Disease Information

General Information of the Disease (ID: DIS00064)

• Name: Synovial sarcoma
• ICD: ICD-11: 2B5A

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

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-17 [1]

• Resistant Disease: Synovial sarcoma [ICD-11: 2B5A.0]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: p21; Regulation; N.A.
• In Vitro Model: HS-SYII cells; Sarcoma; Homo sapiens (Human); CVCL_8719
• In Vitro Model: SYO-1 cells; Sarcoma; Homo sapiens (Human); CVCL_7146
• In Vitro Model: 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)

Key Molecule: Ribonuclease P protein subunit p21 (RPP21) [1]

• Resistant Disease: Synovial sarcoma [ICD-11: 2B5A.0]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: p21; Regulation; N.A.
• In Vitro Model: HS-SYII cells; Sarcoma; Homo sapiens (Human); CVCL_8719
• In Vitro Model: SYO-1 cells; Sarcoma; Homo sapiens (Human); CVCL_7146
• In Vitro Model: 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

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Prelamin-A/C (LMNA) [2]

• Resistant Disease: Synovial sarcoma [ICD-11: 2B5A.0]
• Resistant Drug: Pazopanib HCl
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 1273/99 cells; Sarcoma; Homo sapiens (Human); CVCL_N588
• In Vitro Model: HS-SYII cells; Sarcoma; Homo sapiens (Human); CVCL_8719
• In Vitro Model: SYO-1 cells; Sarcoma; Homo sapiens (Human); CVCL_7146
• In Vitro Model: 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]
• Resistant Drug: Pazopanib HCl
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 1273/99 cells; Sarcoma; Homo sapiens (Human); CVCL_N588
• In Vitro Model: HS-SYII cells; Sarcoma; Homo sapiens (Human); CVCL_8719
• In Vitro Model: SYO-1 cells; Sarcoma; Homo sapiens (Human); CVCL_7146
• In Vitro Model: 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]
• Resistant Drug: Pazopanib HCl
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 1273/99 cells; Sarcoma; Homo sapiens (Human); CVCL_N588
• In Vitro Model: HS-SYII cells; Sarcoma; Homo sapiens (Human); CVCL_8719
• In Vitro Model: SYO-1 cells; Sarcoma; Homo sapiens (Human); CVCL_7146
• In Vitro Model: 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]
• Resistant Drug: Pazopanib HCl
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 1273/99 cells; Sarcoma; Homo sapiens (Human); CVCL_N588
• In Vitro Model: HS-SYII cells; Sarcoma; Homo sapiens (Human); CVCL_8719
• In Vitro Model: SYO-1 cells; Sarcoma; Homo sapiens (Human); CVCL_7146
• In Vitro Model: 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.