Molecule Information

General Information of the Molecule (ID: Mol01958)

• Name: TNF alpha induced protein 8 (TNFAIP8) ,Homo sapiens
• Synonyms: TNFAIP8
• Molecule Type: Protein
• Gene Name: TNFAIP8
• Gene ID: 25816
• Location: chr5:119,268,692-119,399,688[+]
• Sequence:
  MHSEAEESKEVATDVFNSKNLAVQAQKKILGKMVSKSIATTLIDDTSSEVLDELYRVTRE
  YTQNKKEAEKIIKNLIKTVIKLAILYRNNQFNQDELALMEKFKKKVHQLAMTVVSFHQVD
  YTFDRNVLSRLLNECREMLHQIIQRHLTAKSHGRVNNVFDHFSDCEFLAALYNPFGNFKP
  HLQKLCDGINKMLDEENI
• Function: Acts as a negative mediator of apoptosis and may play a role in tumor progression. Suppresses the TNF-mediated apoptosis by inhibiting caspase-8 activity but not the processing of procaspase-8, subsequently resulting in inhibition of BID cleavage and caspase-3 activation.
• Uniprot ID: TFIP8_HUMAN
• Ensembl ID: ENSG00000145779
• HGNC ID: HGNC:17260

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

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Sorafenib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Hepatic Steatosis [1]

• Resistant Disease: Hepatic Steatosis [ICD-11: DB92.Y]
• Resistant Drug: Sorafenib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: AKT/mTOR signaling pathway; Inhibition; hsa04150
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: SK-Hep1 cells; Ascites; Homo sapiens (Human); CVCL_0525
• In Vitro Model: PLC/PRF/5 cells; Liver; Homo sapiens (Human); CVCL_0485
• In Vivo Model: C57BL/6J mice; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; RT/qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Increased TNFAIP8 levels in HCC cells enhanced cell survival by blocking apoptosis, rendering HCC cells more resistant to the anticancer drugs, sorafenib and regorafenib. TNFAIP8 also induced autophagy and steatosis in liver cancer cells. Consistent with these observations, TNFAIP8 blocked AKT/mTOR signaling and showed direct interaction with ATG3-ATG7 proteins.

Disease Class: Hepatic Steatosis [1]

• Resistant Disease: Hepatic Steatosis [ICD-11: DB92.Y]
• Resistant Drug: Sorafenib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: AKT/mTOR signaling pathway; Inhibition; hsa04150
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: SK-Hep1 cells; Ascites; Homo sapiens (Human); CVCL_0525
• In Vitro Model: PLC/PRF/5 cells; Liver; Homo sapiens (Human); CVCL_0485
• In Vivo Model: C57BL/6J mice; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; RT/qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Increased TNFAIP8 levels in HCC cells enhanced cell survival by blocking apoptosis, rendering HCC cells more resistant to the anticancer drugs, sorafenib and regorafenib. TNFAIP8 also induced autophagy and steatosis in liver cancer cells. Consistent with these observations, TNFAIP8 blocked AKT/mTOR signaling and showed direct interaction with ATG3-ATG7 proteins.

Disease Class: Hepatic Steatosis [1]

• Resistant Disease: Hepatic Steatosis [ICD-11: DB92.Y]
• Resistant Drug: Sorafenib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: AKT/mTOR signaling pathway; Inhibition; hsa04150
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: SK-Hep1 cells; Ascites; Homo sapiens (Human); CVCL_0525
• In Vitro Model: PLC/PRF/5 cells; Liver; Homo sapiens (Human); CVCL_0485
• In Vivo Model: C57BL/6J mice; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; RT/qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Increased TNFAIP8 levels in HCC cells enhanced cell survival by blocking apoptosis, rendering HCC cells more resistant to the anticancer drugs, sorafenib and regorafenib. TNFAIP8 also induced autophagy and steatosis in liver cancer cells. Consistent with these observations, TNFAIP8 blocked AKT/mTOR signaling and showed direct interaction with ATG3-ATG7 proteins.

Disease Class: Hepatic Steatosis [1]

• Resistant Disease: Hepatic Steatosis [ICD-11: DB92.Y]
• Resistant Drug: Sorafenib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: AKT/mTOR signaling pathway; Inhibition; hsa04150
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: SK-Hep1 cells; Ascites; Homo sapiens (Human); CVCL_0525
• In Vitro Model: PLC/PRF/5 cells; Liver; Homo sapiens (Human); CVCL_0485
• In Vivo Model: C57BL/6J mice; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; RT/qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Increased TNFAIP8 levels in HCC cells enhanced cell survival by blocking apoptosis, rendering HCC cells more resistant to the anticancer drugs, sorafenib and regorafenib. TNFAIP8 also induced autophagy and steatosis in liver cancer cells. Consistent with these observations, TNFAIP8 blocked AKT/mTOR signaling and showed direct interaction with ATG3-ATG7 proteins.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 13

Nonalcoholic fatty liver disease [ICD-11: DB92]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Liver
• The Specified Disease: Nonalcoholic fatty liver disease
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.88E-02; Fold-change: 8.58E-01; Z-score: 1.11E+00

References

• Ref 1: TNFAIP8 regulates autophagy, cell steatosis, and promotes hepatocellular carcinoma cell proliferation .Cell Death Dis. 2020 Mar 9;11(3):178. doi: 10.1038/s41419-020-2369-4. 10.1038/s41419-020-2369-4