Molecule Information

General Information of the Molecule (ID: Mol00426)

• Name: Eukaryotic translation initiation factor 4E (EIF4E) ,Homo sapiens
• Synonyms: eIF-4E; eIF4E; eIF-4F 25 kDa subunit; mRNA cap-binding protein; EIF4EL1; EIF4F
• Molecule Type: Protein
• Gene Name: EIF4E
• Gene ID: 1977
• Location: chr4:98879276-98929133[-]
• Sequence:
  MATVEPETTPTPNPPTTEEEKTESNQEVANPEHYIKHPLQNRWALWFFKNDKSKTWQANL
  RLISKFDTVEDFWALYNHIQLSSNLMPGCDYSLFKDGIEPMWEDEKNKRGGRWLITLNKQ
  QRRSDLDRFWLETLLCLIGESFDDYSDDVCGAVVNVRAKGDKIAIWTTECENREAVTHIG
  RVYKERLGLPPKIVIGYQSHADTATKSGSTTKNRFVV
• Function: Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures. In addition to its role in translation initiation, also acts as a regulator of translation and stability in the cytoplasm. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression: in the complex, EIF4E mediates the binding to the mRNA cap. Component of a multiprotein complex that sequesters and represses translation of proneurogenic factors during neurogenesis. In P-bodies, component of a complex that mediates the storage of translationally inactive mRNAs in the cytoplasm and prevents their degradation. May play an important role in spermatogenesis through translational regulation of stage-specific mRNAs during germ cell development.
• Uniprot ID: IF4E_HUMAN
• Ensembl ID: ENSG00000151247
• HGNC ID: HGNC:3287

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

Docetaxel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [1]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Docetaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-141 affected the chemosensitivity of BC cells to docetaxel by directly targeting EIF4E, due to its anti-apoptotic properties. Transfection of miR-141 inhibitor could significantly promote docetaxel-induced apoptosis and change the expression of Bax and Bcl-2. However, when the BC cells were transfected with siRNA-EIF4E, the data showed opposite results. It suggested that EIF4E is partly responsible for the miR-141-induced apoptosis which is related to the mitochondrial apoptosis pathway. In the previous studies, antisense Bcl-2 treatment (+) sensitivity to tamoxifen in HER2-positive cells in tamoxifen-resistant BC cells.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Non-small cell lung cancer [2]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Sensitive Drug: Docetaxel
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EIF4E/VEGF/c-Myc/Bax signaling pathway; Activation; hsa04066
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: H2009 cells; Lung; Homo sapiens (Human); CVCL_1514
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTT assay; Annexin V-FITC Apoptosis assay
• Mechanism Description: Down-regulation of miR141 suppressed cell proliferation, induced cell death and increased caspase-3 activity in H1299 or H2009/docetaxel cells. Down-regulation of miR141 also increased the protein expression of EIF4E, VEGF, c-Myc and Bax in H1299 or H2009/docetaxel cells.

Fluorouracil

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Hepatocellular carcinoma [3]

• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Resistant Drug: Fluorouracil
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: BEL-7402 cells; Liver; Homo sapiens (Human); CVCL_5492
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: SMMC7721 cells; Uterus; Homo sapiens (Human); CVCL_0534
• In Vitro Model: L02 cells; Liver; Homo sapiens (Human); CVCL_6926
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR503 inhibits proliferation making human hepatocellular carcinoma cells susceptible to 5 fluorouracil by targeting EIF4E.

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: 3.85E-01; Fold-change: -3.27E-02; Z-score: -5.57E-02
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.85E-01; Fold-change: -9.11E-02; Z-score: -1.88E-01
• The Expression Level of Disease Section Compare with the Other Disease Section: p-value: 3.90E-01; Fold-change: -3.25E-01; Z-score: -7.64E-01

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: 2.01E-05; Fold-change: -2.11E-01; Z-score: -4.74E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 4.19E-01; Fold-change: 3.90E-02; Z-score: 8.71E-02

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: 1.16E-05; Fold-change: 3.14E-01; Z-score: 4.01E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.33E-02; Fold-change: 1.68E-01; Z-score: 2.11E-01

References

• Ref 1: miR-141 confers docetaxel chemoresistance of breast cancer cells via regulation of EIF4E expression. Oncol Rep. 2015 May;33(5):2504-12. doi: 10.3892/or.2015.3866. Epub 2015 Mar 18.
• Ref 2: miR-141 regulation of EIF4E expression affects docetaxel chemoresistance of non-small cell lung cancer. Oncol Rep. 2017 Jan;37(1):608-616. doi: 10.3892/or.2016.5214. Epub 2016 Nov 2.
• Ref 3: miR-503 inhibits proliferation making human hepatocellular carcinoma cells susceptible to 5 fluorouracil by targeting EIF4E. Oncol Rep. 2017 Jan;37(1):563-570. doi: 10.3892/or.2016.5220. Epub 2016 Nov 7.