Molecule Information

General Information of the Molecule (ID: Mol02203)

• Name: Nuclear paraspeckle assembly transcript 1 (NEAT1) ,Danio rerio
• Synonyms: NEAT1
• Molecule Type: LncRNA
• Gene Name: NEAT1

Kingdom: Metazoa
Phylum: Chordata
Class: Actinopteri
Order: Cypriniformes
Family: Danionidae
Genus: Danio
Species: Danio rerio

Type(s) of Resistant Mechanism of This Molecule

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  MRAP: Metabolic Reprogramming via Altered Pathways

  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

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Medulloblastoma [ICD-11: 2A00.10] [1]

• Metabolic Type: Glutamine metabolism
• Resistant Disease: Medulloblastoma [ICD-11: 2A00.10]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: D341 cells; Brain; Homo sapiens (Human); CVCL_0018
• In Vitro Model: DAOY cells; Brain; Homo sapiens (Human); CVCL_1167
• In Vitro Model: UW228 cells; Brain; Homo sapiens (Human); CVCL_8585
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: In cisplatin-resistant MB cell line, DAOY Cis R, NEAT1 expression, and glutamine metabolism were remarkably upregulated in cisplatin-resistant cells. Under low glutamine supply, cisplatin-resistant cells displayed increased cisplatin sensitivity. Bioinformatical analysis and luciferase assay uncovered that NEAT1 functions as a ceRNA of miR-23a-3p to downregulate its expressions in MB cells. Moreover, miR-23a-3p was apparently downregulated in MB patient tissues and cisplatin resistant MB cells. We identified GLS (glutaminase), a glutamine metabolism enzyme, was directly targeted by miR-23a-3p in MB cells.

Temozolomide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

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

• Resistant Disease: Glioma [ICD-11: 2A00.1]
• Resistant Drug: Temozolomide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: NEAT1/miR-454-3p/Connexin 43 signaling pathway; Regulation; N.A.
• In Vivo Model: Normal brain tissues; Patient-derived primary GBM model; Patient-derived recurrent GBM model; Homo sapiens
• Experiment for Molecule Alteration: qRT-PCR
• 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.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

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

• Sensitive Disease: Glioma [ICD-11: 2A00.1]
• Sensitive Drug: Temozolomide
• Molecule Alteration: Expression; .
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: NEAT1/miR-454-3p/Connexin 43 signaling pathway; Regulation; N.A.
• In Vivo Model: shNEAT1 mouse model; Mus musculus
• 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) 1 drug(s) in total

Isoliquiritigenin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Brain glioma [ICD-11: 2A00.0] [3]

• Resistant Disease: Brain glioma [ICD-11: 2A00.0]
• Resistant Drug: Isoliquiritigenin
• Molecule Alteration: Down-regulation; Interaction
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: C6 cells; Brain; Rattus norvegicus (Rat); CVCL_0194
• Experiment for Molecule Alteration: qRT-PCR; Western bloting analysis; Immunofluorescence assay; ELISA assay; Luciferase assay; Overexpression assay
• Mechanism Description: LncRNA NEAT1 overexpression reversed ISL-mediated increase in miR-194-5p expression, and thereby attenuated FGF-2, TGF-beta and VEGF production.

References

• Ref 1: Inhibition of lncRNA NEAT1 sensitizes medulloblastoma cells to cisplatin through modulating the miR-23a-3p-glutaminase (GLS) axis. Bioengineered. 2022 Mar;13(3):7670-7682.
• Ref 2: Inhibiting lncRNA NEAT1 Increases Glioblastoma Response to TMZ by Reducing Connexin 43 Expression. Cancer Rep (Hoboken). 2024 Oct;7(10):e70031.
• Ref 3: Inhibition of COX-2, mPGES-1 and CYP4A by isoliquiritigenin blocks the angiogenic Akt signaling in glioma through ceRNA effect of miR-194-5p and lncRNA NEAT1J Exp Clin Cancer Res. 2019 Aug 22;38(1):371. doi: 10.1186/s13046-019-1361-2.