Molecule Information

General Information of the Molecule (ID: Mol00642)

• Name: Superoxide dismutase Mn (SODM) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: SOD2
• Gene ID: 6648
• Location: chr6:159669069-159762529[-]
• Sequence:
  MLSRAVCGTSRQLAPVLGYLGSRQKHSLPDLPYDYGALEPHINAQIMQLHHSKHHAAYVN
  NLNVTEEKYQEALAKGDVTAQIALQPALKFNGGGHINHSIFWTNLSPNGGGEPKGELLEA
  IKRDFGSFDKFKEKLTAASVGVQGSGWGWLGFNKERGHLQIAACPNQDPLQGTTGLIPLL
  GIDVWEHAYYLQYKNVRPDYLKAIWNVINWENVTERYMACKK
• Function: Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.
• Uniprot ID: SODM_HUMAN
• Ensembl ID: ENSG00000112096
• HGNC ID: HGNC:11180

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

Type(s) of Resistant Mechanism of This Molecule

  DISM: Drug Inactivation by Structure Modification

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

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

Paclitaxel

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Ovarian cancer [1]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Sensitive Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: miR146a/SOD2/ROS signaling pathway; Regulation; hsa05206
• In Vitro Model: HEY cells; Ovary; Homo sapiens (Human); CVCL_0297
• In Vitro Model: OVCAR3 cells; Ovary; Homo sapiens (Human); CVCL_0465
• In Vitro Model: CAOV3 cells; Ovary; Homo sapiens (Human); CVCL_0201
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; TUNEL Assay
• Mechanism Description: miR146a downregulates the expression of SOD2 and enhances ROS generation, leading to increased apoptosis, inhibition of proliferation, and enhanced sensitivity to chemotherapy.

Disease Class: Epithelial ovarian cancer [1]

• Sensitive Disease: Epithelial ovarian cancer [ICD-11: 2B5D.0]
• Sensitive Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: miR146a/SOD2/ROS signaling pathway; Regulation; hsa05206
• In Vitro Model: Huh-7 cells; Liver; Homo sapiens (Human); CVCL_0336
• 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: PLC cells; Liver; Homo sapiens (Human); CVCL_0485
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; CCK8 assay
• Mechanism Description: miR-146a as a potential tumor suppressor in patients with EOC. miR-146a downregulates expression of SOD2 and enhances ROS generation, leading to increased apoptosis, inhibition of proliferation, and (+) sensitivity to chemotherapy.

Clinical Trial Drug(s) 1 drug(s) in total

Betulinic acid

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Hepatocellular carcinoma [2]

• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Resistant Drug: Betulinic acid
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: p53/p66shc/miR21-Sod2 signaling pathway; Regulation; hsa05206
• In Vitro Model: Huh-7 cells; Liver; Homo sapiens (Human); CVCL_0336
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: SMMC7721 cells; Uterus; Homo sapiens (Human); CVCL_0534
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; TUNEL assay; Promega
• Mechanism Description: p53 is responsible for the anti-tumor effect of betulinic acid through up-regulation of p66(shc) and miR-21 and down-regulation of Sod2 expression, leading to mitochondrial ROS accumulation and apoptosis.

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

PLX51107

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Uveal melanoma [3]

• Sensitive Disease: Uveal melanoma [ICD-11: 2D0Y.0]
• Sensitive Drug: PLX51107
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: NF-kappaB signaling pathway; Inhibition; hsa04064
• In Vitro Model: Omm1.3 cells; Skin; Homo sapiens (Human); N.A.
• In Vitro Model: 92.1 cells; Peripheral blood; Homo sapiens (Human); N.A.
• In Vitro Model: UM004 cells; Skin; Homo sapiens (Human); N.A.
• In Vitro Model: Omm1 cells; Kidney; Homo sapiens (Human); CVCL_6939
• In Vivo Model: Athymic nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR; Western blotting assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Both assays showed higher expression of these genes(REL, RELB, CEBPD, SOD2) at the mRNA and protein level in the resistant cells compared with their parental counterpart. Furthermore, NF-kappa-B activity was increased in the resistant cells compared with parental, and it could be inhibited by PTL.Inhibition of NF-kappa-B-dependent signaling enhances sensitivity and overcomes resistance to BET inhibition in uveal melanoma.

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: 7.96E-07; Fold-change: -8.27E-01; Z-score: -9.39E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 5.74E-02; Fold-change: 2.15E-01; Z-score: 2.21E-01
• The Expression Level of Disease Section Compare with the Other Disease Section: p-value: 3.71E-02; Fold-change: -7.64E-01; Z-score: -1.40E+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: 1.62E-01; Fold-change: -4.39E-01; Z-score: -3.52E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.07E-02; Fold-change: 9.42E-01; Z-score: 1.02E+00

References

• Ref 1: miR-146a Inhibits Proliferation and Enhances Chemosensitivity in Epithelial Ovarian Cancer via Reduction of SOD2. Oncol Res. 2016;23(6):275-82. doi: 10.3727/096504016X14562725373798.
• Ref 2: p53-p66(shc)/miR-21-Sod2 signaling is critical for the inhibitory effect of betulinic acid on hepatocellular carcinoma. Toxicol Lett. 2015 Nov 4;238(3):1-10. doi: 10.1016/j.toxlet.2015.07.016. Epub 2015 Jul 26.
• Ref 3: Inhibition of NF-kB-Dependent Signaling Enhances Sensitivity and Overcomes Resistance to BET Inhibition in Uveal Melanoma .Cancer Res. 2019 May 1;79(9):2415-2425. doi: 10.1158/0008-5472.CAN-18-3177. Epub 2019 Mar 18. 10.1158/0008-5472.CAN-18-3177