Identification of Modulated MicroRNAs Associated with Breast Cancer, Diet, and Physical Activity
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. miRNA Microarray Expression Profiling Dataset Selection
2.2. Computational Identification of microRNAs Involved in Breast Cancer
2.3. Computational Identification of microRNA Modulated by Diet and Exercise
2.4. Breast Cancer (BC) miRNA Modulation of Epithelial-Mesenchymal Transition (EMT) Genes
2.5. microRNA Pathway Prediction Analysis and miRNA-Targeted Genes Protein–Protein Interaction
2.6. Overall Survival Predictive Value of BC, Exercise-Modulated, and Diet-Modulated microRNAs
3. Discussion
4. Materials and Methods
4.1. microRNA Expression Profiling Dataset Selection
4.2. Differential Analysis between Groups and microRNA Annotation
4.3. Identification of microRNAs Involved in Breast Cancer and Effectively Modulated by Diet and Exercise
4.4. Interaction between Selected microRNAs and Epithelial-Mesenchymal Transition (EMT) Genes
4.5. microRNA Pathway Prediction Analysis
4.6. miRNA-Targeted Genes Interaction and Gene Ontology (GO)
4.7. Prognostic Significance of Computationally Selected microRNAs
4.8. Statistical Analyses
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Series Accession | Number of Control | Number of BC Tissue | Total Number | Samples | Platform | Ref. |
---|---|---|---|---|---|---|
Breast Cancer Datasets | ||||||
GSE57897 | 31 | 422 | 453 | Normal and BC tissues | GPL18722 Homo sapiens microRNA array | [38] |
GSE97811 | 16 | 45 | 61 | Normal and BC FFPE tissues | GPL21263 3D-Gene Human miRNA V21_1.0.0 | [39] |
GSE58606 | 11 | 122 | 133 | Normal and BC FFPE tissues | GPL18838 miRCURY LNA microRNA Array 7th generation | [40] |
GSE38167 | 23 | 31 | 54 | Normal and BC FFPE tissues | GPL14943 Agilent-029297 Human miRNA Microarray | [41] |
GSE32922 | 15 | 22 | 37 | Normal and BC tissues | GPL7723 miRCURY LNA microRNA Array, v.11.0 | [42] |
GSE45666 | 15 | 101 | 116 | Normal and BC tissues | GPL14767 Agilent-021827 Human miRNA Microarray | [43] |
GSE26666 | 17 | 77 | 94 | Frozen normal and BC tissues | GPL8227 Agilent-019118 Human miRNA Microarray 2.0 | [44] |
GSE40525 | 59 | 61 | 120 | Normal and BC FFPE tissues | GPL8227 Agilent-019118 Human miRNA Microarray 2.0 | [45] |
Samples before Diet | Samples after Diet | Diet Datasets | ||||
GSE27474 | 14 | 14 | 28 | Serum Samples | GPL8179 Illumina Human v2 MicroRNA expression beadchip | [46] |
GSE87103 | 12 | 12 | 24 | Subcutaneous adipose tissues | GPL11434 miRCURY LNA microRNA Array, 6th generation | [47] |
GSE75026 | 12 | 12 | 24 | PBMCs samples | GPL8179 Illumina Human v2 MicroRNA expression beadchip | [48] |
Samples before Exercise | Samples after Exercise | Exercise Datasets | ||||
GSE133910 | 46 | 44 | 90 | Peripheral blood samples | GPL25134 Agilent-070156 Human_miRNA_V21.0_Microarray | [49] |
GSE87103 | 12 | 12 | 24 | Subcutaneous adipose tissues | GPL11434 miRCURY LNA microRNA Array, 6th generation | [47] |
GSE45041 | 10 | 10 | 20 | White blood cells | GPL16770 Agilent-031181 Unrestricted Human miRNA V16.0 | [50] |
GSE51837 | 12 | 12 | 24 | Monocytes | GPL10850 Agilent-021827 Human miRNA Microarray (V3) | [51] |
GSE41915 | 11 | 11 | 22 | NK cells | GPL10850 Agilent-021827 Human miRNA Microarray (V3) | [52] |
GSE28745 | 12 | 12 | 24 | PBMCs | GPL8227 Agilent-019118 Human miRNA Microarray 2.0 | [53] |
GSE18999 | 11 | 11 | 22 | Neutrophils | GPL7731 Agilent-019118 Human miRNA Microarray 2.0 | [54] |
miRNA | GEO Datasets log2FC Average | TCGA BRCA | |
---|---|---|---|
p-Value | |||
Upregulated miRNAs | |||
hsa-miR-103a-3p | 1.044 | 1.532 | 1.031 × 10−19 |
hsa-miR-106b-5p | 1.000 | 2.423 | 7.270 × 10−28 |
hsa-miR-107 | 0.882 | 1.676 | 3.424 × 10−17 |
hsa-miR-141-3p | 1.476 | 5.343 | 2.723 × 10−29 |
hsa-miR-142-3p | 1.775 | 3.040 | 2.214 × 10−18 |
hsa-miR-142-5p | 1.413 | 2.283 | 1.313 × 10−13 |
hsa-miR-146a-5p * | 0.902 | #N/D | #N/D |
hsa-miR-155-5p | 1.443 | 1.961 | 4.674 × 10−18 |
hsa-miR-15b-5p | 1.076 | 1.908 | 1.745 × 10−11 |
hsa-miR-16-5p | 0.955 | 1.591 | 2.960 × 10−8 |
hsa-miR-181b-5p | 0.616 | 2.219 | 1.238 × 10−22 |
hsa-miR-182-5p | 2.027 | 4.799 | 2.421 × 10−40 |
hsa-miR-183-5p | 2.759 | 7.102 | 3.388 × 10−47 |
hsa-miR-185-5p | 0.883 | 1.548 | 2.932 × 10−9 |
hsa-miR-18a-5p | 1.714 | 1.905 | 5.766 × 10−14 |
hsa-miR-200a-3p | 1.346 | 3.948 | 2.352 × 10−26 |
hsa-miR-200b-3p | 1.564 | 2.846 | 4.468 × 10−20 |
hsa-miR-200c-3p | 1.298 | 2.691 | 2.049 × 10−17 |
hsa-miR-203a-3p | 1.055 | 2.287 | 2.680 × 10−14 |
hsa-miR-21-5p | 2.054 | 4.448 | 5.680 × 10−41 |
hsa-miR-210-3p | 1.244 | 5.632 | 1.111 × 10−31 |
hsa-miR-25-3p * | 0.946 | #N/D | #N/D |
hsa-miR-301a-3p | 1.620 | 2.314 | 7.058 × 10−24 |
hsa-miR-340-5p | 0.924 | 2.001 | 8.384 × 10−25 |
hsa-miR-425-5p | 1.733 | 1.740 | 8.393 × 10−8 |
hsa-miR-429 | 1.751 | 4.884 | 6.208 × 10−33 |
hsa-miR-484 | 0.792 | 1.399 | 2.801 × 10−6 |
hsa-miR-7-5p | 1.786 | 1.850 | 7.483 × 10−21 |
hsa-miR-93-5p | 1.209 | 2.110 | 5.223 × 10−26 |
hsa-miR-96-5p | 2.178 | 6.970 | 7.515 × 10−47 |
Downregulated miRNAs | |||
hsa-miR-100-5p | −1.574 | −4.066 | 1.191 × 10−52 |
hsa-miR-1229-3p | −0.819 | 1.274 | 2.105 × 10−6 |
hsa-miR-125b-5p | −1.819 | −4.107 | 6.680 × 10−48 |
hsa-miR-130a-3p | −0.996 | −2.371 | 2.085 × 10−30 |
hsa-miR-139-3p | −1.178 | −8.512 | 2.131 × 10−52 |
hsa-miR-139-5p | −2.444 | −8.699 | 6.482 × 10−58 |
hsa-miR-143-3p | −1.422 | −2.288 | 1.458 × 10−28 |
hsa-miR-145-3p | −1.501 | −3.196 | 7.255 × 10−54 |
hsa-miR-145-5p | −2.015 | −5.892 | 2.501 × 10−50 |
hsa-miR-195-5p | −1.541 | −2.867 | 1.560 × 10−39 |
hsa-miR-202-3p * | −1.198 | #N/D | #N/D |
hsa-miR-205-5p | −2.033 | −5.921 | 4.198 × 10−35 |
hsa-miR-335-5p | −1.961 | −4.846 | 4.980 × 10−27 |
hsa-miR-376a-3p | −1.441 | −1.364 | 2.287 × 10−8 |
hsa-miR-377-3p | −1.542 | −1.418 | 2.186 × 10−7 |
hsa-miR-381-3p | −1.523 | −2.486 | 3.350 × 10−26 |
hsa-miR-486-5p | −1.496 | −10.611 | 3.737 × 10−26 |
hsa-miR-497-5p | −1.254 | −2.726 | 1.543 × 10−33 |
hsa-miR-99a-5p | −1.433 | −5.165 | 6.270 × 10−63 |
KEGG Pathway | p-Value | N. of Targeted Genes | Involved miRNAs |
---|---|---|---|
Pathways in cancer (hsa05200) | 4.05564 × 10−7 | 179 | 10 |
PI3K-Akt signaling pathway (hsa04151) | 0.011123026 | 140 | 10 |
Proteoglycans in cancer (hsa05205) | 2.21725 × 10−17 | 107 | 10 |
MAPK signaling pathway (hsa04010) | 0.011123026 | 104 | 10 |
Viral carcinogenesis (hsa05203) | 6.08511 × 10−8 | 95 | 10 |
Transcriptional misregulation in cancer (hsa05202) | 0.002760238 | 80 | 10 |
Hippo signaling pathway (hsa04390) | 1.31008 × 10−8 | 76 | 10 |
FoxO signaling pathway (hsa04068) | 1.48491 × 10−6 | 71 | 10 |
Cell cycle (hsa04110) | 3.14391 × 10−5 | 66 | 10 |
Insulin signaling pathway (hsa04910) | 0.009388457 | 65 | 10 |
AMPK signaling pathway (hsa04152) | 0.006097228 | 62 | 10 |
Thyroid hormone signaling pathway (hsa04919) | 0.000182888 | 61 | 10 |
HIF-1 signaling pathway (hsa04066) | 3.77879 × 10−5 | 57 | 10 |
TNF signaling pathway (hsa04668) | 0.014299582 | 54 | 10 |
Prostate cancer (hsa05215) | 2.74229 × 10−5 | 52 | 10 |
Small cell lung cancer (hsa05222) | 2.1672 × 10−5 | 50 | 10 |
Estrogen signaling pathway (hsa04915) | 0.00014031 | 47 | 10 |
ErbB signaling pathway (hsa04012) | 0.001313884 | 45 | 9 |
Chronic myeloid leukemia (hsa05220) | 1.45098 × 10−6 | 44 | 10 |
Renal cell carcinoma (hsa05211) | 1.69642 × 10−7 | 42 | 10 |
TGF-beta signaling pathway (hsa04350) | 4.62474 × 10−6 | 41 | 10 |
Pancreatic cancer (hsa05212) | 9.61555 × 10−6 | 40 | 10 |
Colorectal cancer (hsa05210) | 5.0244 × 10−7 | 39 | 10 |
p53 signaling pathway (hsa04115) | 0.00014031 | 39 | 10 |
Apoptosis (hsa04210) | 0.018765462 | 38 | 10 |
Glioma (hsa05214) | 2.56338 × 10−6 | 37 | 10 |
Central carbon metabolism in cancer (hsa05230) | 2.56338 × 10−6 | 36 | 10 |
Non-small cell lung cancer (hsa05223) | 8.72499 × 10−6 | 34 | 10 |
ECM-receptor interaction (hsa04512) | 1.96805 × 10−5 | 34 | 10 |
mTOR signaling pathway (hsa04150) | 0.003253273 | 34 | 10 |
Melanoma (hsa05218) | 0.009412459 | 34 | 10 |
Endometrial cancer (hsa05213) | 3.18028 × 10−5 | 32 | 10 |
Acute myeloid leukemia (hsa05221) | 0.019544711 | 29 | 10 |
Bladder cancer (hsa05219) | 0.000423154 | 25 | 9 |
Thyroid cancer (hsa05216) | 0.000804104 | 17 | 10 |
KEGG Pathway | p-Value | N. of Targeted Genes | Involved miRNAs |
---|---|---|---|
Adherens junction (hsa04520) | 0.00127981 | 10 | 2 |
Choline metabolism in cancer (hsa05231) | 0.0417592 | 10 | 2 |
Epithelial cell signaling in Helicobacter pylori infection (hsa05120) | 0.04463459 | 9 | 3 |
Colorectal cancer (hsa05210) | 0.02665458 | 8 | 2 |
Glioma (hsa05214) | 0.02665458 | 7 | 3 |
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Falzone, L.; Grimaldi, M.; Celentano, E.; Augustin, L.S.A.; Libra, M. Identification of Modulated MicroRNAs Associated with Breast Cancer, Diet, and Physical Activity. Cancers 2020, 12, 2555. https://doi.org/10.3390/cancers12092555
Falzone L, Grimaldi M, Celentano E, Augustin LSA, Libra M. Identification of Modulated MicroRNAs Associated with Breast Cancer, Diet, and Physical Activity. Cancers. 2020; 12(9):2555. https://doi.org/10.3390/cancers12092555
Chicago/Turabian StyleFalzone, Luca, Maria Grimaldi, Egidio Celentano, Livia S. A. Augustin, and Massimo Libra. 2020. "Identification of Modulated MicroRNAs Associated with Breast Cancer, Diet, and Physical Activity" Cancers 12, no. 9: 2555. https://doi.org/10.3390/cancers12092555