Molecule Information

General Information of the Molecule (ID: Mol00639)

• Name: Zinc finger protein SNAI2 (SNAI2) ,Homo sapiens
• Synonyms: Neural crest transcription factor Slug; Protein snail homolog 2; SLUG; SLUGH
• Molecule Type: Protein
• Gene Name: SNAI2
• Gene ID: 6591
• Location: chr8:48917598-48921740[-]
• Sequence:
  MPRSFLVKKHFNASKKPNYSELDTHTVIISPYLYESYSMPVIPQPEILSSGAYSPITVWT
  TAAPFHAQLPNGLSPLSGYSSSLGRVSPPPPSDTSSKDHSGSESPISDEEERLQSKLSDP
  HAIEAEKFQCNLCNKTYSTFSGLAKHKQLHCDAQSRKSFSCKYCDKEYVSLGALKMHIRT
  HTLPCVCKICGKAFSRPWLLQGHIRTHTGEKPFSCPHCNRAFADRSNLRAHLQTHSDVKK
  YQCKNCSKTFSRMSLLHKHEESGCCVAH
• Function: Transcriptional repressor that modulates both activator-dependent and basal transcription. Involved in the generation and migration of neural crest cells. Plays a role in mediating RAF1-induced transcriptional repression of the TJ protein, occludin (OCLN) and subsequent oncogenic transformation of epithelial cells (By similarity). Represses BRCA2 expression by binding to its E2-box-containing silencer and recruiting CTBP1 and HDAC1 in breast cells. In epidermal keratinocytes, binds to the E-box in ITGA3 promoter and represses its transcription. Involved in the regulation of ITGB1 and ITGB4 expression and cell adhesion and proliferation in epidermal keratinocytes. Binds to E-box2 domain of BSG and activates its expression during TGFB1-induced epithelial-mesenchymal transition (EMT) in hepatocytes. Represses E-Cadherin/CDH1 transcription via E-box elements. Involved in osteoblast maturation. Binds to RUNX2 and SOC9 promoters and may act as a positive and negative transcription regulator, respectively, in osteoblasts. Binds to CXCL12 promoter via E-box regions in mesenchymal stem cells and osteoblasts. Plays an essential role in TWIST1-induced EMT and its ability to promote invasion and metastasis.
• Uniprot ID: SNAI2_HUMAN
• Ensembl ID: ENSG00000019549
• HGNC ID: HGNC:11094

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

Type(s) of Resistant Mechanism of This Molecule

  RTDM: Regulation by the Disease Microenvironment

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 5 drug(s) in total

Cisplatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Non-small cell lung cancer [1]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell colony; Inhibition; hsa05200
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: MAPK/Slug signaling pathway; Regulation; hsa04010
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: SPC-A1 cells; Lung; Homo sapiens (Human); CVCL_6955
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: LncRNA NNT-AS1 is a major mediator of cisplatin chemoresistance in non-small cell lung cancer through MAPk/Slug pathway.

Fluorouracil

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Disease Class: Colorectal cancer [2]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Sensitive Drug: Fluorouracil
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: HT29 Cells; Colon; Homo sapiens (Human); CVCL_A8EZ
• In Vitro Model: DLD1 cells; Colon; Homo sapiens (Human); CVCL_0248
• In Vitro Model: SW620 cells; Colon; Homo sapiens (Human); CVCL_0547
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: LS174T cells; Colon; Homo sapiens (Human); CVCL_1384
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Trypan blue assay; Sulforhodamine B assay
• Mechanism Description: Inhibition of SNAI2 directly with short hairpin sequence for SNAI2 and miR145 replacement therapy both decreased vimentin expression and increased in vitro 5FU sensitivity.

Gefitinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Non-small cell lung cancer [3]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Sensitive Drug: Gefitinib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• Experiment for Molecule Alteration: Western blot analysis; Luciferase Assay
• Experiment for Drug Resistance: CCK8 assay; Annexin V-FITC Apoptosis assay
• Mechanism Description: miR124 decreased SNAI2 and STAT3 expression by directly targeting their 3'UTRs, miR124 contributes to gefitinib and EMT by directly targeting S.I2 and STAT3. Over-expression of miR124 re-sensitized gefitinib-resistant cell lines to gefitinib.

Gemcitabine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Pancreatic cancer [4]

• Sensitive Disease: Pancreatic cancer [ICD-11: 2C10.3]
• Sensitive Drug: Gemcitabine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Slug/PUMA signaling pathway; Regulation; hsa04390
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• Experiment for Molecule Alteration: RT-PCR; Western blot analysis
• Experiment for Drug Resistance: Flow Cytometric Analysis, MTT assay; TUNEL staining
• Mechanism Description: miR34 increases in vitro PANC-1 cell sensitivity to gemcitabine via targeting Slug/PUMA. miR34 enhances sensitization against gemcitabine-mediated apoptosis through the down-regulation of Slug expression, and up-regulation of Slug-dependent PUMA expression.

Imatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Glioblastoma [5]

• Resistant Disease: Glioblastoma [ICD-11: 2A00.02]
• Resistant Drug: Imatinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• In Vitro Model: U251 cells; Brain; Homo sapiens (Human); CVCL_0021
• In Vitro Model: U87 cells; Brain; Homo sapiens (Human); CVCL_0022
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: SNAI2 is a direct target of miR-203 and that miR-203-mediated inhibition of SNAI2 is dependent on a conversed motif in the 3'-UTR of SNAI2. Recent independent studies have shown that overexpression of SNAI2 alters cell invasion, motility, chemoresistance, metastasis and poor prognosis in several human cancers. As a member of the snail family of transcription factors, SNAI2 can repress E-cadherin transcription and induce EMT directly. Therefore, SNAI2 overexpression due to reduction of miR-203 may result in EMT and chemoresistance in GBM via these pathways. Additionally, miR-203 may relieve E-cadherin from transcriptional repression by targeting SNAI2 signaling. Nevertheless, because one single miRNA might have multiple targets, judicious considerations are essential for identi cation of the main functional targets.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Brain cancer [ICD-11: 2A00]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Nervous tissue
• The Specified Disease: Brain cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.37E-107; Fold-change: 1.53E+00; Z-score: 1.86E+00
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.46E-01; Fold-change: 2.15E+00; Z-score: 2.54E+00
• The Studied Tissue: White matter
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.99E-03; Fold-change: 1.12E+00; Z-score: 1.26E+00
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Neuroectodermal tumor
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.87E-07; Fold-change: 2.58E+00; Z-score: 3.54E+00

Pancreatic cancer [ICD-11: 2C10]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Pancreas
• The Specified Disease: Pancreatic cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.03E-02; Fold-change: 7.83E-01; Z-score: 1.25E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 5.29E-04; Fold-change: 1.52E+00; Z-score: 1.02E+00

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: 4.63E-05; Fold-change: 8.73E-02; Z-score: 1.20E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 5.94E-01; Fold-change: -1.81E-01; Z-score: -2.32E-01

References

• Ref 1: LncRNA NNT-AS1 is a major mediator of cisplatin chemoresistance in non-small cell lung cancer through MAPK/Slug pathway. Eur Rev Med Pharmacol Sci. 2018 Aug;22(15):4879-4887. doi: 10.26355/eurrev_201808_15624.
• Ref 2: SNAI2 modulates colorectal cancer 5-fluorouracil sensitivity through miR145 repression. Mol Cancer Ther. 2014 Nov;13(11):2713-26. doi: 10.1158/1535-7163.MCT-14-0207. Epub 2014 Sep 23.
• Ref 3: miR-124 modulates gefitinib resistance through SNAI2 and STAT3 in non-small cell lung cancer. J Huazhong Univ Sci Technolog Med Sci. 2016 Dec;36(6):839-845. doi: 10.1007/s11596-016-1672-x. Epub 2016 Dec 7.
• Ref 4: miR-34 increases in vitro PANC-1 cell sensitivity to gemcitabine via targeting Slug/PUMA. Cancer Biomark. 2018;21(4):755-762. doi: 10.3233/CBM-170289.
• Ref 5: MiR-203 downregulation is responsible for chemoresistance in human glioblastoma by promoting epithelial-mesenchymal transition via SNAI2. Oncotarget. 2015 Apr 20;6(11):8914-28. doi: 10.18632/oncotarget.3563.