melis C, Congiu D, Loizedda A, Orrù N, Calza S, Orrù S, Carcassi C, Severino G, et al. Whole Genome Expression Analyses of miRNAs and mRNAs Suggest the Involvement of miR-320a and miR-155-3p and their Targeted Genes in Lithium Response in Bipolar Disorder. International Journal of Molecular Sciences. 2019; 20(23):6040. https://doi.org/10.3390/ijms20236040
Chicago/Turabian StylePisanu, Claudia, Eleni Merkouri Papadima, Carla Melis, Donatella Congiu, Annalisa Loizedda, Nicola Orrù, Stefano Calza, Sandro Orrù, Carlo Carcassi, Giovanni Severino, and et al. 2019. "Whole Genome Expression Analyses of miRNAs and mRNAs Suggest the Involvement of miR-320a and miR-155-3p and their Targeted Genes in Lithium Response in Bipolar Disorder" International Journal of Molecular Sciences 20, no. 23: 6040. https://doi.org/10.3390/ijms20236040