Results

RDF/XMLNTriplesTurtleShow queryShare
SubjectPredicateObject
http://purl.uniprot.org/citations/29136760http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/29136760http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Numerous studies suggested autophagy was involved in temozolomide (TMZ) resistance in glioma. Long non-coding RNA (lncRNA) CASC2 was shown to be downregulated in glioma tissues and cell lines, and was related to the TMZ resistance. However, whether CASC2 affects TMZ resistance through regulating autophagy is unknown. The aim of this study was to assess the role and mechanism of CASC2 in TMZ-induced drug resistance in glioma cells.

Methods

Glioma and the adjacent non-cancerous tissues from 32 patients were collected. The expressions of CASC2 and miR-193a-5p were determined by PCR, and their correlation was analyzed. The correlation between CASC2 expression and the clinical characteristics of patients was also studied. Glioma cells were treated with TMZ to acquire the TMZ-resistant cell lines in which the expressions of CASC2, miR-193a-5p, and mTOR were measured. The regulatory roles of CASC2, miR-193a-5p, and mTOR were defined through the loss of function and luciferase reporter assays. Autophagy was inhibited by autophagy inhibitor 3-MA, CASC2 and mTOR overexpression, or miR-193a-5p inhibitor, and the effect of which on cell viability, apoptosis, and migration of TMZ-resistant glioma cells was evaluated.

Results

CASC2 downregulation and miR-193a-5p upregulation was found to be associated with advanced clinical stage and TMZ response in patients with glioma. CASC2 negatively regulates miR-193a-5p expression by direct interaction in glioma cells. Overexpression of CASC2 or inhibition of miR-193a-5p reduced TMZ-induced autophagy via mTOR upregulation, which makes the glioma cells become sensitive to TMZ cytotoxicity.

Conclusion

CASC2 is downregulated in gliomas, resulting in increased miR-193a-5p level and a decrease in mTOR expression, which further induces protective autophagy, leading to TMZ resistance. Inhibition of autophagy helps to increase the efficacy of TMZ."xsd:string
http://purl.uniprot.org/citations/29136760http://purl.org/dc/terms/identifier"doi:10.1016/j.biopha.2017.10.146"xsd:string
http://purl.uniprot.org/citations/29136760http://purl.uniprot.org/core/author"Du J."xsd:string
http://purl.uniprot.org/citations/29136760http://purl.uniprot.org/core/author"Huang X."xsd:string
http://purl.uniprot.org/citations/29136760http://purl.uniprot.org/core/author"Liu Z."xsd:string
http://purl.uniprot.org/citations/29136760http://purl.uniprot.org/core/author"Li X."xsd:string
http://purl.uniprot.org/citations/29136760http://purl.uniprot.org/core/author"Jiang C."xsd:string
http://purl.uniprot.org/citations/29136760http://purl.uniprot.org/core/author"Su J."xsd:string
http://purl.uniprot.org/citations/29136760http://purl.uniprot.org/core/author"Wang X."xsd:string
http://purl.uniprot.org/citations/29136760http://purl.uniprot.org/core/author"Fang X."xsd:string
http://purl.uniprot.org/citations/29136760http://purl.uniprot.org/core/author"Shen F."xsd:string
http://purl.uniprot.org/citations/29136760http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/29136760http://purl.uniprot.org/core/name"Biomed Pharmacother"xsd:string
http://purl.uniprot.org/citations/29136760http://purl.uniprot.org/core/pages"844-850"xsd:string
http://purl.uniprot.org/citations/29136760http://purl.uniprot.org/core/title"Upregulation of CASC2 sensitized glioma to temozolomide cytotoxicity through autophagy inhibition by sponging miR-193a-5p and regulating mTOR expression."xsd:string
http://purl.uniprot.org/citations/29136760http://purl.uniprot.org/core/volume"97"xsd:string
http://purl.uniprot.org/citations/29136760http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/29136760
http://purl.uniprot.org/citations/29136760http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/29136760
http://purl.uniprot.org/uniprot/#_Q6XLA1-mappedCitation-29136760http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29136760
http://purl.uniprot.org/uniprot/#_Q8IU53-mappedCitation-29136760http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29136760
http://purl.uniprot.org/uniprot/Q6XLA1http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/29136760
http://purl.uniprot.org/uniprot/Q8IU53http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/29136760