Volinia et al. 10.1073/pnas.0510565103.

Supporting Information

Files in this Data Supplement:

Supporting Figure 4
Supporting Table 3
Supporting Table 4
Supporting Table 5
Supporting Table 6
Supporting Table 7
Supporting Table 8
Supporting Table 9
Supporting Table 10
Supporting Table 11
Supporting Table 12
Supporting Table 13
Supporting Table 14






Fig. 4. Unsupervised analysis of microRNA expression data. MicroRNA profiling of 540 samples covering breast, colon, lung, pancreas, prostate and stomach normal tissues and tumors were filtered, and centred and normalized for each feature. The data were subject to hierarchical clustering on both the samples (horizontally oriented) and the features (vertically oriented), with probe names on the left, with average-linkage and Pearson correlation as a similarity measure. Sample names are indicated on the top and miRNA names on the left. In parenthesis is indicated the probe ID, since the same microRNA can have been measured by different oligonucleotides.





Table 3. Samples used in the study (tumors and corresponding normals)

Tumor type

Cancer samples

Normal samples

Lung carcinoma

123

123

Breast carcinoma

79

6*

Colon carcinoma

46

8

Gastric carcinoma

20

21

Endocrine pancreatic tumours

39

12

Prostate cancer

56

7

All tissues

363

177

* Pools of five unrelated normal breast tissues each (for a total of 30 unrelated individuals)





Table 4. Deregulated microRNAs in solid common cancers

Cancer

PAM up-regulated

SAM up-regulated

PAM down-regulated

SAM down-regulated

Breast

15

3 (FDR=0.33)

12

47

Colon

21

42 (FDR<=0.06)

1

5

Lung

35

38 (FDR<=0.01)

3

3

Pancreas

55

50 (FDR<=0.01)

2

8

Stomach

22

22 (FDR=0.06)

6

4

Prostate

39

49 (FDR=0.06)

6

3

Prediction analysis of microarrays (PAM) identifies those genes which best characterize cancers and normal tissues, whilst significance analysis of microarrays (SAM) all those which have differential expression in the two classes. False detection rates computed in SAM (FDR) are indicated in parentheses.





Table 5. MicroRNAs selected by prediction analysis of microarray (PAM) in breast (cancer vs. normal tissues)

miRNA (ID)

Breast cancer score

Breast normal score

miR-21 (47)

0.0331

-0.4364

miR-29b-2 (95)

0.0263

-0.3467

miR-146 (144)

0.0182

-0.2391

miR-125b-2 (111)

-0.0174

0.2286

miR-125b-1 (109)

-0.0169

0.222

miR-10b (32)

-0.0164

0.2166

miR-145 (143)

-0.0158

0.2076

miR-181a (158)

0.0153

-0.201

miR-140 (136)

-0.0122

0.1613

miR-213 (160)

0.0116

-0.1527

miR-29a prec (63)

0.0109

-0.1441

miR-181b-1 (210)

0.0098

-0.1284

miR-199b (194)

0.0089

-0.1172

miR-29b-1 (64)

0.0084

-0.1111

miR-130a (120)

-0.0076

0.1001

miR-155 (157)

0.0072

-0.0951

let-7a-2 (3)

-0.0042

0.0554

miR-205 (201)

-0.004

0.0533

miR-29c (65)

0.0032

-0.0423

miR-224 (228)

-0.003

0.0399

miR-100 (91)

-0.0021

0.0283

miR-31 (73)

0.0017

-0.022

miR-30c (70)

-7.00E-04

0.009

miR-17-5p (41)

7.00E-04

-0.0089

miR-210 (205)

4.00E-04

-0.0057

miR-122a (101)

4.00E-04

-0.005

miR-16-2 (39)

-1.00E-04

0.0013

Twenty-seven miRs selected, misclassification error after cross validation of 0.08. Fifteen overexpressed miRs in cancer are indicated by positive cancer scores; 12 down-regulated miRs are indicated by negative cancer scores.





Table 6. MicroRNAs selected by prediction analysis of microarray (PAM) in colon (cancer vs. normal tissues)

miRNA (ID)

Colon cancer score

Colon normal score

miR-24-1 (52)

0.0972

-0.5589

miR-29b-2 (95)

0.0669

-0.3845

miR-20a (46)

0.0596

-0.3424

miR-10a (30)

0.0511

-0.2938

miR-32 (75)

0.0401

-0.2306

miR-203 (197)

0.0391

-0.2251

miR-106a (99)

0.0364

-0.2094

miR-17-5p (41)

0.0349

-0.2005

miR-30c (70)

0.0328

-0.1888

miR-223 (227)

0.0302

-0.1736

miR-126* (102)

0.0199

-0.1144

miR-128b (115)

0.0177

-0.102

miR-21 (47)

0.0162

-0.0929

miR-24-2 (54)

0.0145

-0.0835

miR-99b prec (88)

0.0125

-0.0721

miR-155 (157)

0.0092

-0.0528

miR-213 (160)

0.0091

-0.0522

miR-150 (148)

0.0042

-0.0243

miR-107 (100)

0.003

-0.0173

miR-191 (177)

0.0028

-0.0159

miR-221 (224)

0.002

-0.0116

miR-9-3 (28)

-0.0014

0.0083

Twenty-two miRs selected, misclassification error after cross validation of 0.09. Twenty-one overexpressed miRs in cancer are indicated by positive cancer scores; one down-regulated miR is indicated by negative cancer scores.





Table 7. MicroRNAs selected by prediction analysis of microarray (PAM) in lung (cancer vs. normal tissues)

miRNA (ID)

Lung cancer score

Lung normal score

miR-21 (47)

0.175

-0.175

miR-205 (201)

0.1317

-0.1317

miR-200b (195)

0.1127

-0.1127

miR-9-1 (24)

0.1014

-0.1014

miR-210 (205)

0.0994

-0.0994

miR-148 (146)

0.0737

-0.0737

miR-141 (137)

0.0631

-0.0631

miR-132 (121)

0.0586

-0.0586

miR-215 (213)

0.0575

-0.0575

miR-128b (115)

0.0559

-0.0559

let-7g (15)

0.0557

-0.0557

miR-16-2 (39)

0.0547

-0.0547

miR-129-1/2 prec (118)

0.0515

-0.0515

miR-126* (102)

-0.0406

0.0406

miR-142-as (139)

0.0366

-0.0366

miR-30d (72)

-0.0313

0.0313

miR-30a-5p (66)

-0.0297

0.0297

miR-7-2 (21)

0.0273

-0.0273

miR-199a-1 (191)

0.0256

-0.0256

miR-127 (112)

0.0254

-0.0254

miR-34a prec (79)

0.0214

-0.0214

miR-34a (78)

0.0188

-0.0188

miR-136 (130)

0.0174

-0.0174

miR-202 (196)

0.0165

-0.0165

miR-196-2 (188)

0.0134

-0.0134

miR-199a-2 (192)

0.0126

-0.0126

let-7a-2 (3)

0.0109

-0.0109

miR-124a-1 (104)

0.0081

-0.0081

miR-149 (147)

0.0079

-0.0079

miR-17-5p (41)

0.0061

-0.0061

miR-196-1 prec (186)

0.0053

-0.0053

miR-10a (30)

0.0049

-0.0049

miR-99b prec (88)

0.0045

-0.0045

miR-196-1 (185)

0.0044

-0.0044

miR-199b (194)

0.0039

-0.0039

miR-191 (177)

0.0032

-0.0032

miR-195 (184)

7.00E-04

-7.00E-04

miR-155 (157)

7.00E-04

-7.00E-04

Thirty-eight miRs selected, misclassification error after cross validation of 0.31. Thirty-five overexpressed miRs in cancer are indicated by positive cancer scores; three down-regulated miRs are indicated by negative cancer scores.





Table 8. MicroRNAs selected by prediction analysis of microarray (PAM) in pancreas (cancer vs. normal tissues)

miRNA (ID)

Pancreas cancer score

Pancreas normal score

miR-103-2 (96)

0.4746

-1.582

miR-103-1 (97)

0.4089

-1.3631

miR-24-2 (54)

0.4059

-1.3529

miR-107 (100)

0.3701

-1.2336

miR-100 (91)

0.3546

-1.182

miR-125b-2 (111)

0.3147

-1.0489

miR-125b-1 (109)

0.3071

-1.0237

miR-24-1 (52)

0.2846

-0.9488

miR-191 (177)

0.2661

-0.887

miR-23a (50)

0.2586

-0.8619

miR-26a-1 (56)

0.2081

-0.6937

miR-125a (107)

0.1932

-0.644

miR-130a (120)

0.1891

-0.6303

miR-26b (58)

0.1861

-0.6203

miR-145 (143)

0.1847

-0.6158

miR-221 (224)

0.177

-0.59

miR-126* (102)

0.1732

-0.5772

miR-16-2 (39)

0.1698

-0.5659

miR-146 (144)

0.1656

-0.552

miR-214 (212)

0.1642

-0.5472

miR-99b (89)

0.1636

-0.5454

miR-128b (115)

0.1536

-0.512

miR-155 (157)

-0.1529

0.5098

miR-29b-2 (95)

0.1487

-0.4956

miR-29a (62)

0.1454

-0.4848

miR-25 (55)

0.1432

-0.4775

miR-16-1 (38)

0.1424

-0.4746

miR-99a (90)

0.1374

-0.4581

miR-224 (228)

0.1365

-0.4549

miR-30d (72)

0.1301

-0.4336

miR-92-2 (82)

0.116

-0.3865

miR-199a-1 (191)

0.1158

-0.3861

miR-223 (227)

0.1141

-0.3803

miR-29c (65)

0.113

-0.3768

miR-30b (68)

0.1008

-0.3361

miR-129-1/2 (117)

0.1001

-0.3337

miR-197 (189)

0.0975

-0.325

miR-17-5p (41)

0.0955

-0.3185

miR-30c (70)

0.0948

-0.316

miR-7-1 (19)

0.0933

-0.311

miR-93-1 (83)

0.0918

-0.3061

miR-140 (136)

0.0904

-0.3015

miR-30a-5p (66)

0.077

-0.2568

miR-132 (121)

0.0654

-0.2179

miR-181b-1 (210)

0.0576

-0.1918

miR-152 prec (151)

-0.0477

0.1591

miR-23b (51)

0.0469

-0.1562

miR-20a (46)

0.0452

-0.1507

miR-222 (225)

0.0416

-0.1385

miR-27a (59)

0.0405

-0.1351

miR-92-1 (81)

0.0332

-0.1106

miR-21 (47)

0.0288

-0.0959

miR-129-1/2 prec (118)

0.0282

-0.0939

miR-150 (148)

0.0173

-0.0578

miR-32 (75)

0.0167

-0.0558

miR-106a (99)

0.0142

-0.0473

miR-29b-1 (64)

0.0084

-0.028

Fifty-seven miRs selected, misclassification error after cross validation of 0.02. Fifty-five overexpressed miRs in cancer are indicated by positive cancer scores; two down-regulated miRs are indicated by negative cancer scores.





Table 9. MicroRNAs selected by prediction analysis of microarray (PAM) in prostate (cancer vs. normal tissues)

miRNA (ID)

Prostate cancer score

Prostate normal score

let-7d (8)

0.0528

-0.4227

miR-128a prec (113)

-0.0412

0.3298

miR-195 (184)

0.04

-0.3199

miR-203 (197)

0.0356

-0.2851

let-7a-2 prec (2)

-0.0313

0.2504

miR-34a (78)

0.0303

-0.2428

miR-20a (46)

0.029

-0.2319

miR-218-2 (221)

-0.0252

0.2018

miR-29a (62)

0.0247

-0.1978

miR-25 (55)

0.0233

-0.1861

miR-95 (84)

0.0233

-0.1861

miR-197 (189)

0.0198

-0.1587

miR-135-2 (128)

0.0198

-0.1582

miR-187 (173)

0.0192

-0.1535

miR-196-1 (185)

0.0176

-0.1411

miR-148 (146)

0.0175

-0.1401

miR-191 (177)

0.017

-0.136

miR-21 (47)

0.0169

-0.1351

let-7i (10)

0.0163

-0.1303

miR-198 (190)

0.0145

-0.1161

miR-199a-2 (192)

0.0136

-0.1088

miR-30c (70)

0.0133

-0.1062

miR-17-5p (41)

0.0132

-0.1053

miR-92-2 (82)

0.012

-0.0961

miR-146 (144)

0.0113

-0.0908

miR-181b-1 prec (211)

0.011

-0.0878

miR-32 (75)

0.0109

-0.0873

miR-206 (202)

0.0104

-0.083

miR-184 prec (169)

0.0096

-0.0764

miR-29a prec (63)

-0.0095

0.076

miR-29b-2 (95)

0.0092

-0.0739

miR-149 (147)

-0.0084

0.0676

miR-181b-1 (210)

0.0049

-0.0392

miR-196-1 prec (186)

0.0042

-0.0335

miR-93-1 (83)

0.0039

-0.0312

miR-223 (227)

0.0038

-0.0308

miR-16-1 (38)

0.0028

-0.0226

miR-101-1 prec (92)

0.0015

-0.0123

miR-124a-1 (104)

0.0015

-0.0119

miR-26a-1 (56)

0.0015

-0.0119

miR-214 (212)

0.0013

-0.0105

miR-27a (59)

0.0011

-0.0091

miR-24-1 (53)

-8.00E-04

0.0067

miR-106a (99)

7.00E-04

-0.0057

miR-199a-1 (191)

4.00E-04

-0.0029

T

= 1, 45 miRs selected, misclassification error after cross validation of 0.11. Thirty-nine overexpressed miRs in cancer are indicated by positive cancer scores; six down-regulated miRs are indicated by negative cancer scores.





Table 10. MicroRNAs selected by prediction analysis of microarray (PAM) in stomach (cancer vs. normal tissues)

miRNA (ID)

Stomach cancer score

Stomach normal score

miR-223 (227)

0.1896

-0.1806

miR-21 (47)

0.1872

-0.1783

miR-218-2 (221)

-0.1552

0.1478

miR-103-2 (96)

0.1206

-0.1148

miR-92-2 (82)

0.1142

-0.1088

miR-25 (55)

0.1097

-0.1045

miR-136 (130)

-0.1097

0.1045

miR-191 (177)

0.0946

-0.0901

miR-221 (224)

0.0919

-0.0876

miR-125b-2 (111)

0.0913

-0.0869

miR-103-1 (97)

0.0837

-0.0797

miR-214 (212)

0.0749

-0.0713

miR-222 (225)

0.0749

-0.0713

miR-212 prec (209)

-0.054

0.0514

miR-125b-1 (109)

0.0528

-0.0503

miR-100 (91)

0.0526

-0.0501

miR-107 (100)

0.0388

-0.0369

miR-92-1 (81)

0.0369

-0.0351

miR-96 (86)

-0.0306

0.0291

miR-192 (178)

0.0236

-0.0224

miR-23a (50)

0.022

-0.021

miR-215 (213)

0.0204

-0.0194

miR-7-2 (21)

0.0189

-0.018

miR-138-2 (133)

-0.0185

0.0176

miR-24-1 (52)

0.0151

-0.0144

miR-99b (89)

0.0098

-0.0093

miR-33b (76)

-0.0049

0.0046

miR-24-2 (54)

0.0041

-0.0039

T =

1, 28 miRs selected, misclassification error after cross validation of 0.19. Twenty-two overexpressed miRs in cancer are indicated by positive cancer scores; six down-regulated miRs are indicated by negative cancer scores.





Table 11. Differentially regulated miRs in all six solid cancer types vs. normal tissues (T statistics): Two-class comparison

miRNA

ID

Cancer mean

Normal mean

Test stat

Raw P

Adjusted P

miR-21

47

11.538663

9.648338

7.861136

2.00E-06

2.00E-06

miR-141

137

9.024091

7.905398

6.238014

2.00E-06

2.00E-06

miR-212

208

13.540651

14.33617

-6.57942

2.00E-06

2.00E-06

miR-128a prec

113

12.32588

13.522675

-6.76388

2.00E-06

2.00E-06

miR-138-2

133

11.739557

13.144746

-7.01204

2.00E-06

2.00E-06

miR-218-2

221

11.279787

12.539366

-7.40557

2.00E-06

2.00E-06

miR-23b

51

14.169748

15.949736

-8.37744

2.00E-06

2.00E-06

miR-195

184

10.343991

9.172985

5.763262

2.00E-06

1.00E-05

miR-212 prec

209

12.686966

13.661763

-5.83132

4.00E-06

1.00E-05

miR-29b-2

95

11.27556

9.940731

5.660854

2.00E-06

1.40E-05

miR-199a-1

191

10.032008

8.920183

5.528849

2.00E-06

3.00E-05

miR-9-3

28

11.461922

12.570412

-5.43006

2.00E-06

4.60E-05

miR-128a

114

13.024235

13.856624

-5.35102

6.00E-06

7.20E-05

let-7a-1

1

12.616569

13.455246

-5.35346

2.00E-06

7.20E-05

let-7b

5

13.42636

14.068521

-5.17701

1.00E-05

0.000146

miR-16-2

39

10.460707

9.305895

5.048375

4.00E-06

0.000224

miR-199a-2

192

9.714225

8.759237

4.862553

1.00E-05

0.000494

miR-152 prec

151

11.388676

12.357529

-4.83716

2.00E-06

0.00053

miR-16-1

38

10.443169

9.338182

4.755258

1.00E-05

0.00071

miR-30d

72

13.982017

14.775206

-4.5707

1.20E-05

0.001476

miR-34a

78

10.675566

9.63769

4.467301

2.60E-05

0.00217

miR-17-5p

41

11.567244

10.281468

4.341834

3.80E-05

0.0034

miR-128b

115

10.930395

9.947746

4.304764

3.80E-05

0.003912

miR-20a

46

11.409852

10.19284

4.304678

3.20E-05

0.003912

miR-181b-1 prec

211

9.577504

8.804294

4.285968

4.80E-05

0.004126

miR-132

121

9.599947

8.775966

4.284737

5.60E-05

0.004126

miR-200b

195

9.475221

8.527243

4.221511

4.00E-05

0.0052

let-7a-3

4

10.436089

9.511546

4.08952

0.000104

0.008242

miR-138-1

132

8.299613

9.200253

-4.05204

5.60E-05

0.00931

miR-29c

65

11.291005

10.326912

4.019385

0.000144

0.010312

miR-29a

62

11.381359

10.461075

4.013697

0.00015

0.010398

miR-96

86

11.37218

12.136636

-3.94825

0.000138

0.012962

miR-191

177

13.498207

12.729872

3.817228

0.000158

0.02015

miR-27a

59

10.399338

9.548582

3.715048

0.000344

0.028096

let-7g

15

10.819688

10.01157

3.653239

0.000426

0.033874

miR-9-1

24

10.102819

9.212988

3.651886

0.000388

0.033874

miR-125a

107

10.960998

10.005312

3.651356

0.000452

0.033874

miR-95

84

9.435733

8.751331

3.59406

0.000478

0.039594

miR-155

157

12.505359

13.231221

-3.58369

0.000614

0.040394

miR-199b

194

9.755066

9.082751

3.55934

0.000588

0.04314

miR-24-2

54

12.611696

11.612557

3.518774

0.00087

0.048278

let-7e

11

12.497795

13.055093

-3.51589

0.00054

0.048354

miR-92-1

81

16.081074

16.592426

-3.50446

0.000928

0.049828

Forty-three miRs have an adjusted P value lower than 0.05. Twenty-six miRs are overexpressed and 17 underregulated in breast, colon, lung, pancreas, prostate, and stomach carcinomas when compared with the normal tissues





Table 12. Differentially regulated miRs in six solid cancer types vs. normal tissues (SAM, significance analysis of microarrays)

miRNA

ID

d

value

SD

P

value

q

value

R

fold

miR-21

#47

3.156

0.24

0

0

2.593

miR-23b

#51

-3.117

0.212

0

0

0.443

miR-138-2

#133

-2.514

0.2

0

0

0.402

miR-218-2

#221

-2.383

0.17

0

0

0.384

miR-29b-2

#95

2.246

0.236

0

0

1.868

miR-128a prec

#113

-2.235

0.177

0

0

0.368

miR-195

#184

2.085

0.203

0

0

1.695

miR-141

#137

2.08

0.179

0

0

2.459

miR-199a-1

#191

1.987

0.201

0

0

1.945

miR-9-3

#28

-1.97

0.204

0

0

0.433

miR-16-2

#39

1.966

0.229

0

0

1.788

miR-17-5p

#41

1.964

0.296

0

0

0.725

miR-20a

#46

1.898

0.283

0

0

0.969

miR-16-1

#38

1.87

0.232

0

0

1.447

miR-212 prec

#209

-1.854

0.167

0

0

0.509

miR-34a

#78

1.756

0.232

0

0

1.219

miR-152 prec

#151

-1.734

0.2

0

0

0.46

miR-199a-2

#192

1.721

0.196

0

0

1.838

miR-128b

#115

1.674

0.228

0

0

1.266

miR-212

#208

-1.659

0.121

0

0

0.627

let-7a-1

#1

-1.628

0.157

0

0

0.461

miR-200b

#195

1.626

0.225

0

0

1.432

miR-128a

#114

-1.619

0.156

0

0

0.511

miR-29c

#65

1.611

0.24

0

0

1.225

let-7a-3

#4

1.581

0.226

0

0

1.109

miR-29a

#62

1.565

0.229

0

0

1.706

miR-24-2

#54

1.555

0.284

0

0

0.831

miR-138-1

#132

-1.551

0.222

0

0

0.432

miR-125a

#107

1.541

0.262

0

0

1.164

miR-106a

#99

1.514

0.275

0

0

0.952

miR-132

#121

1.496

0.192

0

0

2.158

miR-30d

#72

-1.491

0.174

0

0

0.424

miR-9-1

#24

1.478

0.244

0

0

0.763

miR-27a

#59

1.448

0.229

0

0

1.174

miR-181b-1 prec

#211

1.435

0.18

0

0

1.525

let-7g

#15

1.394

0.221

0

0

1.072

miR-96

#86

-1.384

0.194

0

0

0.519

miR-191

#177

1.372

0.201

0

0

1.165

miR-93-1

#83

1.363

0.266

0

0

0.775

miR-136

#130

-1.355

0.267

0

0

0.364

miR-205

#201

1.343

0.309

0

0

1.281

miR-185

#170

1.287

0.222

0.001

0.001

0.609

miR-125b-1

#109

1.262

0.283

0.001

0.001

1.215

miR-10a

#30

1.252

0.227

0.001

0.001

1.643

miR-95

#84

1.247

0.19

0.001

0.001

1.509

miR-199b

#194

1.228

0.189

0.001

0.001

1.246

miR-10b

#32

1.219

0.232

0.002

0.001

1.342

let-7i

#10

1.216

0.203

0.002

0.001

1.026

miR-210

#205

1.213

0.237

0.002

0.001

1.088

Thirty-five miRs are overexpressed and 14 are underregulated in breast, colon, lung, pancreas, prostate, and stomach carcinomas (Delta = 0.9, false discovery rate = 0.001).





Table 13. MicroRNAs selected by PAM (prediction analysis of microarray) in six solid cancer types vs. normal tissues

miRNA

ID

Solid cancer score

Normal tissues score

miR-21

47

0.0801

-0.2643

miR-138-2

133

-0.055

0.1815

miR-218-2

221

-0.0535

0.1765

miR-23b

51

-0.0516

0.17

miR-128a prec

113

-0.0498

0.1642

miR-29b-2

95

0.0457

-0.1508

miR-195

184

0.0404

-0.1333

miR-17-5p

41

0.0383

-0.1263

miR-9-3

28

-0.0357

0.1176

miR-212 prec

209

-0.0342

0.1129

miR-20a

46

0.0322

-0.1061

miR-141

137

0.0322

-0.1061

miR-199a-1

191

0.0319

-0.1053

miR-16-2

39

0.0315

-0.1037

miR-152 prec

151

-0.0283

0.0933

miR-16-1

38

0.0277

-0.0913

miR-34a

78

0.0269

-0.0886

miR-212

208

-0.0265

0.0875

let-7a-1

1

-0.0264

0.0872

miR-128a

114

-0.0259

0.0855

miR-128b

115

0.0254

-0.0839

miR-24-2

54

0.0244

-0.0803

miR-29c

65

0.0224

-0.0738

miR-199a-2

192

0.0223

-0.0736

let-7a-3

4

0.0221

-0.073

miR-191

177

0.0188

-0.062

miR-125a

107

0.0186

-0.0613

miR-30d

72

-0.0185

0.061

miR-29a

62

0.0184

-0.0608

miR-106a

99

0.0177

-0.0584

miR-93-1

83

0.0163

-0.0537

miR-200b

195

0.0159

-0.0524

let-7g

15

0.0158

-0.0521

miR-27a

59

0.0157

-0.0518

miR-96

86

-0.0156

0.0514

let-7b

5

-0.0152

0.0501

miR-138-1

132

-0.0151

0.0499

miR-9-1

24

0.0136

-0.0448

miR-181b-1 prec

211

0.0134

-0.0442

miR-155

157

-0.0128

0.0423

miR-132

121

0.0127

-0.0418

miR-136

130

-0.0112

0.037

let-7i

10

0.0103

-0.034

miR-210

205

0.0074

-0.0245

miR-205

201

0.0073

-0.024

miR-185

170

0.0071

-0.0234

miR-24-1

52

0.007

-0.023

miR-199b

194

0.0064

-0.021

miR-125b-1

109

0.006

-0.0199

miR-206 prec

203

-0.005

0.0166

miR-10a

30

0.0045

-0.015

miR-95

84

0.0045

-0.0149

let-7e

11

-0.0039

0.013

miR-124a-3

106

-0.0028

0.0091

miR-10b

32

0.002

-0.0066

miR-185 prec

171

-0.0014

0.0047

miR-92-1

81

-2.00E-04

5.00E-04

T

= 1.5 and misclassification error = 0.176. Thirty-six overexpressed miRs in cancer are indicated by positive cancer scores; 21 down-regulated miRs are indicated by negative cancer scores.





Table 14. Oncogenes and tumor suppressor genes predicted by TargetScanS as targets of microRNAs from the described microRNA cancer subset*

miRNA gene

Gene name

Gene description

miR-26a, miR-146 

ABL2

v-abl Abelson murine leukemia viral oncogene homolog 2 (arg, Abelson-related gene)

 miR-107

AF5q31

ALL1 fused gene from 5q31

miR-20, miR-125b 

AKT3

v-akt murine thymoma viral oncogene homolog 3

miR-26a, miR-155 miR-125b

APC

adenomatosis polyposis coli

miR-26a, miR-218 

ARHGEF12

RHO guanine nucleotide exchange factor (GEF) 12 (LARG)

 miR-107, miR-221

ARNT

aryl hydrocarbon receptor nuclear translocator

 miR-192

ATF1

activating transcription factor 1

 miR-26a

ATM

Ataxia telangiectasia mutated (includes complementation groups A, C and D)

 miR-24

AXL

AXL receptor tyrosine kinase

 miR-26a, miR-107, miR-146, miR-155 miR-138, miR-92

BCL11A

B-cell CLL/lymphoma 11A

 miR-20

BCL11B

B-cell CLL/lymphoma 11B (CTIP2)

 miR-21

BCL2

B-cell CLL/lymphoma 2

miR-26a,  miR-26a miR-20,

BCL6

B-cell CLL/lymphoma 6 (zinc finger protein 51)

 miR-92

BCL9

B-cell CLL/lymphoma 9

 miR-26a, miR-223 miR-221, miR-125b

CBFB

core-binding factor, beta subunit

 miR-218

CCDC6

coiled-coil domain containing 6

 miR-20

CCND1

cyclin D1 (PRAD1: parathyroid adenomatosis 1)

 miR-26a, miR-20

CCND2

cyclin D2

 miR-26a, miR-107, miR-92

CDK6

cyclin-dependent kinase 6

 miR-20

CDKN1A

cyclin-dependent kinase inhibitor 1A (p21, Cip1)

 miR-221, miR-92

CDKN1C

cyclin-dependent kinase inhibitor 1C (p57, Kip2)

 miR-24

CDX2

caudal type homeo box transcription factor 2

 miR-92

CEBPA

CCAAT/enhancer binding protein (C/EBP), alpha

miR-26a 

CLTC

clathrin, heavy polypeptide (Hc)

 miR-218

COL1A1

collagen, type I, alpha 1

 miR-26a

CREBBP

CREB binding protein (CBP)

miR-20 

CRK

v-crk avian sarcoma virus CT10 oncogene homolog

 miR-20

CSF1

colony stimulating factor 1 (macrophage)

 miR-221, miR-192

DDX6

DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 6 (RNA helicase, 54kD)

 miR-138

DEK

DEK oncogene (DNA binding)

 miR-20

E2F1

E2F transcription factor 1

 miR-20

ELK3

ELK3, ETS-domain protein (SRF accessory protein 2)

 miR-24

ELL

ELL gene (11-19 lysine-rich leukemia gene)

miR-26a, miR-138 

ERBB4

v-erb-a avian erythroblastic leukemia viral oncogene homolog-like 4

miR-221, miR-155, miR-125b 

ETS1

v-ets avian erythroblastosis virus E26 oncogene homolog 1

 miR-20

ETV1

ets variant gene 1

 miR-125b

ETV6

ets variant gene 6 (TEL oncogene)

 miR-223

FAT

FAT tumor suppressor (Drosophila) homolog

 miR-223, miR-125b, miR-218

FGFR2

fibroblast growth factor receptor 2

miR-92 

FLI1

Friend leukemia virus integration 1

 miR-24, miR-20

FLT1

fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)

miR-221 

FOS

v-fos FBJ murine osteosarcoma viral oncogene homolog

 miR-92

FOXG1B

forkhead box G1B

 miR-223

FOXO3A

forkhead box O3A

 miR-125b

GOLGA5

golgi autoantigen, golgin subfamily a, 5 (PTC5)

 miR-138

GPHN

gephyrin (GPH)

 miR-107, miR-223, miR-20, miR-218

HLF

hepatic leukemia factor

 miR-26a, miR-107

HMGA1

high mobility group AT-hook 1

 miR-20

HOXA13

homeo box A13

 miR-92

HOXA9

homeo box A9

 miR-125b

IRF4

interferon regulatory factor 4

 miR-146, miR-20, miR-138

JAZF1

juxtaposed with another zinc finger gene 1

miR-92

JUN

v-jun avian sarcoma virus 17 oncogene homolog

miR-155  

KRAS

v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog

 miR-218

LASP1

LIM and SH3 protein 1

 miR-218

LHFP

lipoma HMGIC fusion partner

 miR-125b, miR-218

LIFR

leukemia inhibitory factor receptor

 miR-223

LMO2

LIM domain only 2 (rhombotin-like 1) (RBTN2)

miR-223, miR-155, miR-125b, miR-92 

MAF

v-maf musculoaponeurotic fibrosarcoma (avian) oncogene homolog

 miR-92

MAP2K4

mitogen-activated protein kinase kinase 4

 miR-146, miR-20

MAP3K8

mitogen-activated protein kinase kinase kinase 8

 miR-125b

MAX

MAX protein

 miR-218

MCC

mutated in colorectal cancers

 miR-24

MEN1

multiple endocrine neoplasia I

 miR-138

MLLT6

myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 6 (AF17)

 miR-192

MSN

moesin

miR-24 

MYB

v-myb avian myeloblastosis viral oncogene homolog

miR-107, miR-223, miR-146, miR-221, miR-155, miR-218 

MYBL1

v-myb avian myeloblastosis viral oncogene homolog-like 1

miR-107, miR-20 

MYCN

v-myc avian myelocytomatosis viral related oncogene, neuroblastoma derived

miR-107,  miR-92

MYH9

myosin, heavy polypeptide 9, non-muscle

 miR-24

MYST4

MYST histone acetyltransferase (monocytic leukemia) 4 (MORF)

miR-20

NBL1

neuroblastoma, suppression of tumorigenicity 1

miR-125b

NIN

ninein (GSK3B interacting protein)

miR-26a, miR-107

NKTR

natural killer-tumor recognition sequence

miR-92 

NOTCH1

Notch homolog 1, translocation-associated (Drosophila) (TAN1)

miR-24

NTRK3

neurotrophic tyrosine kinase, receptor, type 3

miR-125b 

PCSK7

proprotein convertase subtilisin/kexin type 7

miR-24, miR-146 

PER1

period homolog 1 (Drosophila)

miR-146, miR-125b, miR-138,

PHOX2B

paired-like homeobox 2b

miR-155 

PICALM

phosphatidylinositol binding clathrin assembly protein (CALM)

miR-24, miR-26a

PIM1

pim-1 oncogene

miR-24, miR-26a, miR-21, miR-107, miR-20, miR-155 

PLAG1

pleiomorphic adenoma gene 1

miR-218 

RAB8A

RAB8A, member RAS oncogene family

miR-24, miR-221 

RALA

v-ral simian leukemia viral oncogene homolog A (ras related)

miR-138 

RARA

retinoic acid receptor, alpha

miR-20, miR-106,miR-192

RB1

retinoblastoma 1 (including osteosarcoma)

miR-20,  

RBL1

retinoblastoma-like 1 (p107)

miR-20 

RBL2

retinoblastoma-like 2 (p130)

miR-155, miR-138 

REL

v-rel avian reticuloendotheliosis viral oncogene homolog

miR-20, miR-138 

RHOC

ras homolog gene family, member C

miR-20, miR-192 

RUNX1

runt-related transcription factor 1 (AML1)

miR-107, miR-223 

SEPT6

septin 6

miR-146, miR-20, miR-125b 

SET

SET translocation

miR-21, miR-20, miR-155, miR-218 

SKI

v-ski avian sarcoma viral oncogene homolog

miR-26a, miR-146 

SMAD4

SMAD, mothers against DPP homolog 4 (Drosophila)

miR-155 

SPI1

spleen focus forming virus (SFFV) proviral integration oncogene spi1

miR-125b 

SS18

synovial sarcoma translocation, chromosome 18

miR-107, miR-155 

SUFU

suppressor of fused homolog (Drosophila)

miR-92 

TAF15

TAF15 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 68kDa

miR-26a, miR-221, miR-138 

TCF12

transcription factor 12 (HTF4, helix-loop-helix transcription factors 4)

miR-21, miR-20 

TGFBR2

transforming growth factor, beta receptor II (70-80kD)

miR-24, miR-26a, miR-92 

TOP1

topoisomerase (DNA) I

miR-138 

TPM4

tropomyosin 4

miR-20 

TRIP11

thyroid hormone receptor interactor 11

miR-92 

TSC1

Tuberous sclerosis 1

miR-20 

TSG101

Tumor susceptibility gene 101

miR-20 

TUSC2

Tumor suppressor candidate 2 

miR-24 

VAV1

vav 1 oncogene

miR-125b 

VAV2

vav 2 oncogene

miR-107 

WHSC1

Wolf-Hirschhorn syndrome candidate 1(MMSET)

miR-138 

WHSC1L1

Wolf-Hirschhorn syndrome candidate 1-like 1 (NSD3)

miR-26a 

WNT5A

wingless-type MMTV integration site family, member 5A

miR-26a, miR-20, miR-125b 

YES1

v-yes-1 Yamaguchi sarcoma viral oncogene homolog 1

miR-107, miR-221 

ZNF198

zinc finger protein 198

miR-218 

ZNFN1A1

zinc finger protein, subfamily 1A, 1 (Ikaros)

*Known cancer genes list (tumor suppressors and oncogenes) was as identified in the Cancer Gene Census at www.sanger.ac.uk/genetics/CGP/Census/ or reported by OMIM at www.ncbi.nlm.nih.gov.