Cargando…
LncRNA DLGAP1-AS2 promotes the radioresistance of rectal cancer stem cells by upregulating CD151 expression via E2F1
BACKGROUND: Radiotherapy resistance is one of the major causes of rectal cancer treatment failure. LncRNA DLGAP1-AS2 participates in the progression of several cancers. We explored the role and potential mechanism of DLGAP1-AS2 in the radioresistance of rectal cancer stem cells. METHODS: HR8348-R ce...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8844799/ https://www.ncbi.nlm.nih.gov/pubmed/35144091 http://dx.doi.org/10.1016/j.tranon.2021.101304 |
Sumario: | BACKGROUND: Radiotherapy resistance is one of the major causes of rectal cancer treatment failure. LncRNA DLGAP1-AS2 participates in the progression of several cancers. We explored the role and potential mechanism of DLGAP1-AS2 in the radioresistance of rectal cancer stem cells. METHODS: HR8348-R cells, radioresistant cells from HR8348 after irradiation, were isolated into CD133 negative (CD133(−)) and positive (CD133(+)) cells. Cell proliferation, apoptosis, migration and tumorsphere formation were determined by CCK-8, flow cytometry, wound healing assay and tumorsphere formation assay, respectively. CD133, tumor stem cell drug resistance gene (MDR1 and BCRP1), DNA repair marker (γ-H2AX) and AKT/mTOR/cyclinD1 signaling were measured by Western blot. The relationship between DLGAP1-AS2 and E2F1 was verified using RIP. The interaction between E2F1 and CD151 promoter was confirmed using dual-luciferase reporter gene assay and ChIP. AKT inhibitor API-2 was employed for validating the effect of AKT/mTOR/cyclinD1 signaling in the radioresistance of rectal cancer cells. RESULTS: The DLGAP1-AS2 level was increased in CD133(+) cells after irradiation. DLGAP1-AS2 knockdown inhibited the proliferation, migration and tumorsphere formation while stimulating apoptosis in CD133(+) cells. DLGAP1-AS2 inhibition downregulated the expression of CD133, MDR1, BCRP1 and γ-H2AX and suppressed AKT/mTOR/cyclinD1 activation. DLGAP1-AS2 upregulated the expression of CD151 by interacting with E2F1. API-2 neutralized the promotive effects of overexpressed CD151 on radioresistance. CONCLUSION: DLGAP1-AS2 accelerates the radioresistance of rectal cancer cells through interactions with E2F1 to upregulate CD151 expression via the activation of the AKT/mTOR/cyclinD1 pathway. |
---|