Details of Host Protein-DME Interaction (HOSPPI)

General Information of Drug-Metabolizing Enzyme (DME ID: DME0561)
DME Name	Matrix metalloproteinase-2 (MMP-2), Homo sapiens	DME Info
UniProt ID	MMP2_HUMAN
EC Number	EC: 3.4.24.24 (Click to Show/Hide the Complete EC Tree) Hydrolases Peptidase Metallopeptidase EC: 3.4.24.24
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 Healthy
ICD-11: Healthy		Click to Show/Hide the Full List of HOSPPI: 6 HOSPPI
Transcription-factor regulation
Activating TF factor 2 (ATF2)		Health		Activation
Uniprot ID	ATF2_HUMAN
Interaction Name	ATF2-MMP2 interaction				[1], [2]
Studied Cell Lines	MCF10A cell line
Ensembl ID	ENSG00000115966
Description	Activating TF factor 2 (ATF2) is reported to activate the transcription of MMP2 gene, which leads to an increased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between ATF2 and MMP2 can activate the drug-metabolizing process of Matrix metalloproteinase-2.
Nuclear receptor family 4 A1 (NR4A1)		Health		Activation
Uniprot ID	NR4A1_HUMAN
Interaction Name	NR4A1-MMP2 interaction				[6]
Studied Cell Lines	HTR-8/SVneo cell line
Ensembl ID	ENSG00000123358
Description	Nuclear receptor family 4 A1 (NR4A1) is reported to activate the transcription of MMP2 gene, which leads to an increased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between NR4A1 and MMP2 can activate the drug-metabolizing process of Matrix metalloproteinase-2.
Serum response factor (SRF)		Health		Activation
Uniprot ID	SRF_HUMAN
Interaction Name	SRF-MMP2 interaction				[7]
Studied Cell Lines	WI-38 and IMR-90 cell lines
Ensembl ID	ENSG00000112658
Description	Serum response factor (SRF) is reported to activate the transcription of MMP2 gene, which leads to an increased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between SRF and MMP2 can activate the drug-metabolizing process of Matrix metalloproteinase-2.
Non-coding RNA regulation
hsa-miR-125b-5p		Health		Suppression
miRBase ID	MIMAT0000423
Interaction Name	hsa-miR-125b-5p--MMP2 regulation				[3]
Studied Cell Lines	HaCaT cell line
Description	hsa-miR-125b-5p is reported to suppress MMP2 mRNA translation by binding to the 3' untranslated region (3'UTR) of MMP2 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2.
hsa-miR-29a-3p		Health		Suppression
miRBase ID	MIMAT0000086
Interaction Name	hsa-miR-29a-3p--MMP2 regulation				[4]
Studied Cell Lines	HEK293 cell line
Description	hsa-miR-29a-3p is reported to suppress MMP2 mRNA translation by binding to the 3' untranslated region (3'UTR) of MMP2 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2.
hsa-miR-520g-3p		Health		Suppression
miRBase ID	MIMAT0002858
Interaction Name	hsa-miR-520g-3p--MMP2 regulation				[5]
Studied Cell Lines	HTR-8/SVneo cell line
Description	hsa-miR-520g-3p is reported to suppress MMP2 mRNA translation by binding to the 3' untranslated region (3'UTR) of MMP2 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2.
ICD Disease Classification 02 Neoplasms
ICD-11: 2A00 Brain cancer		Click to Show/Hide the Full List of HOSPPI: 6 HOSPPI
Transcription-factor regulation
ARNT-interacting protein (HIF1A)		Glioblastoma		Repression
Uniprot ID	HIF1A_HUMAN
Interaction Name	HIF1A-MMP2 interaction				[8], [9]
Studied Cell Lines	U87MG, U251MG, U373MG and LN18 cell lines
Ensembl ID	ENSG00000100644
Description	ARNT-interacting protein (HIF1A) is reported to repress the transcription of MMP2 gene, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between HIF1A and MMP2 can repress the drug-metabolizing process of Matrix metalloproteinase-2.
Transcription factor Sp1 (SP1)		Glioblastoma		Activation
Uniprot ID	SP1_HUMAN
Interaction Name	SP1-MMP2 interaction				[12]
Studied Cell Lines	LN-18, LN-382, U87MG, U251MG, LN-444, SNB19, U118MG and LN-428 cell lines
Ensembl ID	ENSG00000185591
Description	Transcription factor Sp1 (SP1) is reported to activate the transcription of MMP2 gene, which leads to an increased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between SP1 and MMP2 can activate the drug-metabolizing process of Matrix metalloproteinase-2.
Twist-related 1 (TWIST1)		Glioblastoma		Activation
Uniprot ID	TWST1_HUMAN
Interaction Name	TWIST1-MMP2 interaction				[13]
Studied Cell Lines	T98G, SNB19, SF767 and U87MG cell lines
Ensembl ID	ENSG00000122691
Description	Twist-related 1 (TWIST1) is reported to activate the transcription of MMP2 gene, which leads to an increased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between TWIST1 and MMP2 can activate the drug-metabolizing process of Matrix metalloproteinase-2.
Twist-related 2 (TWIST2)		Glioblastoma		Activation
Uniprot ID	TWST2_HUMAN
Interaction Name	TWIST2-MMP2 interaction				[13]
Studied Cell Lines	T98G, SNB19, SF767 and U87MG cell lines
Ensembl ID	ENSG00000233608
Description	Twist-related 2 (TWIST2) is reported to activate the transcription of MMP2 gene, which leads to an increased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between TWIST2 and MMP2 can activate the drug-metabolizing process of Matrix metalloproteinase-2.
Non-coding RNA regulation
hsa-miR-218-5p		Glioblastoma		Suppression
miRBase ID	MIMAT0000275
Interaction Name	hsa-miR-218-5p--MMP2 regulation				[10]
Studied Cell Lines	U373 cell line
Description	hsa-miR-218-5p is reported to suppress MMP2 mRNA translation by binding to the 3' untranslated region (3'UTR) of MMP2 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2.
hsa-miR-708-5p		Glioblastoma		Suppression
miRBase ID	MIMAT0004926
Interaction Name	hsa-miR-708-5p--MMP2 regulation				[11]
Studied Cell Lines	A172 and T98G cell lines
Description	hsa-miR-708-5p is reported to suppress MMP2 mRNA translation by binding to the 3' untranslated region (3'UTR) of MMP2 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2.
ICD-11: 2A83 Multiple myeloma		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
Transcription-factor regulation
Homeobox protein Hox-B7 (HOXB7)		Multiple myeloma		Activation
Uniprot ID	HXB7_HUMAN
Interaction Name	HOXB7-MMP2 interaction				[14]
Studied Cell Lines	Multiple myeloma cell line
Ensembl ID	ENSG00000260027
Description	Homeobox protein Hox-B7 (HOXB7) is reported to activate the transcription of MMP2 gene, which leads to an increased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between HOXB7 and MMP2 can activate the drug-metabolizing process of Matrix metalloproteinase-2.
ICD-11: 2B5F Uterine carcinosarcoma		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
DNA methylation
DNA methyltransferase (DNMT)		Uterine carcinosarcoma		Moderate hypermethylation
Interaction Name	DNMT-MMP-2 interaction
The Methylation Level of Disease Section Compare with the Healthy Individual Tissue	Moderate hypermethylation p-value: 3.74E-03; delta-beta: 2.93E-01
Description	DNA methyltransferase (DNMT) is reported to moderatly hyper-methylate the MMP-2 gene, which leads to a moderatly decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between DNMT and MMP-2 can moderatly affect the drug-metabolizing process of Matrix metalloproteinase-2.
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
ICD-11: 2B5J Fibrosarcoma		Click to Show/Hide the Full List of HOSPPI: 4 HOSPPI
Transcription-factor regulation
Activating TF factor 3 (ATF3)		Fibrosarcoma		Repression
Uniprot ID	ATF3_HUMAN
Interaction Name	ATF3-MMP2 interaction				[15], [16]
Studied Cell Lines	HT1080 cell line
Ensembl ID	ENSG00000162772
Description	Activating TF factor 3 (ATF3) is reported to repress the transcription of MMP2 gene, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between ATF3 and MMP2 can repress the drug-metabolizing process of Matrix metalloproteinase-2.
Nuclear factor kappa-B p105 (NFKB1)		Fibrosarcoma		Activation
Uniprot ID	NFKB1_HUMAN
Interaction Name	NFKB1-MMP2 interaction				[17], [18], [19]
Studied Cell Lines	HT1080 cell line
Ensembl ID	ENSG00000109320
Description	Nuclear factor kappa-B p105 (NFKB1) is reported to activate the transcription of MMP2 gene, which leads to an increased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between NFKB1 and MMP2 can activate the drug-metabolizing process of Matrix metalloproteinase-2.
Transcription factor p65 (RELA)		Fibrosarcoma		Activation
Uniprot ID	TF65_HUMAN
Interaction Name	RELA-MMP2 interaction				[17], [18], [19]
Studied Cell Lines	HT1080 cell line
Ensembl ID	ENSG00000173039
Description	Transcription factor p65 (RELA) is reported to activate the transcription of MMP2 gene, which leads to an increased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between RELA and MMP2 can activate the drug-metabolizing process of Matrix metalloproteinase-2.
Tumor suppressor p53 (TP53)		Fibrosarcoma		Activation
Uniprot ID	P53_HUMAN
Interaction Name	TP53-MMP2 interaction				[20], [15], [21]
Studied Cell Lines	Human fibrosarcoma HT1080 cell line
Ensembl ID	ENSG00000141510
Description	Tumor suppressor p53 (TP53) is reported to activate the transcription of MMP2 gene, which leads to an increased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between TP53 and MMP2 can activate the drug-metabolizing process of Matrix metalloproteinase-2.
ICD-11: 2B71 Gastric cancer		Click to Show/Hide the Full List of HOSPPI: 4 HOSPPI
Transcription-factor regulation
Krueppel-like factor 4 (KLF4)		Gastric cancer		Activation
Uniprot ID	KLF4_HUMAN
Interaction Name	KLF4-MMP2 interaction				[25]
Studied Cell Lines	MKN-45 cell line
Ensembl ID	ENSG00000136826
Description	Krueppel-like factor 4 (KLF4) is reported to activate the transcription of MMP2 gene, which leads to an increased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between KLF4 and MMP2 can activate the drug-metabolizing process of Matrix metalloproteinase-2.
Non-coding RNA regulation
hsa-miR-29c-3p		Gastric cancer		Suppression
miRBase ID	MIMAT0000681
Interaction Name	hsa-miR-29c-3p--MMP2 regulation				[22]
Studied Cell Lines	HGC-27, BGC-823, SGC-7901, MKN-25 and MGC-803 cell lines
Description	hsa-miR-29c-3p is reported to suppress MMP2 mRNA translation by binding to the 3' untranslated region (3'UTR) of MMP2 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2.
hsa-miR-451a		Gastric cancer		Suppression
miRBase ID	MIMAT0001631
Interaction Name	hsa-miR-451a--MMP2 regulation				[23]
Studied Cell Lines	SGC-7901 cell line
Description	hsa-miR-451a is reported to suppress MMP2 mRNA translation by binding to the 3' untranslated region (3'UTR) of MMP2 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2.
hsa-miR-524-5p		Gastric cancer		Suppression
miRBase ID	MIMAT0002849
Interaction Name	hsa-miR-524-5p--MMP2 regulation				[24]
Studied Cell Lines	SGC-7901 and MGC-803 cell lines
Description	hsa-miR-524-5p is reported to suppress MMP2 mRNA translation by binding to the 3' untranslated region (3'UTR) of MMP2 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2.
ICD-11: 2B90 Colorectal cancer		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
Non-coding RNA regulation
hsa-miR-302a-5p		Colorectal cancer		Suppression
miRBase ID	MIMAT0000683
Interaction Name	hsa-miR-302a-5p--MMP2 regulation				[26]
Studied Cell Lines	SW480 cell line
Description	hsa-miR-302a-5p is reported to suppress MMP2 mRNA translation by binding to the 3' untranslated region (3'UTR) of MMP2 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2.
ICD-11: 2C10 Pancreatic adenocarcinoma		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
Transcription-factor regulation
STAT 3 (STAT3)		Pancreatic adenocarcinoma		Activation
Uniprot ID	STAT3_HUMAN
Interaction Name	STAT3-MMP2 interaction				[27], [28], [29]
Studied Cell Lines	SW1990 cell line
Ensembl ID	ENSG00000168610
Description	STAT 3 (STAT3) is reported to activate the transcription of MMP2 gene, which leads to an increased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between STAT3 and MMP2 can activate the drug-metabolizing process of Matrix metalloproteinase-2.
ICD-11: 2C12 Liver cancer		Click to Show/Hide the Full List of HOSPPI: 4 HOSPPI
Non-coding RNA regulation
hsa-miR-143-3p		Liver cancer		Suppression
miRBase ID	MIMAT0000435
Interaction Name	hsa-miR-143-3p--MMP2 regulation				[30]
Studied Cell Lines	HepG2 cell line
Description	hsa-miR-143-3p is reported to suppress MMP2 mRNA translation by binding to the 3' untranslated region (3'UTR) of MMP2 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2.
hsa-miR-17-5p		Liver cancer		Suppression
miRBase ID	MIMAT0000070
Interaction Name	hsa-miR-17-5p--MMP2 regulation				[31]
Studied Cell Lines	Hepatocellular carcinoma cells
Description	hsa-miR-17-5p is reported to suppress MMP2 mRNA translation by binding to the 3' untranslated region (3'UTR) of MMP2 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2.
hsa-miR-221-3p		Liver cancer		Suppression
miRBase ID	MIMAT0000278
Interaction Name	hsa-miR-221-3p--MMP2 regulation				[32]
Studied Cell Lines	HuH28 and HuCCT1 cell lines
Description	hsa-miR-221-3p is reported to suppress MMP2 mRNA translation by binding to the 3' untranslated region (3'UTR) of MMP2 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2.
hsa-miR-491-5p		Liver cancer		Suppression
miRBase ID	MIMAT0002807
Interaction Name	hsa-miR-491-5p--MMP2 regulation				[33]
Studied Cell Lines	HepG2, MHCC97H and MHCC97L cell lines
Description	hsa-miR-491-5p is reported to suppress MMP2 mRNA translation by binding to the 3' untranslated region (3'UTR) of MMP2 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2.
ICD-11: 2C25 Lung cancer		Click to Show/Hide the Full List of HOSPPI: 3 HOSPPI
Transcription-factor regulation
ARNT-interacting protein (HIF1A)		Lung cancer		Activation
Uniprot ID	HIF1A_HUMAN
Interaction Name	HIF1A-MMP2 interaction				[34]
Studied Cell Lines	CL1-5 cell line
Ensembl ID	ENSG00000100644
Description	ARNT-interacting protein (HIF1A) is reported to activate the transcription of MMP2 gene, which leads to an increased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between HIF1A and MMP2 can activate the drug-metabolizing process of Matrix metalloproteinase-2.
Oxidoreductase HTATIP2 (HTATIP2)		Lung cancer		Repression
Uniprot ID	HTAI2_HUMAN
Interaction Name	HTATIP2-MMP2 interaction				[36]
Studied Cell Lines	A549, NCI-H460, SK-MES-1, LTEP-a-2 and H1299 cell lines
Description	Oxidoreductase HTATIP2 (HTATIP2) is reported to repress the transcription of MMP2 gene, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between HTATIP2 and MMP2 can repress the drug-metabolizing process of Matrix metalloproteinase-2.
Non-coding RNA regulation
hsa-miR-29b-3p		Lung cancer		Suppression
miRBase ID	MIMAT0000100
Interaction Name	hsa-miR-29b-3p--MMP2 regulation				[35]
Studied Cell Lines	A549 cell line
Description	hsa-miR-29b-3p is reported to suppress MMP2 mRNA translation by binding to the 3' untranslated region (3'UTR) of MMP2 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2.
ICD-11: 2C60 Breast cancer		Click to Show/Hide the Full List of HOSPPI: 4 HOSPPI
Transcription-factor regulation
Musculin (MSC)		Breast cancer		Activation
Uniprot ID	MUSC_HUMAN
Interaction Name	MSC-MMP2 interaction				[39]
Studied Cell Lines	MDA-MB-231 cell line
Ensembl ID	ENSG00000178860
Description	Musculin (MSC) is reported to activate the transcription of MMP2 gene, which leads to an increased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between MSC and MMP2 can activate the drug-metabolizing process of Matrix metalloproteinase-2.
Transcription factor AP-1 (JUN)		Breast cancer		Activation
Uniprot ID	JUN_HUMAN
Interaction Name	JUN-MMP2 interaction				[40]
Studied Cell Lines	MCF-7, MDA-MB-231, MDA-MB-468 and MDA-MB-435 cell lines
Ensembl ID	ENSG00000177606
Description	Transcription factor AP-1 (JUN) is reported to activate the transcription of MMP2 gene, which leads to an increased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between JUN and MMP2 can activate the drug-metabolizing process of Matrix metalloproteinase-2.
Non-coding RNA regulation
hsa-miR-106b-5p		Breast cancer		Suppression
miRBase ID	MIMAT0000680
Interaction Name	hsa-miR-106b-5p--MMP2 regulation				[37]
Studied Cell Lines	Breast cancer cells
Description	hsa-miR-106b-5p is reported to suppress MMP2 mRNA translation by binding to the 3' untranslated region (3'UTR) of MMP2 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2.
hsa-miR-203a-5p		Breast cancer		Suppression
miRBase ID	MIMAT0031890
Interaction Name	hsa-miR-203a-5p--MMP2 regulation				[38]
Studied Cell Lines	BT474 cell line
Description	hsa-miR-203a-5p is reported to suppress MMP2 mRNA translation by binding to the 3' untranslated region (3'UTR) of MMP2 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2.
ICD-11: 2C73 Ovarian cancer		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
DNA methylation
DNA methyltransferase (DNMT)		Ovarian cancer		Moderate hypermethylation
Interaction Name	DNMT-MMP-2 interaction
The Methylation Level of Disease Section Compare with the Healthy Individual Tissue	Moderate hypermethylation p-value: 8.26E-03; delta-beta: 2.80E-01
Description	DNA methyltransferase (DNMT) is reported to moderatly hyper-methylate the MMP-2 gene, which leads to a moderatly decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between DNMT and MMP-2 can moderatly affect the drug-metabolizing process of Matrix metalloproteinase-2.
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
ICD-11: 2C75 Placenta cancer		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
Non-coding RNA regulation
hsa-miR-519d-3p		Choriocarcinoma		Suppression
miRBase ID	MIMAT0002853
Interaction Name	hsa-miR-519d-3p--MMP2 regulation				[41]
Studied Cell Lines	Human choriocarcinoma JEG-3 cell line
Description	hsa-miR-519d-3p is reported to suppress MMP2 mRNA translation by binding to the 3' untranslated region (3'UTR) of MMP2 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2.
ICD-11: 2C77 Cervical cancer		Click to Show/Hide the Full List of HOSPPI: 2 HOSPPI
Transcription-factor regulation
Enhancer of zeste homolog 2 (EZH2)		Cervical cancer		Activation
Uniprot ID	EZH2_HUMAN
Interaction Name	EZH2-MMP2 interaction				[42]
Studied Cell Lines	Cervical cancer cell line
Description	Enhancer of zeste homolog 2 (EZH2) is reported to activate the transcription of MMP2 gene, which leads to an increased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between EZH2 and MMP2 can activate the drug-metabolizing process of Matrix metalloproteinase-2.
Myeloid zinc finger 1 (MZF1)		Cervical cancer		Repression
Uniprot ID	MZF1_HUMAN
Interaction Name	MZF1-MMP2 interaction				[43]
Studied Cell Lines	SiHa cell line
Ensembl ID	ENSG00000099326
Description	Myeloid zinc finger 1 (MZF1) is reported to repress the transcription of MMP2 gene, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between MZF1 and MMP2 can repress the drug-metabolizing process of Matrix metalloproteinase-2.
ICD-11: 2C82 Prostate cancer		Click to Show/Hide the Full List of HOSPPI: 2 HOSPPI
Non-coding RNA regulation
hsa-miR-130b-3p		Prostate cancer		Suppression
miRBase ID	MIMAT0000691
Interaction Name	hsa-miR-130b-3p--MMP2 regulation				[44]
Studied Cell Lines	M12 cell line
Description	hsa-miR-130b-3p is reported to suppress MMP2 mRNA translation by binding to the 3' untranslated region (3'UTR) of MMP2 mRNA, which leads to a decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2.
DNA methylation
DNA methyltransferase (DNMT)		Prostate cancer		Significant hypermethylation
Interaction Name	DNMT-MMP-2 interaction
The Methylation Level of Disease Section Compare with the Healthy Individual Tissue	Significant hypermethylation p-value: 1.85E-03; delta-beta: 6.45E-01
Description	DNA methyltransferase (DNMT) is reported to significantly hyper-methylate the MMP-2 gene, which leads to a significantly decreased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between DNMT and MMP-2 can significantly affect the drug-metabolizing process of Matrix metalloproteinase-2.
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
ICD-11: 2D10 Thyroid cancer		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
Transcription-factor regulation
Runt transcription factor 2 (RUNX2)		Thyroid cancer		Activation
Uniprot ID	RUNX2_HUMAN
Interaction Name	RUNX2-MMP2 interaction				[45]
Studied Cell Lines	WRO, TPC-1, KTC-1, 8505C, 8305C and TT cell lines
Ensembl ID	ENSG00000124813
Description	Runt transcription factor 2 (RUNX2) is reported to activate the transcription of MMP2 gene, which leads to an increased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between RUNX2 and MMP2 can activate the drug-metabolizing process of Matrix metalloproteinase-2.
ICD Disease Classification 05 Endocrine/nutritional/metabolic diseases
ICD-11: 5B81 Obesity		Click to Show/Hide the Full List of HOSPPI: 1 HOSPPI
DNA methylation
DNA methyltransferase (DNMT)		Obesity		Significant hypomethylation
Interaction Name	DNMT-MMP-2 interaction
The Methylation Level of Disease Section Compare with the Healthy Individual Tissue	Significant hypomethylation p-value: 9.53E-15; delta-beta: -8.02E-01
Description	DNA methyltransferase (DNMT) is reported to significantly hypo-methylate the MMP-2 gene, which leads to a significantly increased expression of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between DNMT and MMP-2 can significantly affect the drug-metabolizing process of Matrix metalloproteinase-2.
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
ICD Disease Classification 08 Nervous system diseases
ICD-11: 8A03 Hereditary ataxia		Click to Show/Hide the Full List of HOSPPI: 2 HOSPPI
Histone modification
Histone deacetylase 3 (HDAC3)		Spinocerebellar ataxia type 3		Repression
Uniprot ID	HDAC3_HUMAN
Interaction Name	HDAC3-MMP2 interaction				[46]
Studied Cell Lines	SCA3 cell model and human brain tissue
Description	Histone deacetylase 3 (HDAC3) is reported to deacetylate the MMP2 gene and thereby represses the transcriptional activity of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between HDAC3 and MMP2 can inhibit the drug-metabolizing process of Matrix metalloproteinase-2.
Histone deacetylase 3 (HDAC3)		Spinocerebellar ataxia type 3		Repression
Uniprot ID	HDAC3_HUMAN
Interaction Name	HDAC3-MMP2 interaction				[46]
Studied Cell Lines	SCA3 cell model and human brain tissue
Description	Histone deacetylase 3 (HDAC3) is reported to deacetylate the MMP2 gene and thereby represses the transcriptional activity of the drug-metabolizing enzyme Matrix metalloproteinase-2. As a result, the interaction between HDAC3 and MMP2 can inhibit the drug-metabolizing process of Matrix metalloproteinase-2.

References
1	Activating transcription factor 2 mediates matrix metalloproteinase-2 transcriptional activation induced by p38 in breast epithelial cells. Cancer Res. 2006 Nov 1;66(21):10487-96.
2	TGF-beta-induced transcriptional activation of MMP-2 is mediated by activating transcription factor (ATF)2 in human breast epithelial cells. Cancer Lett. 2007 Jul 8;252(1):147-56.
3	miR-125b inhibits keratinocyte proliferation and promotes keratinocyte apoptosis in oral lichen planus by targeting MMP-2 expression through PI3K/Akt/mTOR pathway. Biomed Pharmacother. 2016 May;80:373-380.
4	Different regulation of miR-29a-3p in glomeruli and tubules in an experimental model of angiotensin II-dependent hypertension: potential role in renal fibrosis. Clin Exp Pharmacol Physiol. 2016 Mar;43(3):335-42.
5	Elevated microRNA-520g in pre-eclampsia inhibits migration and invasion of trophoblasts. Placenta. 2017 Mar;51:70-75.
6	NUR77 inhibits the expression of TIMP2 and increases the migration and invasion of HTR-8/SVneo cells induced by CYR61. Placenta. 2012 Jul;33(7):561-7.
7	Tissue Inhibitor of metalloproteinase-3 Downregulation in Lymphangioleiomyomatosis: Potential Consequence of Abnormal Serum Response Factor Expression Am J Respir Cell Mol Biol. 2003 Apr;28(4):504-11.
8	Silencing Hypoxia-Inducible factor-1alpha Inhibits Cell Migration and Invasion Under Hypoxic Environment in Malignant Gliomas Int J Oncol. 2007 Apr;30(4):793-802.
9	Interference of HIF-1alpha by RNA reduces the expression of matrix metalloproteinase-2 in human cervical carcinoma HeLa cells. Ai Zheng. 2008 Jun;27(6):600-5.
10	Propofol suppresses proliferation and invasion of glioma cells by upregulating microRNA-218 expression. Mol Med Rep. 2015 Oct;12(4):4815-20.
11	miR-708 acts as a tumor suppressor in human glioblastoma cells. Oncol Rep. 2013 Aug;30(2):870-6.
12	Sp1 is upregulated in human glioma, promotes MMP-2-mediated cell invasion and predicts poor clinical outcome. Int J Cancer. 2012 Feb 1;130(3):593-601.
13	TWIST1 promotes invasion through mesenchymal change in human glioblastoma. Mol Cancer. 2010 Jul 20;9:194.
14	HOXB7 expression by myeloma cells regulates their pro-angiogenic properties in multiple myeloma patients. Leukemia. 2011 Mar;25(3):527-37.
15	ATF3 represses 72-kDa type IV collagenase (MMP-2) expression by antagonizing p53-dependent trans-activation of the collagenase promoter. J Biol Chem. 2002 Mar 29;277(13):10804-12.
16	Nitric oxide inhibits matrix metalloproteinase-2 expression via the induction of activating transcription factor 3 in endothelial cells. Mol Pharmacol. 2004 May;65(5):1130-40.
17	Sulfated glucosamine inhibits MMP-2 and MMP-9 expressions in human fibrosarcoma cells. Bioorg Med Chem. 2007 Jul 15;15(14):4891-6.
18	NF-kappaB inhibition in human hepatocellular carcinoma and its potential as adjunct to sorafenib based therapy. Cancer Lett. 2009 Jun 18;278(2):145-155.
19	Ursolic acid, a naturally occurring triterpenoid, suppresses migration and invasion of human breast cancer cells by modulating c-Jun N-terminal kinase, Akt and mammalian target of rapamycin signaling. Mol Nutr Food Res. 2010 Sep;54(9):1285-95.
20	Regulation of metastasis-related gene expression by p53: a potential clinical implication. Mol Carcinog. 1999 Jan;24(1):25-8.
21	Transcriptional activation by p53 of the human type IV collagenase (gelatinase A or matrix metalloproteinase 2) promoter. Mol Cell Biol. 1997 Nov;17(11):6330-8.
22	Characterization of microRNA-29 family expression and investigation of their mechanistic roles in gastric cancer. Carcinogenesis. 2014 Feb;35(2):497-506.
23	Propofol inhibits proliferation and accelerates apoptosis of human gastric cancer cells by regulation of microRNA-451 and MMP-2 expression. Genet Mol Res. 2016 Apr 4;15(2).
24	MicroRNA-524-5p suppresses the growth and invasive abilities of gastric cancer cells. Oncol Lett. 2016 Mar;11(3):1926-1932.
25	Krppel-like factor 4 negatively regulates beta-catenin expression and inhibits the proliferation, invasion and metastasis of gastric cancer. Int J Oncol. 2012 Jun;40(6):2038-48.
26	Up-regulation of microRNA-302a inhibited the proliferation and invasion of colorectal cancer cells by regulation of the MAPK and PI3K/Akt signaling pathways. Int J Clin Exp Pathol. 2015 May 1;8(5):4481-91.
27	Inhibitory effect of AG490 on invasion and metastasis of human pancreatic cancer cells in vitro. Zhonghua Zhong Liu Za Zhi. 2006 Dec;28(12):890-3.
28	Characterization of STAT3 activation and expression in canine and human osteosarcoma. BMC Cancer. 2009 Mar 10;9:81.
29	Down-regulation of Stat3 decreases invasion activity and induces apoptosis of human glioma cells. J Mol Neurosci. 2010 Mar;40(3):353-9.
30	miR-143 down-regulates TLR2 expression in hepatoma cells and inhibits hepatoma cell proliferation and invasion. Int J Clin Exp Pathol. 2015 Oct 1;8(10):12738-47.
31	miR-17-5p Promotes migration of human hepatocellular carcinoma cells through the p38 mitogen-activated protein kinase-heat shock protein 27 pathway. Hepatology. 2010 May;51(5):1614-23.
32	miR-29b, miR-205 and miR-221 enhance chemosensitivity to gemcitabine in HuH28 human cholangiocarcinoma cells. PLoS One. 2013 Oct 17;8(10):e77623.
33	MicroRNA-491 is involved in metastasis of hepatocellular carcinoma by inhibitions of matrix metalloproteinase and epithelial to mesenchymal transition. Liver Int. 2013 Sep;33(8):1271-80.
34	Hypoxia-inducible factor 1alpha regulates lung adenocarcinoma cell invasion. Exp Cell Res. 2007 Apr 1;313(6):1181-91.
35	MicroRNA-29b attenuates non-small cell lung cancer metastasis by targeting matrix metalloproteinase 2 and PTEN. J Exp Clin Cancer Res. 2015 Jun 11;34(1):59.
36	Decreased TIP30 expression promotes tumor metastasis in lung cancer. Am J Pathol. 2009 May;174(5):1931-9.
37	Downregulation of miR-106b induced breast cancer cell invasion and motility in association with overexpression of matrix metalloproteinase 2. Cancer Sci. 2014 Jan;105(1):18-25.
38	MicroRNA-203 Regulates Growth and Metastasis of Breast Cancer. Cell Physiol Biochem. 2015;37(1):35-42.
39	Effects of Se-methylselenocysteine on biological behavior of and matrix metalloproteinase-2 expression in human breast cancer MDA-MB-231 cells. Ai Zheng. 2008 Feb;27(2):119-25.
40	Cell density-dependent regulation of matrix metalloproteinase and TIMP expression in differently tumorigenic breast cancer cell lines. Exp Cell Res. 2005 Apr 15;305(1):83-98.
41	MiR-519d-3p suppresses invasion and migration of trophoblast cells via targeting MMP-2. PLoS One. 2015 Mar 24;10(3):e0120321.
42	Enhancer of zeste homolog 2 expression is associated with tumor cell proliferation and invasion in cervical cancer. Am J Med Sci. 2011 Sep;342(3):198-204.
43	Overexpression of myeloid zinc finger 1 suppresses matrix metalloproteinase-2 expression and reduces invasiveness of SiHa human cervical cancer cells. Biochem Biophys Res Commun. 2012 Aug 24;425(2):462-7.
44	MiR-130b suppresses prostate cancer metastasis through down-regulation of MMP2. Mol Carcinog. 2015 Nov;54(11):1292-300.
45	Transcription factor Runx2 is a regulator of epithelial-mesenchymal transition and invasion in thyroid carcinomas. Lab Invest. 2012 Aug;92(8):1181-90.
46	Ataxin-3 represses transcription via chromatin binding, interaction with histone deacetylase 3, and histone deacetylation. J Neurosci. 2006 Nov 1;26(44):11474-86.

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