JMJD1C knockdown affects myeloid cell lines proliferation, viability, and gemcitabine/carboplatin-sensitivity.
Pharmacogenet Genomics
; 31(3): 60-67, 2021 04 01.
Article
in En
| MEDLINE
| ID: mdl-33075016
ABSTRACT
OBJECTIVES:
Chemotherapy-induced hematological toxicities are potentially life-threatening adverse drug reactions that vary between individuals. Recently, JMJD1C has been associated with gemcitabine/carboplatin-induced thrombocytopenia in non-small-cell lung cancer patients, making it a candidate marker for predicting the risk of toxicity. This study investigates if JMJD1C knockdown affects gemcitabine/carboplatin-sensitivity in cell lines.METHODS:
Lentiviral transduction-mediated shRNA knockdown of JMJD1C in the cell lines K562 and MEG-01 were performed using shRNA#32 and shRNA#33. The knockdown was evaluated using qPCR. Cell proliferation, viability, and gemcitabine/carboplatin-sensitivity were subsequently determined using cell counts, trypan blue, and the MTT assay.RESULTS:
ShRNA#33 resulted in JMJD1C downregulation by 56.24% in K562 and 68.10% in MEG-01. Despite incomplete knockdown, proliferation (reduction of cell numbers by 61-68%, day 7 post-transduction) and viability (reduction by 21-53%, day 7 post-transduction) were impaired in K562 and MEG-01 cells. Moreover, JMJD1C knockdown reduced the gemcitabine IC50-value for K562 cells (P < 0.01) and MEG-01 cells (P < 0.05) compared to scrambled shRNA control transduced cells.CONCLUSIONS:
Our results suggest that JMJD1C is essential for proliferation, survival, and viability of K562 and MEG-01 cells. Further, JMJD1C also potentially affects the cells gemcitabine/carboplatin-sensitivity. Although further research is required, the findings show that JMJD1C could have an influential role for gemcitabine/carboplatin-sensitivity.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oxidoreductases, N-Demethylating
/
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
/
Cell Proliferation
/
Jumonji Domain-Containing Histone Demethylases
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Pharmacogenet Genomics
Journal subject:
FARMACOLOGIA
/
GENETICA MEDICA
Year:
2021
Document type:
Article
Affiliation country:
Sweden