Molecule Information

General Information of the Molecule (ID: Mol01297)

• Name: Taurine up-regulated 1 (TUG1) ,Homo sapiens
• Synonyms: TUG1
• Molecule Type: LncRNA
• Gene Name: HCN, LINC00047, MALAT-1, NCRNA00047, NEAT2, PRO1073, mascRNA
• Gene ID: 55000
• Location: chr22:30969245-30979395[+]
• Ensembl ID: ENSG00000253352
• HGNC ID: HGNC:26066

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

Type(s) of Resistant Mechanism of This Molecule

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

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

Gemcitabine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0] [1]

• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Resistant Drug: Gemcitabine
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic adenocarcinoma
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 9.57E-23; Fold-change: 5.17E-01; Z-score: 1.06E+01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell colony; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: ERK signaling pathway; Activation; hsa04210
• In Vitro Model: BxPC-3 cells; Pancreas; Homo sapiens (Human); CVCL_0186
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• In Vitro Model: SW1990 cells; Pancreas; Homo sapiens (Human); CVCL_1723
• In Vitro Model: PANC-28 cells; Pancreatic; Homo sapiens (Human); CVCL_3917
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: TUG1 promoted the viability of PDAC cells and enhanced its resistance of gemcitabine and overexpression of TUG1 increased ERk phosphorylation.

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Esophageal squamous cell carcinoma [ICD-11: 2B70.3] [2]

• Resistant Disease: Esophageal squamous cell carcinoma [ICD-11: 2B70.3]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Esophageal cancer [ICD-11: 2B70]
• The Specified Disease: Esophageal carcinoma
• The Studied Tissue: Esophagus
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.51E-16; Fold-change: 4.24E-01; Z-score: 8.85E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: TE-1 cells; Esophagus; Homo sapiens (Human); CVCL_1759
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: TUG1 promoted cell resistance to DDP, at least in part, through upregulating Nrf2.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Breast cancer [ICD-11: 2C60.3] [3]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: Wnt signaling pathway; Inhibition; hsa04310
• 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
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: BT549 cells; Breast; Homo sapiens (Human); CVCL_1092
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: LncRNA TUG1 sensitized triple negative breast cancer to cisplatin by upregulating NLk expression via sponging miR-197.

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] [4]

• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: HL60 cells; Peripheral blood; Homo sapiens (Human); CVCL_0002
• In Vitro Model: HS-5 cells; Bone marrow; Homo sapiens (Human); CVCL_3720
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: TUG1 epigenetically suppressed miR-34a expression by recruiting EZH2 to the promoter region of miR-34a and increasing H3k27me3 level to confer adriamycin resistance in acute myeloid leukemia.

Methotrexate

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Colorectal cancer [ICD-11: 2B91.1] [5]

• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Resistant Drug: Methotrexate
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HCT-8 cells; Colon; Homo sapiens (Human); CVCL_2478
• In Vitro Model: HT-29-R cells; Colon; Homo sapiens (Human); CVCL_6834
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis
• Mechanism Description: TUG1 mediates methotrexate resistance in colorectal cancer via miR186/CPEB2 axis.

Temozolomide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Glioma [ICD-11: 2A00.1] [6]

• Resistant Disease: Glioma [ICD-11: 2A00.1]
• Resistant Drug: Temozolomide
• Molecule Alteration: Expression; .
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: NEAT1/miR-454-3p/Connexin 43 signaling pathway; Regulation; N.A.
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: The results showed that recurring gliomas displayed elevated levels of NEAT1 compared to primary gliomas. The suppression of NEAT1 led to a restoration of sensitivity in GBM cells to TMZ. NEAT1 functioned as a competitive endogenous RNA against miR-454-3p. Connexin 43 was identified as a miR-454-3p target. NEAT1 was found to regulate gap junctional intercellular communication by modulating Connexin 43, thereby impacting the response of GBM cells to TMZ chemotherapy. Downregulation of NEAT1 resulted in enhanced chemosensitivity to TMZ and extended the survival of mice.

Investigative Drug(s) 3 drug(s) in total

Cisplatinum

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [7]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Resistant Drug: Cisplatinum
• Molecule Alteration: Down-regulation; Interaction
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SPC-A1 cells; Lung; Homo sapiens (Human); CVCL_6955
• In Vitro Model: NCI-H520 cells; Lung; Homo sapiens (Human); CVCL_1566
• In Vitro Model: NCI-H1299 cells; Lymph node; Homo sapiens (Human); CVCL_0060
• In Vivo Model: BALB/c nude mice model; Mus musculus
• Experiment for Molecule Alteration: Overexpression assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: TUG1 overexpression was shown to inhibit cell proliferation, migration, invasion, but facilitate apoptosis and autophagy in NSCLC cells resistant to cisplatin (DDP).

Lipopolysaccharide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Hepatic cirrhosis [ICD-11: DB93.1] [7]

• Resistant Disease: Hepatic cirrhosis [ICD-11: DB93.1]
• Resistant Drug: Lipopolysaccharide
• Molecule Alteration: Up-regulation; Interaction
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: LSECs; Liver; Homo sapiens (Human); CVCL_QY34
• Experiment for Molecule Alteration: Knockdown assay; Overexpression assay; qRT-PCR; Western bloting analysis; Co-immunofluorescence staining; Immunohistochemical assay; RNA-seq; Luciferase assay; FISH assay; RIP experiments assay; ELISA assay
• Experiment for Drug Resistance: WST assay; Flow cytometry assay; Transwell assay
• Mechanism Description: TUG1 promotes LPS-induced autophagy and EndMT of LSECs by functioning as an endogenous sponge for miR-142-3p and promoting the expression of A TG5. LPS and miR-142-3p are potential diagnostic and therapeutic targets in cirrhosis.

Picric acid

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Irritable bowel syndrome [ICD-11: DD91.0] [7]

• Resistant Disease: Irritable bowel syndrome [ICD-11: DD91.0]
• Resistant Drug: Picric acid
• Molecule Alteration: Down-regulation; Interaction
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ICCs; Breast; Homo sapiens (Human); CVCL_B5N7
• Experiment for Molecule Alteration: qRT-PCR; Western bloting analysis; Overexpression assay
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: TUG1 attenuated TNF-alpha-caused apoptosis and inflammatory response in ICC by down-regulating miR-127 and then inactivating NF-kappa-B and Notch pathways.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Esophageal cancer [ICD-11: 2B70]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Esophagus
• The Specified Disease: Esophageal carcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.36E-29; Fold-change: -3.06E-02

Colorectal cancer [ICD-11: 2B91]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Rectum
• The Specified Disease: Rectum adenocarcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.40E-02; Fold-change: -3.43E-02

Pancreatic cancer [ICD-11: 2C10]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Pancreas
• The Specified Disease: Pancreatic adenocarcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.62E-22; Fold-change: -4.73E-02

Lung cancer [ICD-11: 2C25]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Lung
• The Specified Disease: Lung adenocarcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 9.33E-16; Fold-change: 2.56E-02
• The Studied Tissue: Lung
• The Specified Disease: Lung squamous cell carcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.06E-01; Fold-change: -2.19E-03

References

• Ref 1: LncRNA TUG1 promoted viability and associated with gemcitabine resistant in pancreatic ductal adenocarcinoma. J Pharmacol Sci. 2018 Jun;137(2):116-121. doi: 10.1016/j.jphs.2018.06.002. Epub 2018 Jun 7.
• Ref 2: LncRNA TUG1 promotes cisplatin resistance in esophageal squamous cell carcinoma cells by regulating Nrf2. Acta Biochim Biophys Sin (Shanghai). 2019 Aug 5;51(8):826-833. doi: 10.1093/abbs/gmz069.
• Ref 3: Long non-coding RNA TUG1 sponges miR-197 to enhance cisplatin sensitivity in triple negative breast cancer. Biomed Pharmacother. 2018 Nov;107:338-346. doi: 10.1016/j.biopha.2018.07.076. Epub 2018 Aug 8.
• Ref 4: TUG1 confers Adriamycin resistance in acute myeloid leukemia by epigenetically suppressing miR-34a expression via EZH2. Biomed Pharmacother. 2019 Jan;109:1793-1801. doi: 10.1016/j.biopha.2018.11.003. Epub 2018 Nov 26.
• Ref 5: TUG1 mediates methotrexate resistance in colorectal cancer via miR-186/CPEB2 axis. Biochem Biophys Res Commun. 2017 Sep 16;491(2):552-557. doi: 10.1016/j.bbrc.2017.03.042. Epub 2017 Mar 14.
• Ref 6: Inhibiting lncRNA NEAT1 Increases Glioblastoma Response to TMZ by Reducing Connexin 43 Expression. Cancer Rep (Hoboken). 2024 Oct;7(10):e70031.
• Ref 7: Long non-coding RNA TUG1 enhances chemosensitivity in non-small cell lung cancer by impairing microRNA-221-dependent PTEN inhibitionAging (Albany NY). 2019 Sep 18;11(18):7553-7569. doi: 10.18632/aging.102271. Epub 2019 Sep 18.