Vol.:(0123456789) 1 3
Molecular Biology Reports
https://doi.org/10.1007/s11033-018-4416-0
ORIGINAL ARTICLE
Alleviating the progression of acute myeloid leukemia (AML)
by sulforaphane through controlling miR-155 levels
Mohsen Koolivand
1
· Maryam Ansari
3
· Fatemeh Piroozian
2
· Soheila Moein
1,4
· Kianoosh MalekZadeh
2,4
Received: 4 July 2018 / Accepted: 1 October 2018
© Springer Nature B.V. 2018
Abstract
Acute myeloid leukemia (AML) has the highest rate of mortality among the leukemias. Disruption in miRNAs level is
involved in the pathogenesis of the disease. The miR-155 has a role in primary diferentiation of myeloid progenitor.
Meanwhile, there is little knowledge about the efects of sulforaphane against leukemia. The present study tried to evaluate
pathologic efect of miR-155 in patients in various subgroups of AML, and then pioneered in assessing miR-155 levels by the
efect of sulforaphane in diferent AML cell lines. The miR-155 level was signifcantly higher in patients with AML compared
to the controls. Interestingly, the increase in miR-155 was converged with raising the subtype of AML (from M1 to M5).
The miR-155 levels increased by 1.2 times in patients with M1, but this increase reached 2.5 times in the patients in the M5
subgroup. Sulforaphane reduced the number of live cells and increased the mortality rate of AML cells particularly by induc-
tion of apoptosis. However, the anti-proliferative efect of this agent was more dominant and could dose-dependently lessen
miR-155 levels in myeloid leukemia cells. More or less, about 80% reduction in miR-155 expression was almost observed
after 48 h treatment with 60 µM sulforaphane in all four studied cell lines. The obtained results indicated that miR-155 might
function as an oncomir in AML and can potentially be considered as a prognosis biomarker for AML. The anti-cancer efects
of sulforaphane can be correlated with reduction of miR-155 levels. These fndings suggested that sulforaphane could induce
more diferentiation in myeloid progenitor cells through controlling the miR-155, thereby mitigating the progress of AML.
Keywords Sulforaphane · miR-155 · Acute myeloid leukemia · AML
Introduction
Acute myeloid leukemia (AML) is a malignancy in hemat-
opoietic progenitor cells. A clear characteristic of this dis-
ease is the loss of normal diferentiation and proliferation
of myeloid precursors [1, 2]. It is the most common acute
leukemia among adults and has the highest incidence of
mortality among diferent types of leukemia in the United
States, with an annual incidence of 3.7 per 100,000 people
[3]. Survival rates are low in patients with AML in compari-
son with other leukemias and almost one out of every four
adults will have a lifespan of more than 5 years [4].
Non-coding RNAs including microRNAs (miRNAs),
which play a key role in numerous pathological and physi-
ological pathways, regulate more than 30% of human pro-
tein-encoding genes [5]. MicroRNAs could be regulated and
transcribed independently [6]. Several studies have indicated
that any impairment in miRNAs levels could afect the reg-
ulation of cellular diferentiation, proliferation, division,
apoptosis, and other mechanisms, which consequently have
* Soheila Moein
soheila_9@yahoo.com
* Kianoosh MalekZadeh
keyanoosh@gmail.com; kianoosh.malekzadeh@hums.ac.ir
1
Department of Biochemistry, Faculty of Medicine,
Hormozgan University of Medical Sciences, Bandar Abbas,
Hormozgan, Iran
2
Department of Medical Genetic, Faculty of Medicine,
Hormozgan University of Medical Sciences, Bandar Abbas,
Iran
3
Department of Pathology, Faculty of Medicine, Hormozgan
University of Medical Sciences, Bandar Abbas, Hormozgan,
Iran
4
Hormozgan Institute of Health, Hormozgan University
of Medical Sciences, Bandar Abbas, Iran