Downregulation of lncRNA CCDC26 contributes to imatinib resistance in human gastrointestinal stromal tumors through IGF-1R upregulation
Braz. j. med. biol. res
;
52(6): e8399, 2019. graf
Artigo
em Inglês
| LILACS
| ID: biblio-1011582
ABSTRACT
Imatinib is the first line of therapy for patients with metastatic or gastrointestinal stromal tumors (GIST). However, drug resistance limits the long-term effect of imatinib. Long non-coding RNAs (lncRNAs) are emerging as key players in regulating drug resistance in cancer. In this study, we investigated the association between lncRNA CCDC26 and IGF-1R in GIST and their involvement in drug resistance. Considering the key role of lncRNAs in drug resistance in cancer, we hypothesized that IGF-1R is regulated by lncRNAs. The expression of a series of reported drug resistance-related lncRNAs, including CCDC26, ARF, H19, NBR2, NEAT1, and HOTAIR, in GIST cells treated with imatinib H19 was examined at various time-points by qRT-PCR. Based on our results and published literature, CCDC26, a strongly down-regulated lncRNA following imatinib treatment, was chosen as our research target. GIST cells with high expression of CCDC26 were sensitive to imatinib treatment while knockdown of CCDC26 significantly increased the resistance to imatinib. Furthermore, we found that CCDC26 interacted with c-KIT by RNA pull down, and that CCDC26 knockdown up-regulated the expression of IGF-1R. Moreover, IGF-1R inhibition reversed CCDC26 knockdown-mediated imatinib resistance in GIST. These results indicated that treatments targeting CCDC26-IGF-1R axis would be useful in increasing sensitivity to imatinib in GIST.
Texto completo:
DisponíveL
Índice:
LILACS (Américas)
Assunto principal:
Receptores de Somatomedina
/
Resistencia a Medicamentos Antineoplásicos
/
Peptídeos e Proteínas de Sinalização Intracelular
/
RNA Longo não Codificante
/
Mesilato de Imatinib
/
Antineoplásicos
Limite:
Humanos
Idioma:
Inglês
Revista:
Braz. j. med. biol. res
Assunto da revista:
Biologia
/
Medicina
Ano de publicação:
2019
Tipo de documento:
Artigo
País de afiliação:
China
Instituição/País de afiliação:
First Affiliated Hospital of Wenzhou Medical University/CN
/
Tongde Hospital of Zhejiang Province/CN
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