Molecule Information

General Information of the Molecule (ID: Mol00118)

• Name: Matrix metalloproteinase-9 (MMP9) ,Homo sapiens
• Synonyms: MMP-9; 92 kDa gelatinase; 92 kDa type IV collagenase; Gelatinase B; GELB; CLG4B
• Molecule Type: Protein
• Gene Name: MMP9
• Gene ID: 4318
• Location: chr20:46008908-46016561[+]
• Sequence:
  MSLWQPLVLVLLVLGCCFAAPRQRQSTLVLFPGDLRTNLTDRQLAEEYLYRYGYTRVAEM
  RGESKSLGPALLLLQKQLSLPETGELDSATLKAMRTPRCGVPDLGRFQTFEGDLKWHHHN
  ITYWIQNYSEDLPRAVIDDAFARAFALWSAVTPLTFTRVYSRDADIVIQFGVAEHGDGYP
  FDGKDGLLAHAFPPGPGIQGDAHFDDDELWSLGKGVVVPTRFGNADGAACHFPFIFEGRS
  YSACTTDGRSDGLPWCSTTANYDTDDRFGFCPSERLYTQDGNADGKPCQFPFIFQGQSYS
  ACTTDGRSDGYRWCATTANYDRDKLFGFCPTRADSTVMGGNSAGELCVFPFTFLGKEYST
  CTSEGRGDGRLWCATTSNFDSDKKWGFCPDQGYSLFLVAAHEFGHALGLDHSSVPEALMY
  PMYRFTEGPPLHKDDVNGIRHLYGPRPEPEPRPPTTTTPQPTAPPTVCPTGPPTVHPSER
  PTAGPTGPPSAGPTGPPTAGPSTATTVPLSPVDDACNVNIFDAIAEIGNQLYLFKDGKYW
  RFSEGRGSRPQGPFLIADKWPALPRKLDSVFEERLSKKLFFFSGRQVWVYTGASVLGPRR
  LDKLGLGADVAQVTGALRSGRGKMLLFSGRRLWRFDVKAQMVDPRSASEVDRMFPGVPLD
  THDVFQYREKAYFCQDRFYWRVSSRSELNQVDQVGYVTYDILQCPED
• Function: Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves NINJ1 to generate the Secreted ninjurin-1 form. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.
• Uniprot ID: MMP9_HUMAN
• Ensembl ID: ENSG00000100985
• HGNC ID: HGNC:7176

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  RTDM: Regulation by the Disease Microenvironment

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Cisplatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Disease Class: Prostate cancer [1]

• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: ERK signaling pathway; Inhibition; hsa04210
• Cell Pathway Regulation: Epithelial mesenchymal transition signaling pathway; Inhibition; hsa01521
• In Vitro Model: DU-145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: LNCaP cells; Prostate; Homo sapiens (Human); CVCL_0395
• In Vitro Model: PC3 cells; Prostate; Homo sapiens (Human); CVCL_0035
• In Vitro Model: VCaP cells; Prostate; Homo sapiens (Human); CVCL_2235
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: UTMD mediated miR 205 transfection increased the expression of caspase 9, cleaved caspase 9, cytochrome c and E cadherin, and decreased the expression of MMP 9 and p ERk,inhibiting PCa cell proliferation, migration and invasion, and promoted apoptosis modulated by cisplatin.

Silibinin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Disease Class: Osteosarcoma [2]

• Sensitive Disease: Osteosarcoma [ICD-11: 2B51.0]
• Sensitive Drug: Silibinin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: MG63 cells; Bone marrow; Homo sapiens (Human); CVCL_0426
• Experiment for Molecule Alteration: qPCR; Western blot analysis
• Experiment for Drug Resistance: TUNEL cell apoptosis assay; XTT cell proliferation assay; MTT cell proliferation assay; Colony formation assay
• Mechanism Description: MMP-9 was targeted and negatively regulated by hsa-miR494 which inhibited cell proliferation and induced cell apoptosis. Silybin inhibited OS cell viability by altering the protein levels of beta-catenin and RUNX2, thus upregulating the level of hsa-miR494.

Investigative Drug(s) 1 drug(s) in total

Platinum

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Disease Class: Breast cancer [3]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Platinum
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Caspase 3/7 cleavage assays; Aldefluor assay; MTS assay; Flow cytometric analysis
• Mechanism Description: Blocking the EZH2-interactiing domain of HOTAIR and disrupting the HOTAIR-EZH2 interaction resensitizes cancer cells to clinically relevant cytotoxic chemotherapies, reduces cell invasion and decreases NF-kB transcriptional activity and IL-6 and MMP-9 expression in vivo. Levels of genes like MMP9 shown to be up-regulated by HOTAIR.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Breast cancer [ICD-11: 2C60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Breast tissue
• The Specified Disease: Breast cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.35E-110; Fold-change: 2.48E+00; Z-score: 2.34E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 4.47E-08; Fold-change: 1.91E+00; Z-score: 1.20E+00

Prostate cancer [ICD-11: 2C82]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Prostate
• The Specified Disease: Prostate cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.62E-01; Fold-change: 5.13E-02; Z-score: 4.24E-02

References

• Ref 1: Ultrasound targeted microbubble destruction mediated miR 205 enhances cisplatin cytotoxicity in prostate cancer cells. Mol Med Rep. 2018 Sep;18(3):3242-3250. doi: 10.3892/mmr.2018.9316. Epub 2018 Jul 24.
• Ref 2: Matrix metallopeptidase 9 targeted by hsa-miR-494 promotes silybin-inhibited osteosarcoma. Mol Carcinog. 2018 Feb;57(2):262-271. doi: 10.1002/mc.22753. Epub 2017 Nov 2.
• Ref 3: Therapeutic targeting using tumor specific peptides inhibits long non-coding RNA HOTAIR activity in ovarian and breast cancer. Sci Rep. 2017 Apr 18;7(1):894. doi: 10.1038/s41598-017-00966-3.