Table S1. List of miRNAs that were significantly dysregulated in

0 downloads 0 Views 1MB Size Report
miR-let-7b. 0.42. miR-let-7c. 3.16. miR-let-7d. 2.05. miR-let-7e. 0.29. 0.47. 0.34. miR-let-7f-1. 0.47. miR-let-7f-2. 0.41. miR-1a-1. 0.20. 0.08. 0.13. 0.34. 3.66. 3.02.
Table S1. List of miRNAs that were significantly dysregulated in organs and body fluids of mice exposed to MCS. The values indicate the MCS/Sham ratio, as assessed by microarray and volcano-plot analyses. miRNA

Lung

miR-let-7b miR-let-7c miR-let-7d miR-let-7e miR-let-7f-1 miR-let-7f-2 miR-1a-1 miR-7-3p miR-7a miR-7a-2 miR-7b miR-9-3p miR-9-5p miR-10a miR-10b miR-15a miR-16 miR-16-2 miR-18a miR-18b miR-19b miR-19b-1 miR-21 miR-21a miR-22 miR-23a-3p

0.42

Liver

Heart

Kidney

Spleen

Urinary bladder

Skeletal muscle

Colon

Stomach

Brain

Blood serum

BALF

Urine

3.16 2.05 0.29 0.47 0.41 0.20

0.47

0.08 2.25 2.68

0.34

0.13

0.34

0.28 0.41 0.37

3.66

3.02

6.42 2.35

1.54 0.51

2.16 3.55

0.54

0.48 0.36

0.30

0.21

0.27 2.71

0.41 2.77 0.45 0.30 0.30 0.44 0.46 0.43 0.35

0.15 3.30

0.16 0.09

0.21

0.45 2.43

0.60 1.50

0.41

miR-23a-5p miR-23b miR-24 miR-25 miR-26a-1 miR-26a-2 miR-26b miR-27a miR-27b miR-28 miR-28a miR-28b miR-29a miR-29b miR-29b-1 miR-29c miR-30a miR-30b-3p miR-30b-5p miR-30c-1-3p miR-30c-2-3p miR-30c-5p miR-30e miR-31 miR-32 miR-33a miR-34b miR-34c miR-92a miR-92a-2 miR-93 miR-96 miR-98

0.13 0.38

0.28

0.24

0.19

0.24

0.18

0.46

0.12 2.22 0.43 0.34

0.51 0.40 0.63

2.45 0.21

0.10 0.32

0.49

1.60 0.23

0.29 0.39 0.37 0.49 0.33 0.46 0.35 0.27 0.21 0.31

1.60

0.31

2.07

2.97

0.46 0.46

5.61 3.47 0.24

2.68

0.66

2.78 0.20

1.72

5.18

2.14

1.56

2.55 0.43 0.50

3.04 0.40

0.28 0.06 0.57 0.27

1.89

0.24 2.07 4.68

3.39 0.29 0.08

1.93 0.66

miR-99b-3p miR-99b-5p miR-101b miR-106b miR-107 miR-122 miR-125a-3p miR-125a-5p miR-125b-1 miR-125b-2 miR-126 miR-129 miR-129-5p miR-129-1-3p miR-129-2 miR-130a miR-130b miR-132-3p miR-132-5p miR-133b miR-135a-5p miR-135b miR-136 miR-137 miR-138-1 miR-138-2 miR-139 miR-141 miR-142 miR-144 miR-146a miR-147b miR-148b-3p

0.28 0.29

4.72 3.45 4.03

0.35

0.54

0.35 0.44

2.36 4.43 0.19

0.40

7.42

3.53

2.12

6.95

0.31 5.04 6.48

5.60 6.66

3.97

0.60

0.41

0.35

0.59

4.44 9.16

3.12 5.12

4.35

4.35

1.74

2.87 4.16 0.41 0.27 0.33 0.41 0.37 0.29 0.29 0.37

7.83 2.75

9.98

1.73

0.47 0.37

0.49 0.35

1.75 0.49

22.35 6.87

0.41

0.29 0.47

0.30 0.47 0.49 0.12

3.89 8.21 0.15 2.88

0.40 7.39

7.33

0.60

1.96

miR-149-3p miR-150 miR-151 miR-152 miR-153 miR-154 miR-155 miR-181 miR-181a miR-181b miR-181c miR-181d miR-182 miR-183 miR-184 miR-185-3p miR-185-5p miR-186 miR-187-5p miR-188-3p miR-188-5p miR-190a miR-191-3p miR-191-5p miR-192 miR-193a-3p miR-193a-5p miR-193b miR-194-3p miR-195 miR-196a-3p miR-196a-1-3p miR-196b

0.14

0.27 2.40 2.13

2.08 2.64

1.51 4.26 0.08

4.24 0.12

0.11

2.67

3.02 2.10

2.36

2.27 0.06 0.22 0.29 0.13 0.12

0.33 2.54

1.87

3.77 2.96 0.32 0.38

0.42 0.48

0.46 0.31

3.33

0.38 0.27

0.47

0.63

3.21 0.40 0.20

0.06

0.05

2.32

3.33

2.83 2.86 0.31 0.44 0.30 3.06 0.42 0.26 0.21

2.19 0.18

0.49 0.42

8.25 4.46

6.47 4.23

0.30 0.20 0.34 8.69

1.62

0.65 1.53

1.54

miR-199a miR-199b miR-200b miR-200c miR-201 miR-202-3p miR-202-5p miR-204 miR-205-5p miR-206 miR-207 miR-208b miR-211 miR-214 miR-215 miR-216a miR-216b miR-217 miR-218 miR-218-1 miR-219 miR-223-5p miR-290 miR-291a miR-291b miR-292 miR-293 miR-294 miR-295 miR-296 miR-297a miR-297c miR-298-3p

0.45 0.44 2.24 0.47 0.13 0.34 5.27 5.52

0.40 2.48

1.89

1.82

7.19 0.47 7.51

3.41

4.70

2.77

5.00

0.11

4.96 2.21

0.48 3.27 0.40

0.55 0.46

4.12 0.33 0.22 0.47 0.41 0.38 0.30 0.46 0.40 0.50

0.25 8.08

6.96

8.77

5.53

0.40

5.77

1.66

0.46 0.51

0.43

0.39

0.41 2.32

2.70

4.20

2.35

2.97 0.28 2.91 0.54

0.31

0.29 0.24

1.55

2.03 5.09

0.22

0.23

6.42

3.07

0.38 0.41 3.90 3.39

3.12

0.62 2.21 1.92

0.36

miR-298-5p miR-299a miR-300 miR-301a miR-301b miR-302a miR-302b miR-302c miR-307 miR-320 miR-320a miR-322 miR-323a miR-324 miR-325 miR-328 miR-329 miR-330 miR-331-3p miR-331-5p miR-335-3p miR-335-5p miR-337 miR-338 miR-339 miR-340-3p miR-340-5p miR-341-3p miR-344 miR-344d-5p miR-344d-3p miR-344d-1 miR-344d-3

0.42 3.11

0.40

0.03

0.08 5.88

4.82

1.63

3.47 0.16 0.11

2.64 0.12 2.05 3.11 0.32

0.11

7.82

1.53

2.51 0.31 4.76 0.13

0.49

0.36

0.46 0.33 3.23 0.51

0.21 0.19

0.33 0.49 2.84 0.47 0.21 4.59 13.42

0.13

0.10 0.43

17.40

17.58 0.22

0.34

0.42

0.30 2.17

5.13 2.27

0.37 2.11

0.16 2.00 3.23 3.10 2.39 0.31

0.38

0.45

0.37

0.60

miR-344e miR-344g miR-345 miR-346-3p miR-346-5p miR-350 miR-351-3p miR-351-5p miR-361 miR-363 miR-365a miR-367 miR-369 miR-370 miR-374b miR-376b miR-377-3p miR-378a-3p miR-378a-5p miR-378b miR-379 miR-380-3p miR-380-5p miR-381 miR-382 miR-384 miR-411 miR-421 miR-423 miR-425 miR-429 miR-431-3p miR-431-5p

0.43

0.39 2.01

0.23 0.48 0.22 0.40 0.09

0.43 0.19

0.40 0.42

0.17

0.50 0.27 0.47

0.17

0.22 0.33

0.25 0.43 0.50

0.20

0.36

0.38

0.43

0.49 0.61

0.34 4.90 0.37 3.51

4.22 0.39

0.07

3.74

0.28

0.50

0.42

0.24 0.28 0.20 0.44 0.33 0.13

1.52

3.17 0.40 2.95

0.39

0.65 8.98 0.49

5.60 0.49 0.24

0.47

0.27

0.34

0.61

0.56

0.66

4.63 0.07 0.13 0.33 0.44 0.42

6.09 0.06

1.64 2.62

0.60 1.71 1.59 0.65

miR-433 miR-434 miR-448 miR-449c miR-450a miR-450a-1 miR-450b-3p miR-450b-5p miR-451a miR-452 miR-453 miR-455 miR-463 miR-465a miR-465b miR-465c miR-466a miR-466b miR-466c miR-466d miR-466e miR-466f miR-466h-3p miR-466h-5p miR-466i-3p miR-466i-5p miR-466j miR-466k miR-466l miR-466m miR-466n miR-466o miR-466q

0.14 0.36 0.37 0.44

0.12

0.41

0.44

0.26

0.18

0.37

2.08 0.42

0.27

0.47

0.60

0.27 0.16 0.29

5.60

2.18 2.85

3.81

0.51

5.59 0.48 2.22 0.36 0.28

1.67 0.30 0.34 7.43

2.66

0.28

0.36

0.29

0.36

0.28 4.95 0.12 0.13 3.30 4.98 0.21

0.26 0.30

0.16

0.28

0.44

0.28 0.27 0.28 0.44

0.34 0.13 0.48

0.43 0.44 0.39

0.30 0.22 0.19 0.14 0.27

0.41

0.32

3.08 2.77

4.37

0.15

0.40 0.49 0.12 0.22

0.30

0.47

0.40 0.49

0.47

0.23 0.46

0.12

0.16

3.00

0.65 2.11 1.90 2.98 1.81 1.51 2.15 1.92 1.55 2.39 3.07 1.76 1.76

1.83

0.59

2.03

7.09

1.86

0.52

miR-467a miR-467b miR-467c miR-467d miR-467e miR-467f miR-467g miR-467h miR-470 miR-471 miR-484 miR-485 miR-486 miR-488 miR-489 miR-490-3p miR-490-5p miR-491-3p miR-491-5p miR-493 miR-494 miR-495-3p miR-495-5p miR-496 miR-496a miR-497 miR-499a miR-500 miR-501 miR-503 miR-504 miR-505 miR-509

0.28 0.16 0.13

2.58

0.21 0.23 0.17

3.95 4.10 4.86 4.43

0.32

5.33 4.31 4.44

2.15 2.17 1.79 2.14

0.27 0.28

3.45 3.75 3.58 0.34

0.32 5.02

0.29

2.37 0.34 0.42

0.17

0.46

2.50 2.06

0.45

0.39

1.96 2.27 2.65 0.42 0.58

0.35 0.32

0.50

0.31 7.54 0.34 0.35 0.33 0.18 0.43

0.24

0.21 0.39

10.78 3.48

2.85 0.41 0.25 0.19

14.76

0.26 0.27

18.02

0.48

0.62 0.24 3.99 3.40 0.20 0.25

0.50

1.82

1.58

6.28 3.35 0.48

0.65

0.61

2.27 0.32 4.81 0.40

1.54 0.34

0.31

0.55 0.62

0.16

miR-511-3p miR-511-5p miR-532 miR-539 miR-540 miR-541 miR-542-3p miR-542-5p miR-543 miR-544 miR-551b miR-574 miR-582 miR-590 miR-592 miR-598 miR-615 miR-652 miR-653 miR-654 miR-664 miR-665 miR-667 miR-668 miR-668l miR-669a miR-669a-3 miR-669b miR-669c miR-669d-3p miR-669d-5p miR-669e miR-669f

4.55

3.17

0.66

4.26 0.42

1.67 2.93

3.90

1.84

4.48 6.67 2.86 0.15 0.10 2.12 6.01

0.49

0.36 0.07 0.08 0.35 0.29 0.47 2.91 0.40 0.30 0.02 0.42

1.62

0.25

4.35

2.27 9.02

3.74

3.37

2.20

0.61

2.92

0.62

1.91

0.36 0.09

2.37

0.23 3.72

0.39 2.43 5.71

3.42 5.84

6.03 5.65

0.12

2.96 4.55 0.16 0.23

0.66 0.61

0.69

0.46 0.31 0.24 0.46 2.57 2.53 4.00 4.23

2.94 4.71 2.13

0.29

2.27

2.01 0.25

4.23 6.40 3.13 4.59 3.70 4.17 2.52 4.40

3.25 4.07 2.86

2.14 2.10 1.63 2.59

3.75

2.23 2.58

0.44

miR-669g miR-669h miR-669k miR-669m miR-669n miR-669p miR-670 miR-673 miR-675 miR-676-3p miR-676-5p miR-677 miR-678 miR-679-3p miR-679-5p miR-686 miR-688 miR-690 miR-691 miR-692 miR-694 miR-695 miR-696 miR-697 miR-700 miR-701-3p miR-701-5p miR-702-5p miR-703 miR-704 miR-705 miR-706 miR-707

0.29

2.74 0.20 0.33

0.29 0.34

4.65 0.45 0.35 0.08 0.21 0.30

3.32 6.67 3.52 5.00 4.80 0.27 3.01

2.70

0.39 1.58 4.05

2.08

0.61

0.62

0.47 0.54 0.25 3.12 0.18

0.38

3.46 0.31

2.24 0.25

0.13 0.34 0.43 0.10

0.42 0.31 0.12

2.33

0.47 0.31

0.18 1.52 0.28 0.34

0.22

3.83

0.65

8.66 0.24

4.38

2.50 0.22

0.19

0.30

0.17 0.28 3.55

0.38 2.03 0.13 0.35 0.33

0.08

0.25

0.37

miR-708 miR-709 miR-710 miR-711 miR-712 miR-713 miR-714 miR-717 miR-718 miR-719 miR-721 miR-742-3p miR-743a miR-758 miR-759 miR-761 miR-762 miR-764-3p miR-770 miR-802 miR-804 miR-871 miR-872 miR-874 miR-875 miR-876 miR-877 miR-878 miR-879 miR-880 miR-881 miR-882 miR-883a

0.44 3.70 0.08

6.67

7.14

7.49

0.64

5.87 0.26

0.60

4.23

0.65

8.33 0.41

0.47 0.18 3.26 0.36 0.30

3.63

0.21 4.98

0.26 0.30 3.23

0.36

0.41

0.47 4.36

0.32

0.42 2.94

0.32 0.23 2.63 0.30 0.27

0.45 0.19

3.46 2.29

0.20 0.14 0.31

0.13

0.19 0.13

0.51

0.34 0.19

0.26

2.36 5.23 3.27

2.71 3.36

0.47 4.63 2.85

0.11

3.96 4.98 0.29 7.11

0.63 0.53 0.63 0.59

0.44 0.34 0.45 0.35

2.44

0.09

5.52

3.91

0.33 2.38 0.14 0.19 0.21

0.25

0.56

miR-883b miR-1186b miR-1187 miR-1190 miR-1192 miR-1193 miR-1194 miR-1198 miR-1199 miR-1224-3p miR-1224-5p miR-1251 miR-1264 miR-1298 miR-1306

0.08 1.97

4.43

0.43

0.48

0.39 3.27

1.62

0.42 0.29 0.47

21.05 0.13

18.05 0.22

3.10

2.82

2.32

0.25 4.02

0.30 0.22 0.45

0.39 0.42 0.47

0.48 3.52 0.23

0.36 0.59

0.49

0.17

2.03 0.59

0.48

3.02

Fig. 1S. MA plots showing the effect of MCS on the expression profiles of 1135 miRNAs in the 10 mouse organs and 3 body fluids examined. The Y axis (M) reports the MCS/Sham log transformed data (log-intensity ratios). The X axis (A) reports the average MCS/Sham (amplitude of combined intensities) of log transformed data (log-intensity averages). Each green dot represents the expression intensity of each miRNA according to M and A. Red lines indicate the medians of data distribution according to miRNA expression levels.

Fig. 2S. Scatter-plot analyses comparing, for each one of the 10 examined organs and 3 body fluids, the miRNA expression in sham-exposed mice (Y axis) and MCS-exposed mice (X axis). The blue dots refer to 1928 human miRNAs (hsa or Homo sapiens), whereas the green dots refer to 1135 mouse miRNAs (mmu or Mus musculus). Dots falling outside the diagonal two-fold variation intervals (diagonal green lines) correspond to miRNAs dysregulated more than two-fold in their expression by MCS. Upregulated miRNAs are located in the lower-right area and downregulated miRNAs are in the upper-left area.

Fig. 3S. Volcano-plot analyses showing modulation by MCS of 1135 miRNAs in 10 organs and 3 body fluids of mice. Each dot corresponds to a miRNA. The dots are positioned in the graphs depending on the fold-variation (X axis, MCS/Sham ratio) and on the statistical significance calculated by ANOVA (Y axis). The red dots refer to those miRNAs that were dysregulated by MCS more than 2-fold and to a statistically significant extent (P < 0.05).