FOXO3-induced oncogenic lncRNA CASC9 enhances gefitinib resistance of non-small-cell lung cancer through feedback loop.
Life Sci
; 287: 120012, 2021 Dec 15.
Article
in En
| MEDLINE
| ID: mdl-34619168
ABSTRACT
Gefitinib is tyrosine kinase inhibitor of epidermal growth factor receptor, which exhibits notable clinical efficacy in non-small-cell lung cancer (NSCLC) treatment. However, gefitinib resistance is a critical obstacle for NSCLC targeted therapy. Here, we investigated the biological functions and mechanisms of lncRNA CASC9 in NSCLC gefitinib resistance. Screening analysis and RT-qPCR demonstrated that CASC9 was up-regulated in the gefitinib-resistant NSCLC cells (PC9/GR). Moreover, high-expression of CASC9 acted as an unfavorable factor for NSCLC patients. Functionally, CASC9 promoted the proliferation and gefitinib resistance of PC9/GR cells in vitro, and knockdown of CASC9 repressed the tumor growth in vivo. Mechanistically, CASC9 epigenetically promoted the FOXO3 expression via inhibiting miR-195-5p. In turn, transcription factor FOXO3 bound with the promoter region of CASC9 to enhance CASC9 transcriptional level, thereby forming CASC9/miR-195-5p/FOXO3 positive feedback loop. In conclusion, our research identified the regulation of CASC9/miR-195-5p/FOXO3 feedback loop on NSCLC gefitinib resistance, which might help researchers develop potential therapeutic targets for NSCLC.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Non-Small-Cell Lung
/
RNA, Long Noncoding
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Carcinogenesis
/
Forkhead Box Protein O3
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Gefitinib
/
Lung Neoplasms
Type of study:
Prognostic_studies
Limits:
Aged
/
Animals
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Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Life Sci
Year:
2021
Type:
Article
Affiliation country:
China