Disease Information

General Information of the Disease (ID: DIS00064)
Name
Synovial sarcoma
ICD
ICD-11: 2B5A
Resistance Map
Type(s) of Resistant Mechanism of This Disease
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
2 drug(s) in total
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Doxorubicin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-17 [1]
Resistant Disease Synovial sarcoma [ICD-11: 2B5A.0]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Doxorubicin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
p21 Regulation
In Vitro Model HS-SYII cells Sarcoma Homo sapiens (Human) CVCL_8719
SYO-1 cells Sarcoma Homo sapiens (Human) CVCL_7146
Fuji cells Sarcoma Homo sapiens (Human) CVCL_D880
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 Colony formation assay
Mechanism Description Overexpression of miR-17 in synovial sarcoma cells, Fuji and HS-SYII, increased colony forming ability in addition to cell growth, but not cell motility and invasion. Tumor volume formed in mice in vivo was significantly increased by miR-17 overexpression with a marked increase of MIB-1 index. According to PicTar and Miranda algorithms, which predicted CDkN1A (p21) as a putative target of miR-17, a luciferase assay was performed and revealed that miR-17 directly targets the 3'-UTR of p21 mRNA. Indeed, p21 protein level was remarkably decreased by miR-17 overexpression in a p53-independent manner. It is noteworthy that miR-17 succeeded in suppressing doxorubicin-evoked higher expression of p21 and conferred the drug resistance. Meanwhile, introduction of anti-miR-17 in Fuji and HS-SYII cells significantly decreased cell growth, consistent with rescued expression of p21.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Ribonuclease P protein subunit p21 (RPP21) [1]
Resistant Disease Synovial sarcoma [ICD-11: 2B5A.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Doxorubicin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
p21 Regulation
In Vitro Model HS-SYII cells Sarcoma Homo sapiens (Human) CVCL_8719
SYO-1 cells Sarcoma Homo sapiens (Human) CVCL_7146
Fuji cells Sarcoma Homo sapiens (Human) CVCL_D880
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Colony formation assay
Mechanism Description Overexpression of miR-17 in synovial sarcoma cells, Fuji and HS-SYII, increased colony forming ability in addition to cell growth, but not cell motility and invasion. Tumor volume formed in mice in vivo was significantly increased by miR-17 overexpression with a marked increase of MIB-1 index. According to PicTar and Miranda algorithms, which predicted CDkN1A (p21) as a putative target of miR-17, a luciferase assay was performed and revealed that miR-17 directly targets the 3'-UTR of p21 mRNA. Indeed, p21 protein level was remarkably decreased by miR-17 overexpression in a p53-independent manner. It is noteworthy that miR-17 succeeded in suppressing doxorubicin-evoked higher expression of p21 and conferred the drug resistance. Meanwhile, introduction of anti-miR-17 in Fuji and HS-SYII cells significantly decreased cell growth, consistent with rescued expression of p21.
Pazopanib HCl
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: Prelamin-A/C (LMNA) [2]
Resistant Disease Synovial sarcoma [ICD-11: 2B5A.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Pazopanib HCl
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model 1273/99 cells Sarcoma Homo sapiens (Human) CVCL_N588
HS-SYII cells Sarcoma Homo sapiens (Human) CVCL_8719
SYO-1 cells Sarcoma Homo sapiens (Human) CVCL_7146
YaFuSS cells Sarcoma Homo sapiens (Human) CVCL_L809
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 EV isolation, immunoblotting, and nanoparticle tracking analysis
Mechanism Description Extracellular vesicle-encapsulated microRNA-761 enhances pazopanib resistance in synovial sarcoma by down-regulating TRIP6, LMNA, and SIRT3 expression.
Key Molecule: hsa-miR-761 [2]
Resistant Disease Synovial sarcoma [ICD-11: 2B5A.0]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Pazopanib HCl
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model 1273/99 cells Sarcoma Homo sapiens (Human) CVCL_N588
HS-SYII cells Sarcoma Homo sapiens (Human) CVCL_8719
SYO-1 cells Sarcoma Homo sapiens (Human) CVCL_7146
YaFuSS cells Sarcoma Homo sapiens (Human) CVCL_L809
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 EV isolation, immunoblotting, and nanoparticle tracking analysis
Mechanism Description Extracellular vesicle-encapsulated microRNA-761 enhances pazopanib resistance in synovial sarcoma by down-regulating TRIP6, LMNA, and SIRT3 expression.
Key Molecule: NAD-dependent protein deacetylase sirtuin-3 (SIRT3) [2]
Resistant Disease Synovial sarcoma [ICD-11: 2B5A.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Pazopanib HCl
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model 1273/99 cells Sarcoma Homo sapiens (Human) CVCL_N588
HS-SYII cells Sarcoma Homo sapiens (Human) CVCL_8719
SYO-1 cells Sarcoma Homo sapiens (Human) CVCL_7146
YaFuSS cells Sarcoma Homo sapiens (Human) CVCL_L809
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 EV isolation, immunoblotting, and nanoparticle tracking analysis
Mechanism Description Extracellular vesicle-encapsulated microRNA-761 enhances pazopanib resistance in synovial sarcoma by down-regulating TRIP6, LMNA, and SIRT3 expression.
Key Molecule: Thyroid receptor-interacting protein 6 (TRIP6) [2]
Resistant Disease Synovial sarcoma [ICD-11: 2B5A.0]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Pazopanib HCl
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model 1273/99 cells Sarcoma Homo sapiens (Human) CVCL_N588
HS-SYII cells Sarcoma Homo sapiens (Human) CVCL_8719
SYO-1 cells Sarcoma Homo sapiens (Human) CVCL_7146
YaFuSS cells Sarcoma Homo sapiens (Human) CVCL_L809
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 EV isolation, immunoblotting, and nanoparticle tracking analysis
Mechanism Description Extracellular vesicle-encapsulated microRNA-761 enhances pazopanib resistance in synovial sarcoma by down-regulating TRIP6, LMNA, and SIRT3 expression.
References
Ref 1 SS18-SSX-regulated miR-17 promotes tumor growth of synovial sarcoma by inhibiting p21WAF1/CIP1. Cancer Sci. 2014 Sep;105(9):1152-9. doi: 10.1111/cas.12479. Epub 2014 Sep 3.
Ref 2 Extracellular vesicle-encapsulated microRNA-761 enhances pazopanib resistance in synovial sarcoma. Biochem Biophys Res Commun. 2018 Jan 1;495(1):1322-1327. doi: 10.1016/j.bbrc.2017.11.164. Epub 2017 Nov 27.

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