Molecule Information

General Information of the Molecule (ID: Mol01291)

• Name: Lung cancer associated transcript 1 (LUCAT1) ,Homo sapiens
• Synonyms: LUCAT1
• Molecule Type: LncRNA
• Gene Name: RP11-159F24.1
• Gene ID: 100505994
• Location: chr5:91054834-91314547[-]
• Ensembl ID: ENSG00000248323
• HGNC ID: HGNC:48498

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

Drug Resistance Data Categorized by Drug

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

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Non-small cell lung cancer [ICD-11: 2C25.0] [1]

• Resistant Disease: Non-small cell lung cancer [ICD-11: 2C25.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: miR-514a-3p/ULK1 axis; Regulation; N.A.
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: By using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), it was found that the expression of LUCAT1 was elevated and that of microRNA-514a-3p (miR-514a-3p) was decreased in DDP-resistant NSCLC tissues and cells. Functionally, LUCAT1 upregulation enhanced cisplatin resistance by promoting the viability, autophagy and metastasis, and inhibiting the apoptosis of NSCLC cells, as demonstrated by Cell Counting kit-8 (CCK-8) assay, western blot analysis, Transwell assay and flow cytometric analysis. LUCAT1 was identified as a sponge of miR-514a-3p and uncoordinated-51-like kinase 1 (ULK1) was proven to be a target gene of miR-514a-3p by bioinformatics analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The enhancing effect of miR-514a-3p on cisplatin sensitivity was reversed by the elevation of LUCAT1. ULK1 knockdown suppressed cisplatin resistance, while this effect was attenuated by miR-514a-3p inhibition. Moreover, LUCAT1 positively regulated ULK1 expression by targeting miR-514a-3p. In addition, LUCAT1 knockdown suppressed tumor growth in vivo. On the whole, the findings of the present study demonstrate that LUCAT1 contributes to the resistance of NSCLC cells to cisplatin by regulating the miR-514a-3p/ULK1 axis, elucidating a novel regulatory network in cisplatin resistance in NSCLC.

Methotrexate

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Osteosarcoma [ICD-11: 2B51.0] [2]

• Resistant Disease: Osteosarcoma [ICD-11: 2B51.0]
• Resistant Drug: Methotrexate
• 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 proliferation; Activation; hsa05200
• Cell Pathway Regulation: LUCAT1/miR200c/ABCB1 pathway; Regulation; N.A.
• 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
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• In Vitro Model: HOS cells; Bone; Homo sapiens (Human); CVCL_0312
• In Vitro Model: HFOB cells; Bone; Homo sapiens (Human); CVCL_3708
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: CCK8 assay; Transwell invasion assay
• Mechanism Description: The modulation of LUCAT1 on ABCB1 through sponging miR200c. LncRNA LUCAT1 knockdown suppress the expression levels drug resistance related genes, proliferation, invasion and tumor growth of osteosarcoma cells in vitro and vivo, hence, LUCAT1 upregulation leads to improved chemoresistance.

Temozolomide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Glioblastoma [ICD-11: 2A00.02] [3]

• Resistant Disease: Glioblastoma [ICD-11: 2A00.02]
• Resistant Drug: Temozolomide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Interaction network and functional enrichment analysis; Differential expression analysis
• Experiment for Drug Resistance: Data analysis
• Mechanism Description: Of the 34 lncRNAs, LUCAT1, TCL6, MIR4458HG and LINC00114 may play a vital role in TMZ chemotherapy resistance of GBM cells. Yansheng gao et al. revealed that LUCAT1 could act as a oncogenic lncRNA and promote glioma tumorigenesis via regulating miR-375.

References

• Ref 1: Indian J Med Paediatr Oncol. 2015 Apr-Jun;36(2):133-6. doi: 10.4103/0971-5851.158852.
• Ref 2: Long non-coding RNA LUCAT1 modulates methotrexate resistance in osteosarcoma via miR-200c/ABCB1 axis. Biochem Biophys Res Commun. 2018 Jan 1;495(1):947-953. doi: 10.1016/j.bbrc.2017.11.121. Epub 2017 Nov 21.
• Ref 3: MicroRNA-212-3p inhibits paclitaxel resistance through regulating epithelial-mesenchymal transition, migration and invasion by targeting ZEB2 in human hepatocellular carcinoma. Oncol Lett. 2020 Oct 20(4):23