Molecule Information

General Information of the Molecule (ID: Mol00142)

• Name: Peroxisome proliferator-activated receptor gamma (PPARG) ,Homo sapiens
• Synonyms: PPAR-gamma; Nuclear receptor subfamily 1 group C member 3; NR1C3
• Molecule Type: Protein
• Gene Name: PPARG
• Gene ID: 5468
• Location: chr3:12287368-12434356[+]
• Sequence:
  MGETLGDSPIDPESDSFTDTLSANISQEMTMVDTEMPFWPTNFGISSVDLSVMEDHSHSF
  DIKPFTTVDFSSISTPHYEDIPFTRTDPVVADYKYDLKLQEYQSAIKVEPASPPYYSEKT
  QLYNKPHEEPSNSLMAIECRVCGDKASGFHYGVHACEGCKGFFRRTIRLKLIYDRCDLNC
  RIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEKLLAEISSDIDQLNPESADLR
  ALAKHLYDSYIKSFPLTKAKARAILTGKTTDKSPFVIYDMNSLMMGEDKIKFKHITPLQE
  QSKEVAIRIFQGCQFRSVEAVQEITEYAKSIPGFVNLDLNDQVTLLKYGVHEIIYTMLAS
  LMNKDGVLISEGQGFMTREFLKSLRKPFGDFMEPKFEFAVKFNALELDDSDLAIFIAVII
  LSGDRPGLLNVKPIEDIQDNLLQALELQLKLNHPESSQLFAKLLQKMTDLRQIVTEHVQL
  LQVIKKTETDMSLHPLLQEIYKDLY
• Function: Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (By similarity).
• Uniprot ID: PPARG_HUMAN
• Ensembl ID: ENSG00000132170
• HGNC ID: HGNC:9236

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) 2 drug(s) in total

Doxorubicin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Anaplastic thyroid carcinoma [1]

• Sensitive Disease: Anaplastic thyroid carcinoma [ICD-11: 2D10.3]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: miR27b-3p/PPARgamma signaling pathway; Regulation; hsa05206
• In Vitro Model: 8305C cells; Thyroid; Homo sapiens (Human); CVCL_1053
• In Vitro Model: SW1736 cells; Thyroid; Homo sapiens (Human); CVCL_3883
• Experiment for Molecule Alteration: Western blot analysis; RIP assay; Luciferase reporter assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: The inhibitor of miR-27b-3p can increase the Dox sensitivity of ATC Dox-resistant cells while over-expression of PPARGamma also increased the Dox sensitivity of ATC-resistant cells.

Gemcitabine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Cholangiocarcinoma [2]

• Resistant Disease: Cholangiocarcinoma [ICD-11: 2C12.0]
• Resistant Drug: Gemcitabine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: CCLP-1 cells; Liver; Homo sapiens (Human); CVCL_0205
• In Vitro Model: MzChA-1 cells; Liver; Homo sapiens (Human); CVCL_6932
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Transfection of miR130a-3p mimic suppressed the expression of PPARG and increased gemcitabine resistance.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Liver cancer [ICD-11: 2C12]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Liver
• The Specified Disease: Liver cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.02E-03; Fold-change: 1.94E-01; Z-score: 3.22E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 3.83E-18; Fold-change: 4.53E-01; Z-score: 9.76E-01
• The Expression Level of Disease Section Compare with the Other Disease Section: p-value: 1.70E-01; Fold-change: 1.42E-01; Z-score: 7.72E-01

Thyroid cancer [ICD-11: 2D10]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Thyroid
• The Specified Disease: Thyroid cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.86E-27; Fold-change: -1.01E+00; Z-score: -2.02E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 6.90E-14; Fold-change: -1.06E+00; Z-score: -1.95E+00

References

• Ref 1: miR-27b-3p is Involved in Doxorubicin Resistance of Human Anaplastic Thyroid Cancer Cells via Targeting Peroxisome Proliferator-Activated Receptor Gamma. Basic Clin Pharmacol Toxicol. 2018 Dec;123(6):670-677. doi: 10.1111/bcpt.13076. Epub 2018 Aug 5.
• Ref 2: Micro-RNA-130a-3p Regulates Gemcitabine Resistance via PPARG in Cholangiocarcinoma. Ann Surg Oncol. 2017 Aug;24(8):2344-2352. doi: 10.1245/s10434-017-5871-x. Epub 2017 May 30.