Molecule Information

General Information of the Molecule (ID: Mol00585)

• Name: DNA repair protein RAD51 homolog 1 (RAD51) ,Homo sapiens
• Synonyms: HsRAD51; hRAD51; RAD51 homolog A; RAD51A; RECA
• Molecule Type: Protein
• Gene Name: RAD51
• Gene ID: 5888
• Location: chr15:40694774-40732340[+]
• Sequence:
  MAMQMQLEANADTSVEEESFGPQPISRLEQCGINANDVKKLEEAGFHTVEAVAYAPKKEL
  INIKGISEAKADKILAEAAKLVPMGFTTATEFHQRRSEIIQITTGSKELDKLLQGGIETG
  SITEMFGEFRTGKTQICHTLAVTCQLPIDRGGGEGKAMYIDTEGTFRPERLLAVAERYGL
  SGSDVLDNVAYARAFNTDHQTQLLYQASAMMVESRYALLIVDSATALYRTDYSGRGELSA
  RQMHLARFLRMLLRLADEFGVAVVITNQVVAQVDGAAMFAADPKKPIGGNIIAHASTTRL
  YLRKGRGETRICKIYDSPCLPEAEAMFAINADGVGDAKD
• Function: Plays an important role in homologous strand exchange, a key step in DNA repair through homologous recombination (HR). Binds to single and double-stranded DNA and exhibits DNA-dependent ATPase activity. Catalyzes the recognition of homology and strand exchange between homologous DNA partners to form a joint molecule between a processed DNA break and the repair template. Binds to single-stranded DNA in an ATP-dependent manner to form nucleoprotein filaments which are essential for the homology search and strand exchange. Part of a PALB2-scaffolded HR complex containing BRCA2 and RAD51C and which is thought to play a role in DNA repair by HR. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51C and XRCC3. Also involved in interstrand cross-link repair.
• Uniprot ID: RAD51_HUMAN
• Ensembl ID: ENSG00000051180
• HGNC ID: HGNC:9817

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) 3 drug(s) in total

Cisplatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Ovarian serous carcinoma [1]

• Sensitive Disease: Ovarian serous carcinoma [ICD-11: 2C73.2]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: CDK4/6-FOXM1 signaling pathway; Regulation; hsa04218
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Homologous recombination-mediated repair pathway; Inhibition; hsa03440
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: Hey A8 cells; Ovary; Homo sapiens (Human); CVCL_8878
• In Vitro Model: OVCA433 cells; Ovary; Homo sapiens (Human); CVCL_0475
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-506 overexpression sensitized ovarian cancer cells to cisplatin or to a commercially available PARP inhibitor (olaparib) due to miR-506 overexpression decreasing RAD51 levels and homologous recombination efficiency.

Disease Class: Osteosarcoma [2], [3]

• Sensitive Disease: Osteosarcoma [ICD-11: 2B51.0]
• Sensitive Drug: Cisplatin
• 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
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Survival assay/crystal violet staining assay
• Mechanism Description: miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization. And overexpression of miR-96 in human cancer cells reduces the levels of RAD51 and REV1 and impacts the cellular response to agents that cause DNA damage.

Disease Class: Breast adenocarcinoma [2], [3]

• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Sensitive Drug: Cisplatin
• 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
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Survival assay/crystal violet staining assay
• Mechanism Description: miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization. And overexpression of miR-96 in human cancer cells reduces the levels of RAD51 and REV1 and impacts the cellular response to agents that cause DNA damage.

Disease Class: HPV-related endocervical adenocarcinoma [2], [3]

• Sensitive Disease: HPV-related endocervical adenocarcinoma [ICD-11: 2E67.1]
• Sensitive Drug: Cisplatin
• 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
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Survival assay/crystal violet staining assay
• Mechanism Description: miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization. And overexpression of miR-96 in human cancer cells reduces the levels of RAD51 and REV1 and impacts the cellular response to agents that cause DNA damage.

Disease Class: Lung large cell carcinoma [2], [3]

• Sensitive Disease: Lung large cell carcinoma [ICD-11: 2C25.4]
• Sensitive Drug: Cisplatin
• 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
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Survival assay/crystal violet staining assay
• Mechanism Description: miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization. And overexpression of miR-96 in human cancer cells reduces the levels of RAD51 and REV1 and impacts the cellular response to agents that cause DNA damage.

Etoposide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Osteosarcoma [3]

• Sensitive Disease: Osteosarcoma [ICD-11: 2B51.0]
• Sensitive Drug: Etoposide
• 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
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Survival assay/crystal violet staining assay
• Mechanism Description: miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.

Disease Class: Breast cancer [3]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Sensitive Drug: Etoposide
• 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
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Survival assay/crystal violet staining assay
• Mechanism Description: miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.

Disease Class: Cervical cancer [3]

• Sensitive Disease: Cervical cancer [ICD-11: 2C77.0]
• Sensitive Drug: Etoposide
• 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
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Survival assay/crystal violet staining assay
• Mechanism Description: miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.

Disease Class: Lung cancer [3]

• Sensitive Disease: Lung cancer [ICD-11: 2C25.5]
• Sensitive Drug: Etoposide
• 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
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Survival assay/crystal violet staining assay
• Mechanism Description: miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.

Disease Class: Ovarian cancer [3]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Sensitive Drug: Etoposide
• 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
• In Vitro Model: PEO1 C4-2 cells; Ovary; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Survival assay/crystal violet staining assay
• Mechanism Description: miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.

Olaparib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Ovarian serous carcinoma [1]

• Sensitive Disease: Ovarian serous carcinoma [ICD-11: 2C73.2]
• Sensitive Drug: Olaparib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: CDK4/6-FOXM1 signaling pathway; Regulation; hsa04218
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Homologous recombination-mediated repair pathway; Inhibition; hsa03440
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: Hey A8 cells; Ovary; Homo sapiens (Human); CVCL_8878
• In Vitro Model: OVCA433 cells; Ovary; Homo sapiens (Human); CVCL_0475
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-506 overexpression sensitized ovarian cancer cells to cisplatin or to a commercially available PARP inhibitor (olaparib) due to miR-506 overexpression decreasing RAD51 levels and homologous recombination efficiency.

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

Camptothecin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Osteosarcoma [3]

• Sensitive Disease: Osteosarcoma [ICD-11: 2B51.0]
• Sensitive Drug: Camptothecin
• 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
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Survival assay/crystal violet staining assay
• Mechanism Description: miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.

Disease Class: Breast cancer [3]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Sensitive Drug: Camptothecin
• 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
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Survival assay/crystal violet staining assay
• Mechanism Description: miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.

Disease Class: Cervical cancer [3]

• Sensitive Disease: Cervical cancer [ICD-11: 2C77.0]
• Sensitive Drug: Camptothecin
• 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
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Survival assay/crystal violet staining assay
• Mechanism Description: miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.

Disease Class: Lung cancer [3]

• Sensitive Disease: Lung cancer [ICD-11: 2C25.5]
• Sensitive Drug: Camptothecin
• 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
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Survival assay/crystal violet staining assay
• Mechanism Description: miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.

Disease Class: Ovarian cancer [3]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Sensitive Drug: Camptothecin
• 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
• In Vitro Model: PEO1 C4-2 cells; Ovary; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Survival assay/crystal violet staining assay
• Mechanism Description: miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.

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: 4.40E-140; Fold-change: 7.37E-01; Z-score: 3.40E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.70E-103; Fold-change: 7.86E-01; Z-score: 3.69E+00

Breast cancer [ICD-11: 2C60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Breast tissue
• The Specified Disease: Breast cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.23E-160; Fold-change: 6.01E-01; Z-score: 2.85E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.54E-15; Fold-change: 4.85E-01; Z-score: 1.55E+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: 8.05E-07; Fold-change: 8.96E-01; Z-score: 4.08E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 8.93E-01; Fold-change: 4.95E-01; Z-score: 5.98E-01

Cervical cancer [ICD-11: 2C77]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Cervix uteri
• The Specified Disease: Cervical cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.39E-07; Fold-change: 5.69E-01; Z-score: 1.98E+00

References

• Ref 1: Augmentation of response to chemotherapy by microRNA-506 through regulation of RAD51 in serous ovarian cancers. J Natl Cancer Inst. 2015 May 20;107(7):djv108. doi: 10.1093/jnci/djv108. Print 2015 Jul.
• Ref 2: MiR-96 downregulates REV1 and RAD51 to promote cellular sensitivity to cisplatin and PARP inhibition. Cancer Res. 2012 Aug 15;72(16):4037-46. doi: 10.1158/0008-5472.CAN-12-0103. Epub 2012 Jul 3.
• Ref 3: Systematic screen identifies miRNAs that target RAD51 and RAD51D to enhance chemosensitivity. Mol Cancer Res. 2013 Dec;11(12):1564-73. doi: 10.1158/1541-7786.MCR-13-0292. Epub 2013 Oct 2.