Molecule Information

General Information of the Molecule (ID: Mol00689)

• Name: Twist-related protein 1 (TWST1) ,Homo sapiens
• Synonyms: Class A basic helix-loop-helix protein 38; bHLHa38; H-twist; BHLHA38; TWIST
• Molecule Type: Protein
• Gene Name: TWIST1
• Gene ID: 7291
• Location: chr7:19020991-19117636[-]
• Sequence:
  MMQDVSSSPVSPADDSLSNSEEEPDRQQPPSGKRGGRKRRSSRRSAGGGAGPGGAAGGGV
  GGGDEPGSPAQGKRGKKSAGCGGGGGAGGGGGSSSGGGSPQSYEELQTQRVMANVRERQR
  TQSLNEAFAALRKIIPTLPSDKLSKIQTLKLAARYIDFLYQVLQSDELDSKMASCSYVAH
  ERLSYAFSVWRMEGAWSMSASH
• Function: Acts as a transcriptional regulator. Inhibits myogenesis by sequestrating E proteins, inhibiting trans-activation by MEF2, and inhibiting DNA-binding by MYOD1 through physical interaction. This interaction probably involves the basic domains of both proteins. Also represses expression of proinflammatory cytokines such as TNFA and IL1B. Regulates cranial suture patterning and fusion. Activates transcription as a heterodimer with E proteins. Regulates gene expression differentially, depending on dimer composition. Homodimers induce expression of FGFR2 and POSTN while heterodimers repress FGFR2 and POSTN expression and induce THBS1 expression. Heterodimerization is also required for osteoblast differentiation. Represses the activity of the circadian transcriptional activator: NPAS2-ARNTL/BMAL1 heterodimer (By similarity).
• Uniprot ID: TWST1_HUMAN
• Ensembl ID: ENSG00000122691
• HGNC ID: HGNC:12428

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

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Tongue squamous cell carcinoma [1]

• Resistant Disease: Tongue squamous cell carcinoma [ICD-11: 2B62.1]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: JNk signaling pathway; Activation; hsa04010
• In Vitro Model: Tca8113 cells; Tongue; Homo sapiens (Human); CVCL_6851
• In Vitro Model: SCC4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Overexpression of miR-23a in both SCC-4 and Tca8113 cells markedly increased Twist expression, c-Jun N-terminal kinase (JNk) activity and the half maximal inhibitory concentration (IC50) of cisplain, and decreased cisplatin-induced apoptosis, all of which was abolished by knockdown of Twist or selective JNk inhibitor SP600125. On the other hand, knockdown of miR-23a significantly decreased Twist expression, JNk activity and IC50 of cisplain, and increased cisplatin-induced apoptosis, all of which was completely reversed by overexpression of Twist. The present study for the first time demonstrates that miR-23a promotes cisplatin chemoresistance and protects cisplatin-induced apoptosis in TSCC cells through inducing Twist expression by a JNk-dependent mechanism.

Disease Class: Osteosarcoma [2]

• Resistant Disease: Osteosarcoma [ICD-11: 2B51.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: MG63 cells; Bone marrow; Homo sapiens (Human); CVCL_0426
• In Vitro Model: SAOS-2 cells; Bone marrow; Homo sapiens (Human); CVCL_0548
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: TUNEL assay
• Mechanism Description: miR-33a is up-regulated in chemoresistant OS and that the miR-33a level is negatively correlated with the TWIST protein level in OS. miR-33a promotes OS cell resistance to cisplatin by down-regulating TWIST.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Tongue squamous cell carcinoma [3]

• Sensitive Disease: Tongue squamous cell carcinoma [ICD-11: 2B62.1]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: miR181a-Twist1 signaling pathway; Regulation; hsa05206
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: SCC15 cells; Tongue; Homo sapiens (Human); CVCL_1681
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Cisplatin chemoresistance induced EMT, enhanced metastatic potential and down-regulated miR-181a in TSCC cells, miR-181a directly targeted Twist1 and then reversed chemoresistance and EMT in TSCC cells, miR-181a-Twist1 pathway may play an important role in the development of cisplatin-chemoresistance.

Epirubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [4]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Epirubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: SUM1315 cells; Breast; Homo sapiens (Human); CVCL_5589
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR; luciferase reporter assay; Western blot analysis
• Experiment for Drug Resistance: CCK8 toxicity assay
• Mechanism Description: Twist1 is a target protein of miR-129-5p and positively regulates by NONHSAT101069 in BC cells. and it stimulates epirubicin resistance, migration, invasion, and EMT progression of BC cells.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 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: 3.29E-36; Fold-change: -1.44E+00; Z-score: -1.10E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 6.55E-06; Fold-change: -1.21E+00; Z-score: -9.13E-01

References

• Ref 1: miR-23a promotes cisplatin chemoresistance and protects against cisplatin-induced apoptosis in tongue squamous cell carcinoma cells through Twist. Oncol Rep. 2015 Feb;33(2):942-50. doi: 10.3892/or.2014.3664. Epub 2014 Dec 10.
• Ref 2: miR-33a is up-regulated in chemoresistant osteosarcoma and promotes osteosarcoma cell resistance to cisplatin by down-regulating TWIST. J Exp Clin Cancer Res. 2014 Jan 27;33(1):12. doi: 10.1186/1756-9966-33-12.
• Ref 3: miR-181a-Twist1 pathway in the chemoresistance of tongue squamous cell carcinoma. Biochem Biophys Res Commun. 2013 Nov 15;441(2):364-70. doi: 10.1016/j.bbrc.2013.10.051. Epub 2013 Oct 19.
• Ref 4: Long non-coding RNA NONHSAT101069 promotes epirubicin resistance, migration, and invasion of breast cancer cells through NONHSAT101069/miR-129-5p/Twist1 axis. Oncogene. 2019 Nov;38(47):7216-7233. doi: 10.1038/s41388-019-0904-5. Epub 2019 Aug 23.