DNA methylation, microRNAs, and their crosstalk as potential biomarkers in hepatocellular carcinoma

Table 3 Pathways and molecular functions regulated by methylation-silenced microRNA gene targets

No.	Panther	Genes	Gene	Contrib
GO molecular function1
1	Binding (GO:0005488)	2799	40.60%	33.80%
2	Catalytic activity (GO:0003824)	2126	30.80%	25.70%
3	Transcription regulator activity (GO:0030528)	920	13.30%	11.10%
4	Receptor activity (GO:0004872)	696	10.10%	8.40%
5	Structural molecule activity (GO:0005198)	558	8.10%	6.70%
6	Enzyme regulator activity (GO:0030234)	494	7.20%	6.00%
7	Transporter activity (GO:0005215)	418	6.10%	5.00%
8	Ion channel activity (GO:0005216)	152	2.20%	1.80%
9	Translation regulator activity (GO:0045182)	57	0.80%	0.70%
10	Motor activity (GO:0003774)	53	0.80%	0.60%
GO Biological process2
1	Metabolic process (GO:0008152)	3277	47.50%	20.80%
2	Cellular process (GO:0009987)	2564	37.20%	16.30%
3	Cell communication (GO:0007154)	1793	26.00%	11.40%
4	Developmental process (GO:0032502)	1315	19.10%	8.40%
5	Transport (GO:0006810)	1190	17.30%	7.60%
6	Immune system process (GO:0002376)	956	13.90%	6.10%
7	System process (GO:0003008)	927	13.40%	5.90%
8	Cell cycle (GO:0007049)	797	11.60%	5.10%
9	Cellular component organization (GO:0016043)	630	9.10%	4.00%
10	Response to stimulus (GO:0050896)	613	8.90%	3.90%
GO cellular component3
1	Intracellular (GO:0005622)	486	7.10%	50.40%
2	Extracellular region (GO:0005576)	233	3.40%	24.10%
3	Plasma membrane (GO:0005886)	86	1.20%	8.90%
4	Ribonucleoprotein complex (GO:0030529)	84	1.20%	8.70%
5	Protein complex (GO:0043234)	76	1.10%	7.90%
GO protein class4
1	Nucleic acid binding (PC00171)	1144	16.60%	12.60%
2	Transcription factor (PC00218)	920	13.30%	10.20%
3	Hydrolase (PC00121)	691	10.00%	7.60%
4	Receptor (PC00197)	690	10.00%	7.60%
5	Transferase (PC00220)	662	9.60%	7.30%
6	Enzyme modulator (PC00095)	634	9.20%	7.00%
7	Signaling molecule (PC00207)	481	7.00%	5.30%
8	Transporter (PC00227)	457	6.60%	5.00%
9	Cytoskeletal protein (PC00085)	402	5.80%	4.40%
10	Kinase (PC00137)	316	4.60%	3.50%
Pathway5
1	Gonadotropin releasing hormone receptor pathway (P06664)	159	2.30%	4.80%
2	Wnt signaling pathway (P00057)	156	2.30%	4.70%
3	Inflammation mediated by chemokine and cytokine signaling pathway (P00031)	134	1.90%	4.00%
4	Integrin signalling pathway (P00034)	116	1.70%	3.50%
5	Angiogenesis (P00005)	98	1.40%	3.00%
6	EGF receptor signaling pathway (P00018)	84	1.20%	2.50%
7	Cadherin signaling pathway (P00012)	80	1.20%	2.40%
8	Huntington disease (P00029)	77	1.10%	2.30%
9	TGF-beta signaling pathway (P00052)	73	1.10%	2.20%
10	PDGF signaling pathway (P00047)	74	1.10%	2.20%
KEGG
hsa01100 metabolic pathways (434)
hsa05200 pathways in cancer (189)
hsa04151 PI3K-Akt signaling pathway (162)
hsa04010 MAPK signaling pathway (137)
hsa05205 proteoglycans in cancer (134)
hsa05166 HTLV-I infection (123)
hsa04510 Focal adhesion (116)
hsa04810 regulation of actin cytoskeleton (115)
hsa05202 transcriptional misregulation in cancer (100)
hsa04144 endocytosis (100)

¹Total genes n = 6893, total function hits n = 8282;

²Total genes n = 6893, total process hits n = 15740;

³Total genes n = 6893, total component hits n = 965;

⁴Total genes n = 6893, total protein classess n = 9050;

⁵Total genes n = 6893, total pathway hits n = 3313. Contrib: Contribution; PI3K: Phosphatidylinositol-3-kinase; MAPK: Mitogen-activated protein kinase; HTLV: Human T-lymphotropic virus 1; EGF: Epidermal growth factor; PDGF: Platelet-derived growth factor; TGF-β: Transforming growth factor beta.