Molecule Information

General Information of the Molecule (ID: Mol00610)

• Name: DNA-directed RNA polymerase I subunit RPA12 (RPA12) ,Homo sapiens
• Synonyms: DNA-directed RNA polymerase I subunit H; Zinc ribbon domain-containing protein 1; RPA12; ZNRD1
• Molecule Type: Protein
• Gene Name: POLR1H
• Gene ID: 30834
• Location: chr6:30058899-30064909[+]
• Sequence:
  MSVMDLANTCSSFQSDLDFCSDCGSVLPLPGAQDTVTCIRCGFNINVRDFEGKVVKTSVV
  FHQLGTAMPMSVEEGPECQGPVVDRRCPRCGHEGMAYHTRQMRSADEGQTVFYTCTNCKF
  QEKEDS
• Function: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase I which synthesizes ribosomal RNA precursors.
• Uniprot ID: RPA12_HUMAN
• Ensembl ID: ENSG00000066379
• HGNC ID: HGNC:13182

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) 4 drug(s) in total

Cisplatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Gastric cancer [1]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1.

Doxorubicin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Gastric cancer [1]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1.

Fluorouracil

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Gastric cancer [1]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Sensitive Drug: Fluorouracil
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1.

Vincristine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Gastric cancer [1]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Sensitive Drug: Vincristine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC7901/VCR cells; Gastric; Homo sapiens (Human); CVCL_VU58
• In Vitro Model: SGC7901/ADR cells; Gastric; Homo sapiens (Human); CVCL_VU57
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3'-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1.

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: 2.70E-01; Fold-change: 8.24E-01; Z-score: 9.64E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 3.88E-02; Fold-change: 1.84E-01; Z-score: 6.08E-01

References

• Ref 1: miR-508-5p regulates multidrug resistance of gastric cancer by targeting ABCB1 and ZNRD1. Oncogene. 2014 Jun 19;33(25):3267-76. doi: 10.1038/onc.2013.297. Epub 2013 Jul 29.