Molecule Information

General Information of the Molecule (ID: Mol00087)

• Name: Heme oxygenase 1 (HMOX1) ,Homo sapiens
• Synonyms: HO-1; HO; HO1
• Molecule Type: Protein
• Gene Name: HMOX1
• Gene ID: 3162
• Location: chr22:35380361-35394214[+]
• Sequence:
  MERPQPDSMPQDLSEALKEATKEVHTQAENAEFMRNFQKGQVTRDGFKLVMASLYHIYVA
  LEEEIERNKESPVFAPVYFPEELHRKAALEQDLAFWYGPRWQEVIPYTPAMQRYVKRLHE
  VGRTEPELLVAHAYTRYLGDLSGGQVLKKIAQKALDLPSSGEGLAFFTFPNIASATKFKQ
  LYRSRMNSLEMTPAVRQRVIEEAKTAFLLNIQLFEELQELLTHDTKDQSPSRAPGLRQRA
  SNKVQDSAPVETPRGKPPLNTRSQAPLLRWVLTLSFLVATVAVGLYAM
• Function: Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed. Exhibits cytoprotective effects since excess of free heme sensitizes cells to undergo apoptosis.
• Uniprot ID: HMOX1_HUMAN
• Ensembl ID: ENSG00000100292
• HGNC ID: HGNC:5013

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) 2 drug(s) in total

Arsenic trioxide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Lung cancer [1]

• Resistant Disease: Lung cancer [ICD-11: 2C25.5]
• Resistant Drug: Arsenic trioxide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Nrf2 signaling pathway; Activation; hsa05208
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: MTT Assay
• Mechanism Description: miR155 mediates arsenic trioxide resistance by activating Nrf2 and suppressing apoptosis in lung cancer cells. miR155 mediated ATO resistance by upregulating the Nrf2 signaling pathway, but downregulating cellular apoptosis in lung cancer cells.

Conivaptan

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Solid tumour/cancer [2]

• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Resistant Drug: Conivaptan
• Molecule Alteration: Function; Inhibition
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ATCC 293T cells; Fetal kidney; Homo sapiens (Human); CVCL_0063
• Experiment for Molecule Alteration: Resazurin assay
• Mechanism Description: HMOX1, PRKCA, and NEIL2 contribute to anthracycline resistance within the more complex MDR phenotype, while P-glycoprotein/ABCB1 overexpression causes not only anthracycline resistance but also resistance to other anticancer drug classes. Conivaptan has the potential to be used as the dual inhibitor of HMOX1 and PRKCA, whereas bexarotene has the potential as an HMOX1 inhibitor and desloratadine as a PRKCA inhibitor.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Lung cancer [ICD-11: 2C25]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Lung
• The Specified Disease: Lung cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.25E-17; Fold-change: -4.73E-01; Z-score: -5.23E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 2.29E-10; Fold-change: -7.41E-01; Z-score: -6.45E-01

References

• Ref 1: miR-155 mediates arsenic trioxide resistance by activating Nrf2 and suppressing apoptosis in lung cancer cells. Sci Rep. 2017 Sep 22;7(1):12155. doi: 10.1038/s41598-017-06061-x.
• Ref 2: Identification of Novel Anthracycline Resistance Genes and Their Inhibitors .Pharmaceuticals (Basel). 2021 Oct 16;14(10):1051. doi: 10.3390/ph14101051. 10.3390/ph14101051