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HOXA9 is critical in the proliferation, differentiation, and malignancy of leukaemia cells both in vitro and in vivo
Author(s) -
Chen Shibing,
Yu Juan,
Lv Xin,
Zhang Lijuan
Publication year - 2017
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.3293
Subject(s) - gene silencing , cancer research , downregulation and upregulation , gene knockdown , in vivo , retinoic acid , differentiation therapy , biology , cell growth , tretinoin , cellular differentiation , microrna , cell culture , gene , genetics , acute promyelocytic leukemia
Progress in the understanding of the molecular mechanism for acute myeloid leukaemia is of great significance to generate new potential targets for treatment. Recent studies showed that HOXA9, a homeodomain‐containing transcription factor, is commonly deregulated in acute leukaemia. In this study, we elucidated the direct correlation between HoxA9 expression and progression of leukaemia using 2 different types of leukaemia cells HL‐60 and MOLT‐3. The HoxA9 expression level was decreased in leukaemia cells with the treatment of all‐trans retinoic acid or arsenic trioxide (As 2 O 3 ). Downregulation of HoxA9 could impair the proliferation and promote the leukaemia cell death. HoxA9 silencing also potentiated the differentiation of leukaemia cells, and in vivo studies demonstrated that HoxA9 downregulation could interfere the tumour growth. Interestingly, HoxA9 silencing also led to the alteration in miRNA expression, mediating the promoting effect on the leukaemia cell differentiation. Therefore, this work provided a promising and potentially efficient target to leukaemia treatment, indicating that HoxA9 is likely to be an ideal candidate in the gene therapy against acute myeloid leukaemia. In this study, we elucidated the critical role of HoxA9 in the proliferation and differentiation of leukaemia cells both in vitro and in vivo. The effect of HoxA9 modulation was correlated with the clinical effect of all‐trans retinoic acid and As 2 O 3 . Furthermore, HoxA9 also regulated the miRNA expression, controlling the leukaemia cell differentiation. Therefore, this work provided new insights into molecular mechanism underlying the leukaemia treatment, potentially putting forward a brand new target to the gene therapy against leukaemia.