Supplementary Information Differentially Expressed

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Supplementary Information

Differentially Expressed miRNAs in Hepatocellular Carcinoma Target Genes in the Genetic Information Processing and Metabolism Pathways

Thomas Thurnherr1, Way-Champ Mah2, Zhengdeng Lei3, Yu Jin1,2, Steven G. Rozen1,4 and Caroline G. Lee1,2,4,5,*

1

NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore,

Singapore 2

Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre

Singapore, Singapore 169610, Singapore 3

Program in Neuroscience and Behavioural Disorders, Duke-NUS Graduate Medical School, Singapore

4

Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School Singapore, Singapore

169547, Singapore 5

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore,

Singapore 119077, Singapore

* Corresponding author: Tel: +65-6436-8353; Email: [email protected]

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8.5 8.0 7.0

7.5

miR−93 (log scale)

9.0

9.5

Tumorous Non−tumorous

7

8

9

10

11

12

PTPRN2 (log scale)

Supplementary Figure S1 - Example of negative correlation: miR-93 and PTPRN2 Expression of miR-93 and PTPRN2 across tumorous and adjacent non-tumorous tissues are negatively correlated (Spearman’s rho=-0.53). The plot also illustrates that miR-93 is over-expressed (FC: 1.53; FDR: 2.16×10-16) and PTPRN2 is underexpressed (FC: 0.53; FDR: 1.89×10-21) in tumors.

Supplementary Figure S2 - GSEA enrichment plot Negatively correlated genes with miR-93 are over-represented in MirTarget2 predicted targets (FDR < 6.0×10-4)

Down-regulated miRNAs miR−26a 515

miR−122

192

30

247

50

155 97

333 miR−130a

miR−93

miR−21

186

50

Up-regulated miRNAs

49

557

148

302 0

miR−221

0

Supplementary Figure S3 - Common targets of differentially expressed miRNAs (GSEA core enrichment set)

Supplementary Figure S4 – Patients with high miR-130a expression in tumor show significantly better survival TCGA liver cancer data; log-rank test: p=0.003; cutoff: median miR-130a expression; Median TTD: median time-to-death in months (1st,3rd quartile; number of events).

Table&S1.&&Differentially&expressed&miRNAs&between& tumorous&(T)&and&adjacent&non@tumorous&tissues&(NT). T*vs.*NT miRNA Fold*change FDR miR2199a25p 24.51 2.07E224 miR2199a23p 22.78 7.22E218 miR214525p 22.39 2.32E214 miR22125p 2.29 1.33E217 miR2451a 22.19 1.20E208 miR2125b25p 22.13 5.08E217 miR222323p 21.92 2.76E218 miR299a25p 21.90 1.90E216 miR214323p 21.88 1.81E209 miR21469 1.80 6.11E209 miR248625p 21.77 1.27E221 miR212225p 21.67 1.50E205 miR2125a25p 21.65 1.83E211 miR2663a 1.64 9.85E206 miR2122423p 21.63 1.99E232 miR229625p 21.62 1.68E217 miR219525p 21.61 8.41E211 miR226a25p 21.60 7.71E210 miR21274a 1.59 9.26E214 miR2302b25p 21.59 4.01E248 miR2130a23p 21.55 1.14E212 miR222123p 1.55 2.55E210 miR21236 21.54 1.29E251 miR2302a25p 21.54 9.68E245 miR233a25p 21.54 6.15E245 miR29325p 1.53 2.16E216 miR218623p 21.53 1.13E240 miR2374b23p 21.53 6.15E245 miR215025p 21.51 2.42E209 miR2922 21.51 8.91E243 miR230a23p 21.51 1.13E238 miR2378a23p 21.51 2.77E210

Table4S2.44Correlation4between4shortlisted4miRNAs4across4tumor4and4adjacent4non$ tumorous4tissues

P%value

miR$21 miR$21 miR$93 miR$221 miR$26a miR$122 miR$130a

0.9686 0.0002 0.0024 %4