Proteasome Inhibitors Interrupt the Activation of Non-Canonical NF-κB Signaling Pathway and Induce Cell Apoptosis in Cytarabine-Resistant HL60 Cells

Wang, Shuo-Yu; Shih, Yin-Hwa; Shieh, Tzong‐Ming; Tseng, Yu‐Hsin

doi:10.3390/ijms23010361

Cited by 8 publications

(5 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Acquired resistance to venetoclax in AML cell lines is dependent on NF-κB activation 38 , and the expression of numerous genes associated with the NF-κB signaling pathway is also altered during the development of cytarabine resistance. Proteasome inhibitors that reduce the activity of NF-κB signaling pathway could induce apoptosis in cytarabine-resistant AML cells 39 . Additionally, NF-κB facilitates establishing AML drug resistance by controlling P-gp-mediated expression of the MDR1 gene 40 .…”

Section: Discussionmentioning

confidence: 99%

GNL3L exhibits pro-tumor activities via NF-κB pathway as a poor prognostic factor in acute myeloid leukemia

Li,

Wu,

Pan

et al. 2024

J. Cancer

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

GNL3L exhibits pro-tumor activities via NF-κB pathway as a poor prognostic factor in acute myeloid leukemia

Li,

Wu,

Pan

et al. 2024

J. Cancer

View full text Add to dashboard Cite

“…Following the methods in study [ 21 ], MOLM13 and MV4-11 cells are cultivated in IMDM medium supplemented with 10% fetal bovine serum, maintained at 37 °C in a 5% CO 2 environment, and sub-cultured every 2–3 days. For drug-resistance establishment, the induction begins at IC50 of cytarabine.…”

Section: Methodsmentioning

confidence: 99%

Spatiotemporal evolution of AML immune microenvironment remodeling and RNF149-driven drug resistance through single-cell multidimensional analysis

Wu,

Deng

et al. 2023

J Transl Med

View full text Add to dashboard Cite

Background The composition of the bone marrow immune microenvironment in patients with acute myeloid leukaemia (AML) was analysed by single-cell sequencing and the evolutionary role of different subpopulations of T cells in the development of AML and in driving drug resistance was explored in conjunction with E3 ubiquitin ligase-related genes. Methods To elucidate the mechanisms underlying AML-NR and Ara-C resistance, we analyzed the bone marrow immune microenvironment of AML patients by integrating multiple single-cell RNA sequencing datasets. When compared to the AML disease remission (AML-CR) cohort, AML-NR displayed distinct cellular interactions and alterations in the ratios of CD4+T, Treg, and CD8+T cell populations. Results Our findings indicate that the E3 ubiquitin ligase RNF149 accelerates AML progression, modifies the AML immune milieu, triggers CD8+T cell dysfunction, and influences the transformation of CD8+ Navie.T cells to CD8+TExh, culminating in diminished AML responsiveness to chemotherapeutic agents. Experiments both in vivo and in vitro revealed RNF149’s role in enhancing AML drug-resistant cell line proliferation and in apoptotic inhibition, fostering resistance to Ara-C. Conclusion In essence, the immune microenvironments of AML-CR and AML-NR diverge considerably, spotlighting RNF149’s tumorigenic function in AML and cementing its status as a potential prognostic indicator and innovative therapeutic avenue for countering AML resistance. Graphical Abstract

show abstract

“…Intensive therapy with high-dose cytarabine improves the overall survival rate and reduces AML recurrence; however, the risk of drug-related side effects is also increased. AML treatment in older patients has not improved significantly in recent decades compared with that in younger patients ( 7 ). A more thorough understanding of the drug resistance mechanisms is required to provide effective cancer treatments and improve outcomes.…”

Section: Introductionmentioning

confidence: 99%

“…Cytarabine then incorporates into DNA strands during the S phase of the cell cycle to inhibit DNA synthesis ( 8 ). Insufficient cellular uptake and retention of cytarabine, overexpression of enzymes that inactivate cytarabine, increased cellular deoxycytidine triphosphate (dCTP) pool, and increased DNA repair are the main mechanisms of cytarabine resistance ( 7 ). Overall, the reduced expression of human equilibrating nucleoside transporter 1 (hENT1) and deoxycytidine kinase (dCK) play pivotal roles during the development of cytarabine resistance in leukemia cells ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

“…Insufficient cellular uptake and retention of cytarabine, overexpression of enzymes that inactivate cytarabine, increased cellular deoxycytidine triphosphate (dCTP) pool, and increased DNA repair are the main mechanisms of cytarabine resistance (7). Overall, the reduced expression of human equilibrating nucleoside transporter 1 (hENT1) and deoxycytidine kinase (dCK) play pivotal roles during the development of cytarabine resistance in leukemia cells (7). However, other new mechanisms associated with cytarabine resistance have been discovered consecutively.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prediction of miRNA‑mRNA network regulating the migration ability of cytarabine‑resistant HL60 cells

Hsu,

Chiou,

Lin

et al. 2023

Biomed Rep

Self Cite

View full text Add to dashboard Cite

Cytarabine is an important medicine for acute myeloid leukemia (AML) treatment, however, drug resistance hinders the treatment of AML. Although microRNA (miRNA or miR) alteration is one of the well-recognized mechanisms underlying drug resistance in AML, few studies have investigated the role and function of miRNAs in the development of cytarabine resistance. In the present study, total RNA was isolated from parental HL60 and cytarabine-resistant HL60 (R-HL60) cells. Subsequently, miRNAs and mRNAs were detected using small RNA sequencing and gene expression array, respectively. Differentially expressed mRNAs (DEMs) and differentially expressed genes (DEGs) with more than two-fold changes between HL60 and R-HL60 cells were screened out. Negatively associated miRNA-mRNA pairs were selected as candidate miRNA-mRNA target pairs according to the miRDB, Targetscan or miRTar databases. Functional enrichment analysis of DEGs included in the candidate miRNA-mRNA pairs was performed. The results indicated that 10 DEGs ( CCL2 , SOX9 , SLC8A1 , ICAM1 , CXCL10 , SIPR2 , FGFR1 , OVOL2 , MITF and CARD10) were simultaneously involved in seven Gene Ontology pathways related to the regulation of migration ability, namely the ‘regulation of cell migration’, ‘regulation of locomotion’, ‘regulation of cellular component movement’, ‘cell migration’, ‘locomotion’, ‘cell motility’, and ‘localization of cell’. DEMs predicted to negatively regulate the aforementioned 10 DEGs were paired with DEGs into 16 candidate miRNA-mRNA pairs related to the regulation of migration ability. In addition, migration assays revealed that the migration ability of R-HL60 cells was greater than that of HL60 cells. These findings provide a new perspective for the treatment of cytarabine-resistant AML and advance our understanding of altered migration ability underlying cytarabine resistance development, specifically related to miRNAs.

show abstract

Proteasome Inhibitors Interrupt the Activation of Non-Canonical NF-κB Signaling Pathway and Induce Cell Apoptosis in Cytarabine-Resistant HL60 Cells

Cited by 8 publications

References 63 publications

GNL3L exhibits pro-tumor activities via NF-κB pathway as a poor prognostic factor in acute myeloid leukemia

GNL3L exhibits pro-tumor activities via NF-κB pathway as a poor prognostic factor in acute myeloid leukemia

Spatiotemporal evolution of AML immune microenvironment remodeling and RNF149-driven drug resistance through single-cell multidimensional analysis

Prediction of miRNA‑mRNA network regulating the migration ability of cytarabine‑resistant HL60 cells

Contact Info

Product

Resources

About