Molecule Information

General Information of the Molecule (ID: Mol00179)

• Name: Transforming growth factor beta 1 (TGFB1) ,Homo sapiens
• Synonyms: LAP; TGF-beta-1; TGFB
• Molecule Type: Protein
• Gene Name: TGFB1
• Gene ID: 7040
• Location: chr19:41301587-41353922[-]
• Sequence:
  MPPSGLRLLLLLLPLLWLLVLTPGRPAAGLSTCKTIDMELVKRKRIEAIRGQILSKLRLA
  SPPSQGEVPPGPLPEAVLALYNSTRDRVAGESAEPEPEPEADYYAKEVTRVLMVETHNEI
  YDKFKQSTHSIYMFFNTSELREAVPEPVLLSRAELRLLRLKLKVEQHVELYQKYSNNSWR
  YLSNRLLAPSDSPEWLSFDVTGVVRQWLSRGGEIEGFRLSAHCSCDSRDNTLQVDINGFT
  TGRRGDLATIHGMNRPFLLLMATPLERAQHLQSSRHRRALDTNYCFSSTEKNCCVRQLYI
  DFRKDLGWKWIHEPKGYHANFCLGPCPYIWSLDTQYSKVLALYNQHNPGASAAPCCVPQA
  LEPLPIVYYVGRKPKVEQLSNMIVRSCKCS
• Function: Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively.
• Uniprot ID: TGFB1_HUMAN
• Ensembl ID: ENSG00000105329
• HGNC ID: HGNC:11766

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

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

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

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Ovarian cancer [1]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: A2780/DDP cells; Ovary; Homo sapiens (Human); CVCL_D619
• In Vitro Model: SkOV-3/DDP cells; Ovary; Homo sapiens (Human); CVCL_UI88
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: PVT1 was overexpressed in tumor tissues of cisplatin-resistant patients comparing to cisplatin-sensitive patients. PVT1 knockdown significantly lowered cell viability and increased the percentage of apoptotic tumor cells in SkOV-3/DDP and A2780/DDP cells transfected with siPVT1 and treated with cisplatin. It manifested PVT1 knockdown can reverses the cisplatin resistance in cisplatin-resistant cell lines.

Fluorouracil

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Disease Class: Gastric cancer [2]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Resistant Drug: Fluorouracil
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: FAO signaling pathway; Activation; hsa04550
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Enzyme-linked immunosorbent assay
• Experiment for Drug Resistance: MTT assay; Colony formation assays
• Mechanism Description: Transforming growth factor beta1 (TGF-beta1) secretion by MSCs activated SMAD2/3 through TGF-beta receptors and induced long non-coding RNA (LncRNA) MACC1-AS1 expression in GC cells, which promoted FAO-dependent stemness and chemoresistance through antagonizing miR-145-5p.

Oxaliplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Disease Class: Gastric cancer [2]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Resistant Drug: Oxaliplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: FAO signaling pathway; Activation; hsa04550
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Enzyme-linked immunosorbent assay
• Experiment for Drug Resistance: MTT assay; Colony formation assays
• Mechanism Description: Transforming growth factor beta1 (TGF-beta1) secretion by MSCs activated SMAD2/3 through TGF-beta receptors and induced long non-coding RNA (LncRNA) MACC1-AS1 expression in GC cells, which promoted FAO-dependent stemness and chemoresistance through antagonizing miR-145-5p.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Gastric cancer [ICD-11: 2B72]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Gastric tissue
• The Specified Disease: Gastric cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.13E-01; Fold-change: 2.73E-01; Z-score: 1.18E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 2.01E-02; Fold-change: 1.17E+00; Z-score: 1.36E+00

Ovarian cancer [ICD-11: 2C73]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Ovary
• The Specified Disease: Ovarian cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.96E-01; Fold-change: -4.33E-02; Z-score: -7.23E-02
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 4.63E-01; Fold-change: 5.98E-01; Z-score: 6.51E-01

References

• Ref 1: Overexpression of long non-coding RNA PVT1 in ovarian cancer cells promotes cisplatin resistance by regulating apoptotic pathways. Int J Clin Exp Med. 2015 Nov 15;8(11):20565-72. eCollection 2015.
• Ref 2: MSC-regulated lncRNA MACC1-AS1 promotes stemness and chemoresistance through fatty acid oxidation in gastric cancer. Oncogene. 2019 Jun;38(23):4637-4654. doi: 10.1038/s41388-019-0747-0. Epub 2019 Feb 11.