MiR-503 Contributes to Glucocorticoid Sensitivity in Acute Lymphoblastic Leukaemia via Targeting WNT3A
Jazyk angličtina Země Česko Médium print
Typ dokumentu časopisecké články
PubMed
35439853
DOI
10.14712/fb2021067050199
PII: file/5965/fb2021a0025.pdf
Knihovny.cz E-zdroje
- MeSH
- akutní lymfatická leukemie * farmakoterapie genetika metabolismus MeSH
- beta-katenin MeSH
- dexamethason farmakologie terapeutické užití MeSH
- glukokortikoidy farmakologie terapeutické užití MeSH
- lidé MeSH
- messenger RNA MeSH
- mikro RNA * genetika metabolismus MeSH
- protein Wnt3A terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- beta-katenin MeSH
- dexamethason MeSH
- glukokortikoidy MeSH
- messenger RNA MeSH
- mikro RNA * MeSH
- MIRN503 microRNA, human MeSH Prohlížeč
- protein Wnt3A MeSH
- WNT3A protein, human MeSH Prohlížeč
Abnormal accumulation of lymphoblasts in the blood and bone marrow is the main characteristic of acute lymphoblastic leukaemia (ALL). Glucocorticoids are effective drugs for ALL, while glucocorticoid resistance is an obstacle to ALL therapy. MicroRNAs (miRNAs) are implicated in the drug resistance and modulate the response of ALL to glucocorticoids. The role of miR-503 in glucocorticoid sensitivity of ALL was investigated in this study. Firstly, T-leukaemic cells were isolated from patients with ALL. The human ALL cell line (CCRF/CEM) was incubated with dexamethasone to establish a glucocorticoid- resistant ALL cell line (CCRF/CEM-R). Data from MTT showed that IC50 (50% inhibitory concentration) of dexamethasone in T-leukaemic cells isolated from glucocorticoid-resistant ALL patients or CCRF/CEM-R was increased compared with IC50 in T-leukaemic cells isolated from glucocorticoid- sensitive ALL patients or CCRF/CEM. MiR- 503 was down-regulated in glucocorticoid-resistant leukaemic cells and CCRF/CEM-R. Secondly, overexpression of miR-503 sensitized CCRF/CEM-R to dexamethasone. Moreover, over-expression of miR- 503 also promoted the sensitivity of ALL cells to dexamethasone. Thirdly, miR-503 bound to WNT3A mRNA and negatively regulated the expression of WNT3A. Over-expression of miR-503 reduced protein expression of nuclear β-catenin, and over-expression of WNT3A attenuated the miR-503 overexpression- induced decrease in nuclear β-catenin. Lastly, the over-expression of miR-503-induced increased sensitivity of ALL-resistant cells and CCRF/ CEM-R to dexamethasone was attenuated by overexpression of WNT3A. In conclusion, miR-503 targeted WNT3A mRNA to sensitize ALL cells to glucocorticoids through inactivation of the Wnt/β-catenin pathway.
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