Details of Host Protein-DME Interaction (HOSPPI)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0113)
DME Name	Heparanase (HPSE), Homo sapiens	DME Info
UniProt ID	HPSE_HUMAN
EC Number	EC: 3.2.1.166 (Click to Show/Hide the Complete EC Tree) Hydrolases Glycosylase O/S-glycosyl compound glycosidase EC: 3.2.1.166
Lineage	Species: Homo sapiens (Click to Show/Hide the Complete Species Lineage) Kingdom: Metazoa Phylum: Chordata Class: Mammalia Order: Primates Family: Hominidae Genus: Homo Species: Homo sapiens
Interactome

Disease Specific Interactions between Host Protein and DME (HOSPPI)
ICD Disease Classification 02 Neoplasms
ICD-11: 2B71 Gastric cancer		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
Non-coding RNA regulation
hsa-miR-558		Gastric cancer		Suppression
miRBase ID	MIMAT0003222
Interaction Name	hsa-miR-558--HPSE regulation				[1]
Studied Cell Lines	AGS, SGC-7901, MKN-28 and MKN-45 cell lines
Description	hsa-miR-558 is reported to suppress HPSE mRNA translation by binding to the 3' untranslated region (3'UTR) of HPSE mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Heparanase.
ICD-11: 2B90 Colorectal cancer		Click to Show/Hide the Full List of HOSPPI: 2 HOSPPI
Transcription-factor regulation
Nuclear factor kappa-B p105 (NFKB1)		Colorectal cancer		Activation
Uniprot ID	NFKB1_HUMAN
Interaction Name	NFKB1-HPSE interaction				[2], [3]
Studied Cell Lines	LS-174T cell line
Ensembl ID	ENSG00000109320
Description	Nuclear factor kappa-B p105 (NFKB1) is reported to activate the transcription of HPSE gene, which leads to an increased expression of the drug-metabolizing enzyme Heparanase. As a result, the interaction between NFKB1 and HPSE can activate the drug-metabolizing process of Heparanase.
Transcription factor p65 (RELA)		Colorectal cancer		Activation
Uniprot ID	TF65_HUMAN
Interaction Name	RELA-HPSE interaction				[2], [3]
Studied Cell Lines	LS-174T cell line
Ensembl ID	ENSG00000173039
Description	Transcription factor p65 (RELA) is reported to activate the transcription of HPSE gene, which leads to an increased expression of the drug-metabolizing enzyme Heparanase. As a result, the interaction between RELA and HPSE can activate the drug-metabolizing process of Heparanase.
ICD-11: 2C12 Liver cancer		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
DNA methylation
DNA methyltransferase (DNMT)		Liver cancer		Moderate hypomethylation
Interaction Name	DNMT-HPSE interaction
The Methylation Level of Disease Section Compare with the Healthy Individual Tissue	Moderate hypomethylation p-value: 2.14E-03; delta-beta: -2.52E-01
Description	DNA methyltransferase (DNMT) is reported to moderatly hypo-methylate the HPSE gene, which leads to a moderatly increased expression of the drug-metabolizing enzyme Heparanase. As a result, the interaction between DNMT and HPSE can moderatly affect the drug-metabolizing process of Heparanase.
The Methylation Level of Disease Section Compare with the Adjacent Tissue	Moderate hypomethylation p-value: 4.66E-09; delta-beta: -2.57E-01
Description	DNA methyltransferase (DNMT) is reported to moderatly hypo-methylate the HPSE gene, which leads to a moderatly increased expression of the drug-metabolizing enzyme Heparanase. As a result, the interaction between DNMT and HPSE can moderatly affect the drug-metabolizing process of Heparanase.
The Methylation Level of Disease Section Compare with the Other Disease Section	Moderate hypomethylation p-value: 2.34E-06; delta-beta: -2.43E-01
Description	DNA methyltransferase (DNMT) is reported to moderatly hypo-methylate the HPSE gene, which leads to a moderatly increased expression of the drug-metabolizing enzyme Heparanase. As a result, the interaction between DNMT and HPSE can moderatly affect the drug-metabolizing process of Heparanase.
DME methylation in the diseased tissue of patients DME methylation in the normal tissue adjacent to the diseased tissue of patients DME methylation in the normal tissue of healthy individuals DME methylation in tissue other than the diseased tissue of patients
Violin Diagram of DME Disease-specific Methylation Level			Click to View the Clearer Original Diagram
Download DME methylation barchart for all samples Download DME methylation data of patients in the disease section of the tissue Download DME methylation data of patients in the normal section of the tissue adjacent to the disease section Download DME methylation data in the tissue of healthy individual Download DME methylation data in the tissue of the other disease section
ICD-11: 2C60 Breast cancer		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
Non-coding RNA regulation
hsa-miR-1258		Breast cancer		Suppression
miRBase ID	MIMAT0005909
Interaction Name	hsa-miR-1258--HPSE regulation				[4]
Studied Cell Lines	MDA-MB-231 cell line
Description	hsa-miR-1258 is reported to suppress HPSE mRNA translation by binding to the 3' untranslated region (3'UTR) of HPSE mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Heparanase.
ICD-11: 2C82 Prostate cancer		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
Transcription-factor regulation
Early growth response 1 (EGR1)		Prostate cancer		Activation
Uniprot ID	EGR1_HUMAN
Interaction Name	EGR1-HPSE interaction				[5], [6]
Studied Cell Lines	Du145, DuPro, LNCaP and PC-3 cell lines
Ensembl ID	ENSG00000120738
Description	Early growth response 1 (EGR1) is reported to activate the transcription of HPSE gene, which leads to an increased expression of the drug-metabolizing enzyme Heparanase. As a result, the interaction between EGR1 and HPSE can activate the drug-metabolizing process of Heparanase.
ICD-11: 2D50 Brain cancer metastasis		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
DNA methylation
DNA methyltransferase (DNMT)		Esthesioneuroblastoma		Significant hypomethylation
Interaction Name	DNMT-HPSE interaction
The Methylation Level of Disease Section Compare with the Healthy Individual Tissue	Significant hypomethylation p-value: 2.48E-12; delta-beta: -3.11E-01
Description	DNA methyltransferase (DNMT) is reported to significantly hypo-methylate the HPSE gene, which leads to a significantly increased expression of the drug-metabolizing enzyme Heparanase. As a result, the interaction between DNMT and HPSE can significantly affect the drug-metabolizing process of Heparanase.
DME methylation in the diseased tissue of patients DME methylation in the normal tissue of healthy individuals
Violin Diagram of DME Disease-specific Methylation Level			Click to View the Clearer Original Diagram
Download DME methylation barchart for all samples Download DME methylation data of patients in the disease section of the tissue Download DME methylation data in the tissue of healthy individual

References
1	miRNA-558 promotes gastric cancer progression through attenuating Smad4-mediated repression of heparanase expression. Cell Death Dis. 2016 Sep 29;7(9):e2382.
2	Role of eukaryotic initiation factor-4E (eIF-4E) in regulation of expression of NF-kappaB and its subsequent influence on transcription and activity of heparanase in human colon adenocarcinoma cell line. Ai Zheng. 2003 Oct;22(10):1023-9.
3	Expression of heparanase and nuclear factor kappa B in pancreatic adenocarcinoma. Nan Fang Yi Ke Da Xue Xue Bao. 2007 Aug;27(8):1267-70.
4	MicroRNA-1258 suppresses breast cancer brain metastasis by targeting heparanase. Cancer Res. 2011 Feb 1;71(3):645-54.
5	Increased heparanase expression is caused by promoter hypomethylation and up-regulation of transcriptional factor early growth response-1 in human prostate cancer. Clin Cancer Res. 2005 Feb 1;11(3):1028-36.
6	Promoter CpG hypomethylation and transcription factor EGR1 hyperactivate heparanase expression in bladder cancer. Oncogene. 2005 Oct 13;24(45):6765-72.

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