Molecule Information

General Information of the Molecule (ID: Mol00172)

• Name: Protein sprouty homolog 2 (SPRY2) ,Homo sapiens
• Synonyms: Spry-2
• Molecule Type: Protein
• Gene Name: SPRY2
• Gene ID: 10253
• Location: chr13:80335976-80341126[-]
• Sequence:
  MEARAQSGNGSQPLLQTPRDGGRQRGEPDPRDALTQQVHVLSLDQIRAIRNTNEYTEGPT
  VVPRPGLKPAPRPSTQHKHERLHGLPEHRQPPRLQHSQVHSSARAPLSRSISTVSSGSRS
  STRTSTSSSSSEQRLLGSSFSSGPVADGIIRVQPKSELKPGELKPLSKEDLGLHAYRCED
  CGKCKCKECTYPRPLPSDWICDKQCLCSAQNVIDYGTCVCCVKGLFYHCSNDDEDNCADN
  PCSCSQSHCCTRWSAMGVMSLFLPCLWCYLPAKGCLKLCQGCYDRVNRPGCRCKNSNTVC
  CKVPTVPPRNFEKPT
• Function: Antagonist of fibroblast growth factor (FGF) pathways via inhibition of FGF-mediated phosphorylation of ERK1/2. Thereby acts as an antagonist of FGF-induced retinal lens fiber differentiation, may inhibit limb bud outgrowth and may negatively modulate respiratory organogenesis. Inhibits TGFB-induced epithelial-to-mesenchymal transition in retinal lens epithelial cells. Inhibits CBL/C-CBL-mediated EGFR ubiquitination.
• Uniprot ID: SPY2_HUMAN
• Ensembl ID: ENSG00000136158
• HGNC ID: HGNC:11270

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

Type(s) of Resistant Mechanism of This Molecule

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Carmustine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Glioma [1]

• Resistant Disease: Glioma [ICD-11: 2A00.1]
• Resistant Drug: Carmustine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SWOZ2 cells; Brain; Homo sapiens (Human); N.A.
• In Vitro Model: SWOZ2-BCNU cells; Brain; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR21 enhanced glioma cells resistance to carmustine via decreasing Spry2 expression.

Cisplatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Osteosarcoma [2]

• Sensitive Disease: Osteosarcoma [ICD-11: 2B51.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: MG63 cells; Bone marrow; Homo sapiens (Human); CVCL_0426
• In Vitro Model: SAOS-2 cells; Bone marrow; Homo sapiens (Human); CVCL_0548
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• In Vitro Model: HOS cells; Bone; Homo sapiens (Human); CVCL_0312
• In Vitro Model: 143B cells; Bone; Homo sapiens (Human); CVCL_2270
• In Vitro Model: HLNG cells; Bone marrow; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Northern blotting
• Experiment for Drug Resistance: Scratch assay
• Mechanism Description: miR-21 regulatory network plays a role in tumorigenesis of osteosarcoma. Its expression facilitates cell proliferation and decreases cellular sensitivity towards cisplatin. Both effects can be rescued by Spry2, a target protein downregulated by increased miR-21 levels.

Docetaxel

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Prostate cancer [3]

• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Sensitive Drug: Docetaxel
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: ERK signaling pathway; Regulation; hsa04210
• Cell Pathway Regulation: RTK signaling pathway; Inhibition; hsa04015
• 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: RWPE-1 cells; Prostate; Homo sapiens (Human); CVCL_3791
• In Vitro Model: C4-2 cells; Prostate; Homo sapiens (Human); CVCL_4782
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometer assay
• Mechanism Description: SPRY2 is a direct downstream target of miR183 and can be negatively regulated by miR183 and is regarded as a negative regulator RTk signaling pathway, antagonizing cell migration and/or cellular differentiation occurring through the ERk signaling. CASC2 competes with SPRY2 for miR183 binding to rescue the expression of SPRY2 in PC cells, thus suppressing the cell proliferation and promoting the apoptosis of PC cells, finally enhancing PC cells chemo-sensitivity to docetaxel through SPRY2 downstream ERk signaling pathway.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Brain cancer [ICD-11: 2A00]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Nervous tissue
• The Specified Disease: Brain cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.47E-13; Fold-change: 4.09E-01; Z-score: 6.80E-01
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.74E-09; Fold-change: 9.03E-01; Z-score: 2.94E+01
• The Studied Tissue: White matter
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.85E-02; Fold-change: 7.74E-01; Z-score: 1.36E+00
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Neuroectodermal tumor
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.29E-01; Fold-change: 2.87E-01; Z-score: 5.05E-01

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: 1.64E-02; Fold-change: -1.35E-01; Z-score: -1.74E-01

References

• Ref 1: MiR-21 enhanced glioma cells resistance to carmustine via decreasing Spry2 expression. Eur Rev Med Pharmacol Sci. 2017 Nov;21(22):5065-5071. doi: 10.26355/eurrev_201711_13819.
• Ref 2: MicroRNA-21 Increases Proliferation and Cisplatin Sensitivity of Osteosarcoma-Derived Cells. PLoS One. 2016 Aug 11;11(8):e0161023. doi: 10.1371/journal.pone.0161023. eCollection 2016.
• Ref 3: Long non-coding RNA CASC2 regulates Sprouty2 via functioning as a competing endogenous RNA for miR-183 to modulate the sensitivity of prostate cancer cells to docetaxel. Arch Biochem Biophys. 2019 Apr 15;665:69-78. doi: 10.1016/j.abb.2018.01.013. Epub 2018 Jan 31.