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Knockdown of homeobox A5 by small hairpin RNA inhibits proliferation and enhances cytarabine chemosensitivity of acute myeloid leukemia cells
- Source :
- Molecular medicine reports. 12(5)
- Publication Year :
- 2014
-
Abstract
- Homeobox genes encode transcription factors that are essential for embryonic morphogenesis and differentiation. Transcription factors containing the highly conserved homeobox motif show considerable promise as potential regulators of hematopoietic maturation events. Previous studies have suggested that the increased expression levels of homeobox (HOX)A genes was correlated with the cytogenetic findings associated with poor prognosis in acute myeloid leukemia and mixed lineage leukemia. The aim of the present study was to investigate the role of HOXA5 in leukemia. The U937 human leukemia cell line was transfected with a HOXA5‑targeted short hairpin RNA (shRNA) to determine the effects of downregulation of the HOXA5 on proliferation, apoptosis, cell cycle distribution and chemoresistance in leukemia cells. Reverse transcription‑quantitative polymerase chain reaction and western blot analyses demonstrated that the mRNA and protein expression levels of HOXA5 were markedly suppressed following transfection with an shRNA‑containing vector. Knockdown of HOXA5 significantly inhibited cell proliferation, as determined by Cell Counting kit‑8 assay. Flow cytometry revealed that reduced HOXA5 expression levels resulted in cell cycle arrest at the G1 phase, and induced apoptosis. In addition, western blot analysis demonstrated that HOXA5 knockdown increased the expression levels of caspase‑3, and reduced the expression levels of survivin in the U937 cells. Furthermore, knockdown of HOXA5 in the U937 cells enhanced their chemosensitivity to cytarabine. The results of the present study suggested that downregulation of HOXA5 by shRNA may trigger apoptosis and overcome drug resistance in leukemia cells. Therefore, HOXA5 may serve as a potential target for developing novel therapeutic strategies for leukemia.
- Subjects :
- Cancer Research
Antimetabolites, Antineoplastic
Biology
Biochemistry
Small hairpin RNA
Survivin
Genetics
medicine
Humans
RNA, Small Interfering
Molecular Biology
Transcription factor
Cell Proliferation
Homeodomain Proteins
Gene knockdown
Cytarabine
Myeloid leukemia
U937 Cells
Cell cycle
medicine.disease
Leukemia
homeobox A9
Leukemia, Myeloid, Acute
Oncology
Drug Resistance, Neoplasm
Cancer research
Molecular Medicine
RNA Interference
Subjects
Details
- ISSN :
- 17913004
- Volume :
- 12
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Molecular medicine reports
- Accession number :
- edsair.doi.dedup.....75890aefd966b4f50ced5f9cd05e389c