English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Background  Noncoding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are becoming key parts in the development of multidrug resistance (MDR) in T-cell acute lymphoblastic leukemia (T-ALL). Abnormal expression in sialyated  N -glycans have been observed in MDR leukemia. However, the role of sialylation regulated MDR remains poorly understood. The aim of this work is to analyze the alternation of  N -glycans in T-ALL MDR.    Methods  Here, mass spectrometry (MS) is analyzed to screen the  N -glycan profiles from ALL cell line CR and adriamycin (ADR)-resistant CR (CR/A) cells. The expression of sialyltransferase (ST) genes in T-ALL cell lines and bone marrow mononuclear cells (BMMCs) of T-ALL patients were analyzed using qRT-PCR. Functionally, T-ALL cell proliferation and MDR are detected through CCK8 assay, colony formation assay, western blot and flow cytometry. RIP assay and Dual-luciferase reporter gene assay confirm the binding association between ZFAS1 and miR-150. Xenograft nude mice models are used to determine the role of ST6GAL1 in vivo.    Results  Elevated expression of α2, 6-sialyltransferase 1 (ST6GAL1) has been detected. The altered level of ST6GAL1 was corresponding to the drug-resistant phenotype of T-ALL cell lines both in vitro and in vivo. ZFAS1/miR-150/ST6GAL1 axis was existed in T-ALL cell lines. MiR-150 was downregulated and inversely correlated to ST6GAL1 expression. ZFAS1 was a direct target of miR-150 and positively modulated ST6GAL1 level by binding miR-150. ZFAS1/miR-150/ST6GAL1 axis functioned to regulate ADR-resistant cell growth and apoptosis. Besides, EGFR was demonstrated to be a substrate of ST6GAL1, and the sialylated EGFR had an impact on the PI3K/Akt pathway.    Conclusion  Results suggested that ZFAS1/miR-150/ST6GAL1 axis involves in the progression of T-ALL/MDR further mediates sialylated EGFR via PI3K/Akt pathway. This work might have an application against T-ALL MDR.    Electronic supplementary material  The online version of this article (10.1186/s13046-019-1208-x) contains supplementary material, which is available to authorized users.

The regulatory ZFAS1/miR-150/ST6GAL1 crosstalk modulates sialylation of EGFR via PI3K/Akt pathway in T-cell acute lymphoblastic leukemia