TRIM25 contributes to the malignancy of acute myeloid leukemia and is negatively regulated by microRNA-137
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Open Medicine 2021; 16: 95–103
Research Article
Sheng Wang, Bang Shuo Zhang, Yi Yang, Ying Li, Jing Long Lv, Yu Cheng*
TRIM25 contributes to the malignancy of acute
myeloid leukemia and is negatively regulated
by microRNA-137
https://doi.org/10.1515/med-2021-0003 Keywords: TRIM25, acute myeloid leukemia, miR-137,
received July 17, 2020; accepted November 1, 2020 proliferation, metastasis
Abstract
Background ‒ Acute myeloid leukemia (AML) is a ubi-
quitous malignancy that occurs in the hematological
system. Tripartite motif-containing 25 (TRIM25) has been 1 Introduction
found to be involved in various carcinomas comprising
AML. However, the function and underlying causative Acute myeloid leukemia (AML) is the most common
role of TRIM25 in AML are still obscure. hematological malignancy in the world blood system
Methods and materials ‒ Quantitative real-time poly- characterized by the proliferation and infiltration of
merase chain reaction (qPCR) was used for assaying clonal, abnormally differentiated hemopoietic stem cells
TRIM25 and miR-137 expression in AML samples and in bone marrow, as well as peripheral blood, etc. [1]. AML
cells. CCK-8 assay, Calcein-acetoxymethylester/propidium is the most ubiquitous type of leukemia that occurs in
iodide staining, and Transwell assay were adopted to adults, and its global incidence is about 162/1 million,
assay cell proliferation, invasion, and migration. Dual- which increases with age [2,3]. Although AML has made
luciferase reporter experiment was used for analyzing good progress in diagnosis, treatment, and prognosis, its
the interaction of TRIM25 with miR-137. Western blot overall survival is still less than 50% [4]. Thus, it is urgent
was used for assaying protein expression levels. to explore further the pathogenesis of AML to seek for
Results ‒ This study confirmed that TRIM25 expression novel therapeutic strategies.
was upregulated in AML samples and cell lines, whereas Tripartite motif-containing 25 (TRIM25) is also called
miR-137 expression was downregulated. Overexpression estrogen-responsive finger protein, and the encoded TRIM25
of TRIM25 significantly contributed to AML cell’s prolif- protein belongs to the tripartite motif (TRIM) family [5].
eration, invasion, and migration, whereas knockdown Many TRIM family proteins harbor the function of E3
exerted the opposite effect. In addition, TRIM25 was a ligase [6]. Researches evidenced that the TRIM family
downstream target of miR-137 in AML cells and nega- has antiviral effects and actively participates in modu-
tively modulated by miR-137. lating cell differentiation, proliferation, apoptosis, and
Conclusion ‒ TRIM25 was targeted and regulated by tumorigenesis [7]. Studies have confirmed that the abnormal
miR-137, exerted a carcinogenic function in AML, and expression of TRIM25 is a crucial factor in the develop-
could be used as a latent biomarker and a treatment ment of carcinoma. For example, TRIM25 knockdown not
target for AML. only restrains prostate carcinoma cell proliferation but
also induces apoptosis via activating p53 protein [8].
The increased expression of TRIM25 in breast cancer is
related to unfavorable overall survival [9]. Overexpres-
* Corresponding author: Yu Cheng, Department of sion of TRIM25 contributes to lung carcinoma cell prolif-
Gastroenterology, Three Gorges Hospital Affiliated to Chongqing eration and migration [10]. Nonetheless, not only the role
University, No. 165 Xincheng Road, Wanzhou District, Chongqing, but also the potential mechanism of TRIM25 in AML is
404000, China, tel: +86-177-8209-6055,
currently indistinct.
e-mail: 174477594@qq.com
Sheng Wang, Bang Shuo Zhang, Yi Yang, Ying Li, Jing Long Lv:
MicroRNA (miRNA) is a type of small RNA without
Department of Hematology, Three Gorges Hospital Affiliated to coding function but has a length of 21–25 nucleotides. It
Chongqing University, Chongqing, 404000, China is a significant factor in gene modulation by suppressing
Open Access. © 2021 Sheng Wang et al., published by De Gruyter. This work is licensed under the Creative Commons Attribution 4.0
International License.
96 Sheng Wang et al.
the translation and degradation of target RNA [11]. 2.2 Cell culture and transfection
miRNAs have shown to modulate diverse biological signs
of progress, including differentiation, apoptosis, and pro- AML cell lines (HEL, Kasumi-1, HL-60, MEG01 cells) and
liferation [12]. The research found that miRNA is a sig- human bone marrow stromal cell line HS-5 were pur-
nificant factor in distinguishing normal blood cells [13]. chased from the Cell Bank of the Chinese Academy of
miRNA dysregulation can induce a variety of human dis- Sciences (Shanghai, China) and were cultivated in
eases. The abnormal expression of miRNA is closely con- DMEM (Invitrogen) comprising 10% FBS (Hyclone) and
nected to cancer progression, making it a latent marker antibiotics (100 U/mL penicillin and 100 mg/mL strepto-
for carcinoma prognosis and diagnosis [14]. miR-137 belongs mycin) (Hyclone) in a 5% CO2, 37°C, humidified incubator.
to the miRNA family and has been revealed to suppress miR-137 mimic (miR-137), mimic negative control
cancer in various cancers’ progress. For example, miR-137 (miR-con), miR-137 inhibitor (miR-137-in), negative inhi-
interferes with the interaction between BCL11A and DNMT1 bitor control (miR-in), small interfering RNA TRIM25
to inhibit the stemness and tumorigenesis of triple-negative (si-TRIM25#1, si-TRIM25#2, and si-TRIM25#3), negative
breast cancer cells [15]. miR-137 is inhibited by DNA hyper- control (si-NC), pcDNA3.0 (Vector), together with pcDNA-
methylation and exerts a carcinoma inhibition effect in TRIM25 (TRIM25) were the products of GenePharma
endometrial carcinoma [16]. Moreover, it was revealed that (Shanghai, China). The plasmids mentioned above or
miR-137 is reduced in AML, and the increase of miR-137 oligos were separately transfected into Kasumi-1 and
suppresses AML cell growth and metastasis [17]. Notwith- HL-60 cells that cultivated to logarithm stage, applying
standing, the specific causative role of miR-137 in the pro- Lipofectamine 2000 (Invitrogen, Shanghai, China). The
gress of AML has not been completely clarified, and therefore transfected cells were available for the subsequent
further research is still necessary. experiments.
This study explored the interaction between TRIM25
and miR-137 to reveal their potential mechanisms in
the malignant progression of AML. The results of our
research confirmed the upregulation of TRIM25 in AML.
Moreover, TRIM25 expression is negatively modulated by
2.3 Quantitative real-time polymerase chain
miR-137, which participates in facilitating AML cell’s pro- reaction (qPCR)
liferation, invasion, and migration.
According to (Invitrogen, Shanghai, China) instructions,
the total RNA from AML cells or samples was extracted
using TRIzol reagent. To detect TRIM25 mRNA expres-
2 Materials and methods sion, reverse transcription of the extracted RNA was per-
formed to obtain cDNA by PrimeScript One-step RT-PCR
kit (Takara). For miR-137 expression analysis, miScript
2.1 Clinical samples and patients reverse transcription kit (Qiagen) was adopted for synthe-
sizing cDNA from 50 ng of extracted RNA. SYBR Green
A total of 45 patients with AML (20 males and 25 females, Master Mix (Takara) was applied for assaying gene
50–72 years old, mean age 63.6 ± 5.1 years) and 45 expression levels. The relative expression was assessed
healthy volunteers who donate bone marrow were by adopting the 2−ΔΔCt method. β-Actin or U6 was recog-
regarded as normal controls (27 males and 18 females, nized as a standardized internal control. The synthesis of
50–72 years old, mean age 63.8 ± 5.3 years) who were PCR primers was completed (Sangon Biotech, China). The
admitted at the Three Gorges Hospital of Chongqing primer sequences are as follows: TRIM25 (forward 5′-GTC
University from January 2016 to June 2019. Investigation TCTACCCAGAACAGTTTCC-3′ and reverse 5′-ATCCAACAC
of the pathological and clinical follow-up data of the AGGCTGATTCC-3′); β-actin (forward 5′-ACTCGTCATACTC
patients was completed before the operation. Before using CTGCT-3′ and reverse 5′-GAAACTACCTTCAACTCC-3′);
these clinical samples, written informed consent was miR-137 (forward 5′-GCGCGCTTATTGCTTAAGAATAC-3′
obtained from the research subjects. The experiments and reverse 5′-GTCGTATCCAGTGCAGGGTCCGAGGTATTC
were approved by the Ethics Committee of the Three GCACTGGATACGACCTACGC-3′); and U6 (forward 5′-CTC
Gorges Hospital Affiliated to Chongqing University. All the GCTTCGGCAGCACA-3′ and reverse 5′-AACGCTTCACGAAT
patients provided written informed consent and the project TTGCGT-3′). Three repetitions of all experiments were
was in accordance with the Helsinki Declaration of 1975. completed, in triplicate.
TRIM25 effect on leukemia 97
2.4 Cell proliferation assay total protein. The protein samples (20 µg) were separated
using SDS-PAGE. Subsequently, the proteins were trans-
According to (Dojindo Molecular Technologies, Japan) ferred to PVDF (Millipore, Billerica, MA). The membrane
instructions, cell proliferation was assayed using CCK-8. was blocked in 5% skim milk at room temperature for 2 h,
In a word, the injection of cells was realized in 96-well and then incubated at 4°C with TRIM25 (Abcam) and
plates with 1 × 104 cells per well and then cultivated in β-actin (Abcam) overnight. After setting with HRP-linked
DMEM medium. At the end of the experiment, CCK-8 secondary antibody at room temperature for 1 h, the pro-
reagent (10 µL) was supplemented to the well. After incu- tein bands were visualized using an electrochemilumi-
bating for 2 h under 37°C conditions, the absorbance nescence kit (Pierce Biotechnology), adopting β-actin
measurement was accomplished at 450 nm using a protein as internal controls.
microplate reader.
2.8 Dual-luciferase reporters assay
2.5 Fluorescence cell viability assay
The 3′UTR sequence of TRIM25 was cloned into the pMIR
Cell viability was detected by Calcein-acetoxymethylester/ eukaryotic expression vector (Promega) containing the
propidium iodide (Calcein-AM/PI) Double Stain Kit luciferase gene for recovery, digestion, and purification
(American Type Culture Collection, VA, USA). Then 5 µL to construct the pMIR-TRIM25-WT plasmid. Similarly, the
of Calcein-AM solution (2 mM) and 15 µL of PI solution pMIR-TRIM25-MUT plasmid was also built. Based on the
(1.5 mM) were added to 5 mL of 1× Assay Buffer. As a manufacturer’s protocol, HL-60 cells were co-transfected
result, the working solution concentration of Calcein- with WT or MUT and miR-137 mimics or miR-con apply-
AM/PI was 2 and 4.5 µM respectively. The cells were later ing Lipofectamine 2000 reagent. Luciferase activity was
incubated for 15 min at 37°C. Photographs were taken assayed using the luciferase assay system (Promega) and
using the fluorescence microscope. was standardized to Renilla.
2.6 Cell migration and invasion assay 2.9 Statistical analysis
Matrigel-coated Transwell and Transwell inserts (Corning, All the data were analyzed by GraphPad Prism 8.0 and
MA, USA) were applied for assaying the invasion and SPSS statistical and presented as mean ± standard error
migration of AML cells. In brief, in 200 µL of serum-free (SD) from at least three individual experiments. Student’s
medium, Kasumi-1 and HL-60 cells with a density of 2 × t-test and one-way analysis of variance were applied to
104 cells were added, either covered or not covered with analyze the significance differences. Linear correlation
Matrigel. Then, the cell plate was incubated under 5% between miR-137 and TRIM25 was calculated by Pearson’s
CO2, 37°C, humidified environment. After cultivating for correlation test. P < 0.05 was considered as statistically
24 h (migration test) or 48 h (invasion test), the upper significant.
chamber cells were mildly wiped off using a cotton
swab. In the lower chamber, migrating or invading cells
were fixed using alcohol for 15 min and stained using
crystal violet for 10 min. Finally, the cells were counted 3 Results
using an optical microscope (Olympus, Tokyo, Japan)
at 200×.
3.1 The expression characteristics of
TRIM25 in AML
2.7 Western blot To explore TRIM25 expression in AML, we first retrieved
TRIM25 expression in the TCGA-AML sample through the
According to the supplier’s instructions, RIPA lysis buffer GEPIA database (http://gepia.cancer-pku.cn/). As shown
(Beyotime) was used to isolate AML samples and cells’ in Figure 1a, TRIM25 was significantly upregulated in the
98 Sheng Wang et al.
AML samples. Subsequently, qPCR was applied for assay- 3.2 TRIM25 facilitated the AML cell’s
ing the TRIM25 mRNA level in the blood samples of 45 proliferation, migration, and invasion
patients with AML and 45 healthy volunteers. It was
discovered that the TRIM25 mRNA level in samples of To study the impact of TRIM25 on the malignant progres-
patients with AML was strikingly upregulated in contrast sion of AML, we transfected TRIM25 siRNAs in Kasumi-1
to normal controls (Figure 1b). qPCR and western blot cells with the highest TRIM25 expression to construct
manifested that TRIM25 mRNA and protein expressions a TRIM25 knockdown cell model, and transfect TRIM25
in AML cell lines were noteworthily higher than that of in HL-60 cells with the lowest TRIM25 expression. The
HS-5 cells (Figure 1c and d). expression plasmid was used to build a cell model of
Moreover, we also searched the GEPIA database to TRIM25 overexpression, and the transfection effect of
understand the association of the high TRIM25 expres- the cells was assayed with qPCR. TRIM25 expression in
sion in AML with the patient’s prognosis. As a result, Kasumi-1 cells transfected with TRIM25 siRNAs was reduced,
patients with AML with highly expressed TRIM25 har- whereas TRIM25 expression was observably upregulated in
bored shorter overall survival than those with low expressed HL-60 cells transfected with TRIM25 overexpression plas-
TRIM25 (Figure 1e). All the above results implicated that mids (Figure 2a). Western blot analysis of TRIM25 protein
TRIM25 plays a carcinogenic role in AML and can be showed that siRNA silencing markedly reduced TRIM25 pro-
used as a potential marker of unfavorable prognosis tein expression, and TRIM25 expression construct signifi-
in AML. cantly increased TRIM25 protein (Figure 2b). We further
Figure 1: TRIM25 was highly expressed in AML samples and cells and was related to poor prognosis. (a) GEPIA database to retrieve
TRIM25 expression in AML. (b) qPCR to assay TRIM25 mRNA expression in samples from 45 patients with AML and 45 healthy
volunteers. (c and d) Western blot and qPCR to determine TRIM25 protein and mRNA expression in AML cells and HS-5 cells.
(e) GEPIA database to analyze the correlation between the expression level of TRIM25 and the prognosis of patients with AML.
*P < 0.05, **P < 0.01, ***P < 0.001.TRIM25 effect on leukemia 99 Figure 2: TRIM25 promoted the proliferation, migration, and invasion of AML cells. (a) qPCR to detect TRIM25 mRNA expression in Kasumi-1 and HL-60 cells after knocking down or overexpressing TRIM25. (b) Western blot analysis of TRIM25 protein expression in cells transfected with miR-137 mimics or inhibitor. (c) CCK-8 assay to detect the proliferation of AML cells after knocking down or overexpressing TRIM25. (d) Cell viability was tested using live (calcein staining, green)/dead (PI staining, red) assay. Scale bar = 100 µm. (e and f). Transwell test to detect the migration and invasion of AML cells after knocking down or overexpressing TRIM25. *P < 0.05, **P < 0.01, ***P < 0.001. used the CCK-8 experiment, Calcein-AM/PI double staining, 3.3 TRIM25 was a downstream target of and the Transwell experiment to detect cell proliferation, miR-137 migration, and invasion. Consequently, knocking down TRIM25 significantly inhibited the invasion, migration, and To further clarify the potential causative role of TRIM25 in proliferation of Kasumi-1 cells compared to the control the progress of AML, bioinformatics analysis was carried group, whereas overexpression of TRIM25 significantly pro- out to predict the miRNA targets of TRIM25 using starBase moted the invasion, migration, and proliferation of HL-60 (http://starbase.sysu.edu.cn/) and miRanda (http://www. cells (Figure 2c–f). The above certificated that TRIM25 exerts microrna.org/). Among these miRNAs, miR-137, which is a a carcinogenic function in the progress of AML via facili- tumor-suppressive miRNA in various cancers, attracted our tating the AML cell’s proliferation, invasion, and migration. interest. We verified the presence of a base complementary
100 Sheng Wang et al.
Figure 3: TRIM25 was the target of miR-137. (a) Bioinformatics analysis predicted the binding sequence of miR-137 and TRIM25. (b) Dual-
luciferase reporter experiment to analyze the binding relationship between miR-137 and TRIM25. (c and d) Western blot and qPCR to detect
the effect of knockdown or overexpression of miR-137 on TRIM25 protein and mRNA expression. (e and f) qPCR to detect miR-137 expression
in AML samples and cells. (g) qPCR to evaluate the correlation between miR-137 and TRIM25 mRNA expression in AML samples. **P < 0.01,
***P < 0.001.
binding site of miR-137 with TRIM25 (Figure 3a). We further mimics in HL-60 cells or transfect miR-137 + TRIM25,
adopted a dual-luciferase reporter experiment for assaying and used qPCR to detect the efficiency of cell transfection
the targeting association of TRIM25 with miR-137. As a (Figure 4a). Further, AML cell’s proliferation, invasion,
result, overexpression of miR-137 visibly reduced wild- and migration were assayed adopting the CCK-8 assay,
type TRIM25 luciferase activity but harbored no critical Calcein-AM/PI double staining, and Transwell assay.
influence on the luciferase activity of mutant TRIM25 Consequently, in contrast to the control group, miR-137
(Figure 3b). Western blot and qPCR exhibited that miR- knockdown facilitated AML cell’s invasion, migration,
137 knockdown increased TRIM25 protein and mRNA and proliferation, whereas the downregulation of TRIM25
expression, whereas overexpression of miR-137 inhibited attenuated this promotion effect (Figure 4b–f). On the
TRIM25 mRNA and protein expression (Figure 3c and d). contrary, overexpressed miR-137 notably suppressed HL-
Besides, qPCR was used for assaying miR-137 expression in 60 cells invasion, migration, and proliferation, and this
AML cells and blood samples. The results revealed signifi- inhibitory effect was remarkably reversed by overex-
cantly downregulated miR-137 in AML cell lines and blood pressed TRIM25 (Figure 4b–g). These outcomes impli-
samples (Figure 3e and f). TRIM25 mRNA level in AML cated that miR-137 suppresses AML cell’s migration, inva-
blood samples harbored a negative association with miR- sion, and proliferation via modulating TRIM25.
137 (Figure 3g). These consequences implied that TRIM25 is
the target of miR-137 in AML cells, and the negative feed-
back of miR-137 regulates its expression.
4 Discussion
The low early diagnosis rate, the fast progress, and poor
3.4 miR-137 restrained AML cell’s invasion, curative effect result in an unfavorable prognosis of
migration, and proliferation by patients with AML [18,19]. Therefore, exploring the bio-
modulating TRIM25 logical mechanism of how AML develops is imperative.
In this work, we evidenced that TRIM25 is upregulated
To clarify the mechanism of action of miR-137 in AML, we in AML. The miR-137/TRIM26 axis regulated AML cell’s
transfected Kasumi-1 cells with miR-137 inhibitors or co- invasion, migration, and proliferation, promising new
transfected with si-TRIM25#1, and transfected miR-137 latent treatment strategies for patients with AML.TRIM25 effect on leukemia 101
Figure 4: miR-137 inhibited AML cell’s proliferation and migration by targeting TRIM25. (a) qPCR to detect TRIM25 mRNA expression in
Kasumi-1 cells transfected with miR-137 inhibitor or co-transfected with si-TRIM25#1 and HL-60 cells transfected with miR-137 mimics or
co-transfected with TRIM25. (b) CCK-8 assay was performed to detect cell proliferation. (c) Cell viability was visualized by staining the
cytoplasm with a live cell indicator, Calcein-AM (green). Scale bar = 100 µm. (d–g) Transwell assay to detect cell migration and invasion.
*P < 0.05, **P < 0.01, ***P < 0.001.
TRIM25, which belongs to the TRIM protein family, differentiation, and proliferation [7]. Furthermore,
has RBCC multi-domains, encompassing RING, coiled- increasing research evidence shows that TRIM family
coil, and B-box. As E3 ligase, it can be combined with proteins are essential regulators of tumorigenesis and
substrate protein to make it ubiquitinated/ubiquitin- development and play crucial functions in the biological
like degradation or modification, thereby regulating the signs of progress comprising tumor cell differentiation,
biological function process [5–7]. Many studies have proliferation, apoptosis, invasion, and migration, among
shown that the TRIM family has antiviral effects and which TRIM19, TRIM24, TRIM33, and TRIM2 mainly obtain
actively participates in the modulation of cell apoptosis, the oncogene characteristics through chromosomal102 Sheng Wang et al.
rearrangement [6], TRIM27 downregulates its tumor-sup- Studies revealed that miRNA is capable of playing a
pressive effect by mediating the atypical ubiquitination critical part in cancer progression by regulating TRIM25.
of the tumor suppressor gene PTEN [20]. Studies have For example, miR-365 restrains non-small cell lung car-
shown that TRIM25 can be used as a transcription factor cinoma’s progress by suppressing TRIM25 expression
to regulate cellular biological processes and exert a car- [30]. Overexpressed miR-3614-3p inhibits the growth of
cinogenic function in carcinoma progress. For instance, breast carcinoma cells via downregulating TRIM25 [31]. It
TRIM25 is markedly overexpressed in gastric carcinoma, is worth mentioning that this study found the existence of
and TRIM25 knockdown suppresses the migration and a binding site of TRIM25 with miR-137 using bioinfor-
invasion of gastric carcinoma cells via the TGF-β signal matics analysis. Given previous research, we speculate
[21]. TRIM25 contributes to the survival and the growth of that miR-137 likely plays a part as an upstream molecule
hepatoma cells via targeting the Keap1-Nrf2 pathway, of TRIM25 in AML. In the dual-luciferase reporter experi-
and highly expressed TRIM25 predicts the unfavorable ment, we showed that miR-137 is capable of directly
prognosis of patients with liver carcinoma [22]. In this binding to TRIM25, and the two expressions harbored a
study, we confirmed the cancer-promoting role of TRIM25 negative correlation in AML blood samples. In addition,
in AML and found that TRIM25 is overexpressed in AML knocking down TRIM25 attenuated the promotion of
blood samples and cells. AML cell’s invasion, migration, and proliferation because
Further functional experiments confirmed that knock- of silencing miR-137. On the contrary, overexpression of
ing down TRIM25 suppressed AML cells’ prolifera- TRIM25 significantly reversed the suppressive impact of
tion, invasion, and migration, whereas overexpressed overexpression of miR-137 on AML cell’s migration, inva-
RIM25 facilitates cell invasion, migration, and prolif- sion, and proliferation, indicating that miR-137 can target
eration. In addition, the high TRIM25 expression was TRIM25 to regulate AML cell’s proliferation, invasion, and
distinctly concerned with the unfavorable prognosis of migration.
patients with AML. These findings implicated that To conclude, our study evidenced highly expressed
TRIM25 could participate in the progression of AML TRIM25 in AML blood samples and cells, which is con-
as a carcinogen. cerned with the unfavorable prognosis of patients with
Some studies have found that miRNA is a significant AML. Besides, we confirmed that the miR-137/TRIM25
factor in diverse physiological progress encompassing axis takes part in modulating AML’s cell invasion, migra-
cell differentiation, apoptosis, and proliferation [23]. It tion, and proliferation. This study reveals new potential
is often dysregulated in various human tumors and molecular mechanisms in the progress of AML and pro-
is closely connected to tumor advancement [24]. The vides an original rationale for clinically diagnosing and
research found a certain level of miRNA in human serum, treating AML.
and the change of miRNA expression profile in serum has
a clear correlation with the progress of various tumors Funding statement: This study was supported in part by
[25,26]. Substantial studies have confirmed that miRNA grants from the Wanzhou District Kewei Joint Medical
exerts a crucial regulatory function in tumor progress research project (grant no. wzstc-kw2020014).
(including AML) and participates in inhibiting or pro-
moting tumors’ malignant progression. For example, Conflict of interest: The authors declared no potential
miR-34c-5p inhibits exosome shedding via selectively conflicts of interest with respect to the research, author-
targeting RAB27B, induces AML cell senescence, and pro- ship, and/or publication of this article.
motes the elimination of AML stem cells [27]. miR-34a
contributes to AML cell apoptosis and restrains auto- Data availability statement: The data used to support the
phagy via targeting HMGB1 [28]. miR-485-5p suppresses findings of this study are available from the correspond-
the AML cell proliferation via targeting SALL4 [29]. In ing author upon request.
this work, we evidenced significantly downregulated
miR-137 in AML blood samples as well as cells. In vitro
cell function experiments confirmed that knocking down
miR-137 significantly raised AML cell’s invasion, migra-
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