Interplay between mitochondrial dysfunction and lysosomal storage: challenges in genetic metabolic muscle diseases with a focus on infantile onset Pompe disease.

Background: Pompe disease (PD) is a rare, progressive autosomal recessive lysosomal storage disorder that directly impacts mitochondrial function, leading to structural abnormalities and potentially culminating in heart failure or cardiogenic shock. The clinical course and molecular mechanisms of the disease remain incompletely understood. Methods: We performed a retrospective analysis to examine the clinical manifestations, genetic traits, and the relationship between PD and mitochondrial function in a pediatric patient. This comprehensive evaluation included the use of ultrasound echocardiograms, computed tomography (CT) scans, electrocardiograms, mutagenesis analysis, and structural analysis to gain insights into the patient's condition and the underlying mechanisms of PD. For structural analysis and visualization, the structure of protein data bank ID 5KZX of human GAA was used, and VMD software was used for visualization and analysis. Results: The study revealed that a 5-month-old male infant was admitted due to fever, with physical examination finding abnormal cardiopulmonary function and hepatomegaly. Laboratory tests and echocardiography confirmed heart failure and hypertrophic cardiomyopathy. Despite a week of treatment, which normalized body temperature and reduced pulmonary inflammation, cardiac abnormalities did not show significant improvement. Further genetic testing identified a homozygous mutation c.2662G>T (p.E888) in the GAA gene, leading to a diagnosis of Infantile-Onset Pompe Disease (IOPD). Conclusions: Although enzyme replacement therapy can significantly improve the quality of life for patients with PD, enhancing mitochondrial function may represent a new therapeutic strategy for treating PD.

[Effect of polydatin on the proliferation and apoptosis of THP-1 cells and the mechanism]. / 虎杖苷对THP-1ç»†èƒžå¢žæ®–åŠå‡‹äº¡çš„å½±å“åŠå ¶ä½œç”¨æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To explore the effect of polydatin on the proliferation and apoptosis of acute monocytic leukemia cell line THP-1 and the possible mechanism. METHODS: After THP-1 cells were treated with polydatin at gradient concentrations for 24 hours and 48 hours, their proliferation was determined by CCK-8 assay, and half maximal inhibitory concentration (IC50) was calculated. Logarithmically growing THP-1 cells were divided into two groups, a polydatin treatment group (treated with IC50 of polydatin) and a blank control group (treated without polydatin solution), and incubated for 48 hours. Cell apoptosis and cell cycle were measured by flow cytometry. The expression levels of PI3K, AKT, p-AKT, mTOR, p-mTOR, p70 S6K, and p-p70 S6K proteins were measured by Western blotting. RESULTS: After treatment with polydatin, the proliferation of THP-1 cells was strongly inhibited, and the IC50 at 48 hours was 1 800 µmol/L. After treatment with 1 800 µmol/L polydatin solution for 48 hours, the apoptosis rate of THP-1 cells increased significantly compared with the blank control group (P<0.05). The cell cycle was arrested in the G0/G1 and S phases, with a significantly increased proportion of cells in the G0/G1 phase and a significantly decreased proportion of cells in the S phase, as compared with the blank control group (P<0.05). The expression levels of PI3K, AKT, p-AKT, mTOR, p-mTOR, p70 S6K, and p-p70 S6K proteins decreased significantly compared with the blank control group (P<0.05). CONCLUSIONS: Polydatin can effectively inhibit the proliferation, block the cell cycle, and induce the apoptosis of THP-1 cells, which may be related to inhibition of the PI3K/AKT/mTOR signaling pathway.

[Analysis of clinical features and FKTN gene variant in a child with congenital muscular dystrophy].

OBJECTIVE: To analyze the clinical features and genetic basis for a child featuring elevated creatine kinase (CK). METHODS: Next-generation sequencing (muscular dystrophy related gene panel) was carried out for the proband. Candidate variants were verified by Sanger sequencing of the child and his parents. RESULTS: The child was found to harbor compound heterozygous variants of the FKTN gene, including a missense c.536G>C (p.R179T) variant from his father and a non-frameshift c.1299_1301delGTG (p.W434del) variant from his mother. Both variants were predicted to be pathogenic. CONCLUSION: The compound heterozygous variants of the FKTN gene probably underlay the disease in this child. Above finding has expanded the mutation spectrum of congenital muscular dystrophy.

MAGI2-AS3 restrains proliferation, glycolysis, and triggers apoptosis in acute lymphoblastic leukemia via regulating miR-452-5p/FOXN3 pathway.

Objectives: MAGI2-AS3 is a cancer suppressor gene of multiple malignancies. Acute lymphoblastic leukemia (ALL) is an important type of leukemia that especially occurs in children. Our work evaluated the modulation of MAGI2-AS3 in ALL. Materials and Methods: qPCR and Western blotting were adopted for detection of target molecular expression. Growth and apoptosis were determined by CCK8 assay and Annexin V/PI staining. Glycolysis was detected by commercial kits. The direct binding between miR-452-5p and MAGI2-AS3 or FOXN3 was assessed by luciferase reporter assay. Tumor growth was measured in nude mice in vivo. Results: MAGI2-AS3 was down-regulated in ALL. Enforced expression of MAGI2-AS3 inhibited growth and glycolysis while promoting apoptosis of ALL cells. Moreover, MAGI2-AS3 up-regulated FOXN3 via sponging miR-452-5p. FOXN3 depletion abrogated MAGI2-AS3-mediated anti-cancer action. More importantly, MAGI2-AS3 repressed ALL cell growth in nude mice through regulation of miR-452-5p/FOXN3. Conclusion: MAGI2-AS3 inhibits ALL development via modulating miR-452-5p/FOXN3.

Triclosan targets miR-144 abnormal expression to induce neurodevelopmental toxicity mediated by activating PKC/MAPK signaling pathway.

Although the previous research confirmed that triclosan (TCS) induced an estrogen effect by acting on a novel G-protein coupled estrogen-membrane receptor (GPER), the underlying mechanisms by which downstream pathways induce neurotoxicity remain unclear after TCS activation of GPER. By employing a series of techniques (Illumina miRNA-seq, RT-qPCR, and artificial intervention of miRNA expression), we screened out four important miRNAs, whose target genes were directly/indirectly involved in neurodevelopment and neurobehavior. Especially, the miR-144 up-regulation caused vascular malformation and severely affected hair-cell development and lateral-line-neuromast formation, thereby causing abnormal motor behavior. After microinjecting 1-2-cell embryos, the similar phenotypic malformations as those induced by TCS were observed, including aberrant neuromast, cuticular-plate development and motor behavior. By KEGG pathway enrichment analysis, these target genes were demonstrated to be mainly related to the PKC/MAPK signaling pathway. When a PKC inhibitor was used to suppress the PKC/MAPK pathway, a substantial alleviation of TCS-induced neurotoxicity was observed. Therefore, TCS acts on GPER to activate the downstream PKC/MAPK signaling pathway, further up-regulating miR-144 expression and causing abnormal modulation of these nerve-related genes to trigger neurodevelopmental toxicity. These findings unravel the molecular mechanisms of TCS-induced neurodegenerative diseases, and offer theoretical guidance for TCS-pollution early warning and management.

Induction of lipid metabolism dysfunction, oxidative stress and inflammation response by tris(1-chloro-2-propyl)phosphate in larval/adult zebrafish.

As an important organophosphate flame retardant, tris(1-chloro-2-propyl)phosphate (TCPP) is ubiquitous in the environment leading to inevitable human exposure. However, there is a paucity of information regarding its acute/chronic effects on obesity, lipid homeostasis, and hepatocellular carcinoma, especially regarding the underlying molecular mechanisms in humans. Herein, we investigated the effects of TCPP exposure (5-25 mg/L) on lipid homeostasis in larval and adult zebrafish (Danio rerio). TCPP exposure caused remarkable lipid-metabolism dysfunction, which was reflected in obesity and excessive lipid accumulation in zebrafish liver. Mechanistically, TCPP induced the over-expression of adipogenesis genes and suppressed the expression of fatty-acid ß-oxidation genes. Consequently, excess lipid synthesis and deficient expenditure triggered oxidative damage and an inflammation response by disrupting the antioxidant system and over-expressing proinflammatory cytokine. Based on high-throughput transcriptome sequencing, we found that TCPP exposure led to enrichment of several pathways involved in lipid metabolism and inflammation, as well as several genes related to pathways of cancer. Notably, increasing expressions of Ki-67 and 53BP1 proteins, which are reliable biomarkers for recognition and risk prediction of cellular proliferation in cancer cells, were observed in liver tissues of adult zebrafish. These results imply that chronic TCPP exposure triggers a potential risk of hepatocellular carcinogenesis (HCC) progression. Collectively, these findings offer new insights into our mechanistic understanding for the health effects of organophosphorus flame retardants on humans.

Oncogenic Long Noncoding RNA DARS-AS1 in Childhood Acute Myeloid Leukemia by Binding to microRNA-425.

OBJECTIVE: Acute myeloid leukemia (AML) represents a hematological cancer. The aim of the investigation was to probe the regulatory relevance of long non-coding RNA (lncRNA) aspartyl-tRNA synthetase anti-sense 1 (DARS-AS1)/microRNA-425 (miR-425)/transforming growth factor-beta 1 (TGFB1) to the development of AML. METHODS: The DARS-AS1 expression in bone marrow tissues was first analyzed in healthy subjects and AML patients. Subsequently, AML cell lines with DARS-AS1 knockdown were constructed, followed by cell proliferation and apoptosis assays. Afterward, downstream miRNA of DARS-AS1 and target mRNA of the miRNA were analyzed by bioinformatics, and their binding relationships were verified. Functional rescue experiments were then implemented. Finally, activation of the Smad2/3 signaling in MV4-11 and BF-24 cells were detected by western blot. RESULTS: DARS-AS1 was overexpressed in bone marrow tissues of AML patients and cells, and DARS-AS1 knockdown suppressed the proliferation of AML cells and induced apoptosis. DARS-AS1 bound to and negatively correlated with miR-425. Further results suggested that TGFB1 might be a target gene of miR-425 and could promote Smad2/3 phosphorylation and nuclear translocation. Finally, DARS-AS1 depletion could diminish the tumor volume in vivo. CONCLUSION: All in all, we highlighted here that DARS-AS1 enhanced the expression of TGFB1 through binding to miR-425 to modulate AML progression via the Smad2/3 pathway, which might perform as a therapeutic target for AML.

Increased serum total bilirubin-albumin ratio was associated with bilirubin encephalopathy in neonates.

We performed the present study to summarize the recent epidemiological characteristics of bilirubin encephalopathy and assess the role of total bilirubin-albumin ratio in the bilirubin encephalopathy. We retrospectively collected clinical data of 669 neonates with hyperbilirubinemia from the First Affiliated Hospital of Zhengzhou University between January 2015 and July 2018, including 153 neonates belonged to bilirubin encephalopathy and 516 ones were treated as control group. Compared with the control group, those with bilirubin encephalopathy have higher bilirubin-albumin ratio (13.8 ± 3.6 vs. 10.6 ± 2.5, P=0.000). The direct bilirubin and indirect bilirubin level were higher in the case group than that in the control group (P=0.000). On the contrary, the hemoglobin level was lower in the case group than that in the control group (P=0.004). There were no significant differences in gestational age (P=0.510), gender rate (P=0.313), maternal gestational diabetes ratio (P=0.071), natural childbirth ratio (P=0.686), and meconium delay (P=0.091). The results from univariate regression indicated the total bilirubin/albumin ratio was positively associated with bilirubin encephalopathy (odds ratio (OR) = 1.67, 95% confidence interval (CI): 1.59-3.14). The total bilirubin, direct bilirubin, and indirect bilirubin were also related to encephalopathy. After adjusting some potential cofounding factors, the total bilirubin-albumin was still associated with bilirubin encephalopathy. The higher total bilirubin-albumin ratio increased the risk of bilirubin encephalopathy by 23% (OR = 1.23, 95% CI: 1.16-2.48). Our results indicated that the bilirubin-albumin ratio is associated with bilirubin encephalopathy in neonates, and could be a potential predictor.

miR-34a inhibits progression of neuroblastoma by targeting autophagy-related gene 5.

Neuroblastoma (NB) is a common pediatric malignancy with high mortality in childhood. Although many attentions have been gained, novel biomarkers for NB diagnosis and prognosis are still needed. microRNAs (miRNAs) played important roles in NB progression and miR-34a is a tumor suppressor in NB. However, the mechanism that underlies miR-34a regulating proliferation, migration, invasion and autophagy in NB remains poorly understood. In this study, cell proliferation was investigated by MTT and colony assay. Cell apoptosis was measured by caspase 3 activity assay. Cell migration and invasion were detected by trans-well analysis. Autophagy was measured via GFP-LC3 puncta fluorescence assay and western blots (WB). The expression of miR-34a was examined by quantitative real-time PCR (qRT-PCR). The regulatory effect of miR-34a on autophagy-related gene 5 (ATG5) was detected by qRT-PCR and WB. The interaction between miR-34a and ATG5 was probed by luciferase activity and RNA immunoprecipitation (RIP) assay. Results showed that miR-34a expression was inhibited in NB tissues and cells with low survival rate. Addition of miR-34a suppressed cell proliferation, migration, invasion and autophagy but promoted apoptosis in NB cells, whereas miR-34a deficiency played opposite roles in NB progression. Intriguingly, ATG5 was directly targeted by miR-34a. Moreover, ATG5 restoration attenuated miR-34a-mediated inhibitory effect on proliferation, apoptosis, migration, invasion and autophagy. These results indicated miR-34a suppressed proliferation, apoptosis, migration, invasion and autophagy in NB cells by targeting ATG5, providing a novel therapeutic avenue for NB treatment.

YKL-40 levels are associated with disease severity and prognosis of viral pneumonia, but not available in bacterial pneumonia in children.

BACKGROUND: Viral pneumonia is the main type of community-acquired pneumonia (CAP) in children. YKL-40, a chitinase-like protein, is regarded as a biomarker of the degree of inflammation. METHODS: Children who were diagnosed with CAP, including viral pneumonia, bacterial pneumonia, and dual infection, were included in the cohort study. The pathogenic diagnosis depended on PCR and immunoassay test. YKL-40 levels were examined twice by enzyme-linked immunoassay (ELISA). RESULTS: Serum YKL-40 levels were higher in patients with pneumonia than in healthy controls. The admission levels of YKL-40 in serum and Bronchoalveolar lavage (BALFs) indicated a positive correlation with the serum levels of C-reactive protein and other inflammatory cytokines (IL-6 and TNF-α). The disease severity have no correlation with the admission serum levels of YKL-40. Meanwhile, reductions in YKL-40 levels from initial admission levels to day 5 post-admission were correlated with disease severity. The multiple logistic analysis indicated the decreased extent of serum YKL-40 level as an independent prognostic predictor of severe cases in patients with viral pneumonia. CONCLUSIONS: Reductions in serum YKL-40 levels on day 5 after receiving therapy is a possible prognostic biomarker for children with viral pneumonia.

Lymphoma associated hemophagocytic syndrome: A single-center retrospective study.

To improve the understanding of lymphoma associated hemophagocytic syndrome (LAHS) and find an effective treatment for this fatal disease, 57 patients with LAHS were retrospectively reviewed. The most common histopathological type was extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKL) (45.61%). Patients with B-cell LAHS were significantly older (P<0.001), and exhibited a higher triglyceride level (P=0.012), lower serum ferritin level (P=0.014) and lower plasma Epstein-Barr virus DNA (P<0.001) compared with patients with T/NK-cell LAHS. The median survival time of all patients was 43 days, and patients with B-cell (n=14) and T/NK-cell (n=43) LAHS had a median survival time of 55 and 40 days, respectively (P=0.797). Compared with patients who were treated based on HLH-2004 protocols combined with multidrug chemotherapy, those without chemotherapy had a reduced prognosis (P=0.002). The patients that underwent hematopoietic stem cell transplantation (HSCT) following chemotherapy had a significantly improved overall survival (OS) compared with patients that did not undergo HSCT (P=0.001). Patients with B-cell LAHS treated with rituximab (P=0.015) and patients with ENKL treated with L-asparaginase/pegaspargase (L-asp/peg) (P=0.009) had an improved prognosis compared with patients not treated with these drugs. In the T/NK-cell LAHS group, patients treated with chemotherapy containing gemcitabine did not exhibit an improved OS compared with those not treated with gemcitabine (P=0.326). Furthermore, multivariate analysis demonstrated that long diagnosis time and poor performance status were independent prognosis factors for all patients with LAHS. The present study indicated that survival time does not differ between patients with B-cell LAHS and patients with T/NK-cell LAHS. Early diagnosis and appropriate immunochemotherapy plus HSCT are essential to achieve improved outcomes. The outcome of patients with B-cell LAHS may be significantly improved following treatment with rituximab. L-asp/peg-containing regimens are promising treatments for patients with NK/T-cell LAHS.

[Clinical features and prognosis of malignancy-associated hemophagocytic lymphohistiocytosis in children: a clinical analysis of 24 cases].

OBJECTIVE: To investigate the clinical features and prognosis of malignancy-associated hemophagocytic lymphohistiocytosis (MAHS) in children. METHODS: A retrospective analysis was performed for the primary diseases, clinical features, and prognosis of 24 children with MAHS. RESULTS: Among the 24 children, 11 (46%) had MAHS induced by tumor and 13 (54%) had chemotherapy-associated MAHS. As for primary diseases, 17 children had acute leukemia, 6 had lymphoma, and 1 had neuroblastoma. The most common clinical manifestations were pyrexia, respiratory symptoms, and hepatosplenomegaly. The most common laboratory abnormalities were hemocytopenia, elevated serum ferritin, and elevated lactate dehydrogenase. Of the 24 children, 22 were treated according to the HLH-2004 protocol and 2 gave up treatment; 18 children died, 1 was lost to follow-up, and 5 survived. The survival time ranged from 3 days to 2 years and 4 months (median 28 days). CONCLUSIONS: Children with MAHS have various clinical features and extremely poor treatment outcomes.

Utility of baseline, interim and end-of-treatment 18F-FDG PET/CT in extranodal natural killer/T-cell lymphoma patients treated with L-asparaginase/pegaspargase.

Positron emission tomography-computed tomography (PET/CT) is widely used for initial staging and monitoring treatment responses in Hodgkin and diffuse large B-cell lymphoma. However, its prognostic value in extranodal natural killer (NK)/T-cell lymphoma (ENKL) remains unclear. Here, we conducted a retrospective study to determine the impact of PET/CT in ENKL. Fifty-two patients newly diagnosed with ENKL were enrolled. Baseline maximum standardized uptake values (SUVmax), whole-body metabolic tumor volume (WBMTV) and whole-body total lesion glycolysis (WBTLG) were recorded. Additionally, interim PET/CT (I-PET) and end-of-treatment PET/CT (E-PET) results were scored using a 5-point scale. Patients were divided into groups using baseline parameter cut-off values; significant differences were found in overall survival (OS) and progression-free survival (PFS) between the high and low WBMTV and WBTLG groups and in OS between the two SUVmax groups. Positive I-PET and E-PET results predicted inferior PFS and OS. A multivariate analysis showed that baseline WBTLG, I-PET and E-PET results were associated with PFS and OS, and baseline SUVmax was an independent predictor of OS. Thus, baseline WBTLG, I-PET and E-PET results are good predictors of PFS and OS in ENKL patients who received L-asparaginase/pegaspargase in their first-line treatment, and baseline SUVmax is a valuable tool for assessing OS.

Clinical Efficacy of Therapy with Recombinant Human Interferon α1b in Hand, Foot, and Mouth Disease with Enterovirus 71 Infection.

UNLABELLED: A rapid expansion of HFMD with enterovirus 71 infection outbreaks has occurred and caused deaths in recent years in China, but no vaccine or antiviral drug is currently available for EV71 infection. This study aims to provide treatment programs for HFMD patients. We conducted a randomized, double-blind, controlled trial and evaluated clinical efficacy of therapy with rHuIFN-α1b in HFMD patients with EV71 infection. There were statistical differences in outcomes including the fever clearance time, healing time of typical skin or oral mucosa lesions, and EV71 viral load of the HFMD patients among ultrasonic aerosol inhalation group, intramuscular injection group and control group. rHuIFN-α1b therapy reduced the fever clearance time, healing time of typical skin or oral mucosa lesions, and EV71 viral load in children with HFMD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-14005153.

Polydatin Induces Apoptosis and Inhibits Growth of Acute Monocytic Leukemia Cells.

Polydatin (PD), a component isolated from Polygonum cuspidatum, has various activities such as inhibiting platelet aggregation, lowering level of blood lipid, reducing lipid peroxidation, and so on. However, the antitumor activity of PD has been poorly reported. In the present study, effect of PD on cell proliferation was evaluated by Cell Counting Kit-8, and cell cycle and apoptosis were investigated by flow cytometry. Meanwhile, the protein expression level of Bc1-2, Bax, cyclin A, cyclin B, and cyclin D1, which associated with apoptosis and cell cycle were analyzed by Western blotting. Results show that PD could effectively inhibit the growth, arrest cells in S phase, and induce apoptosis of acute monocytic leukemia cell line THP-1; meanwhile, expression of cyclin D1 and Bc1-2 decreased significantly, and expression of Bax and cyclin A increased notably. All results suggest that PD maybe a potential therapeutic strategy for acute monocytic leukemia.

[Roles of follicular helper T cells and follicular regulatory T cells in pathogenesis of Henoch-Schönlein purpura in children].

OBJECTIVE: To study the roles of follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells in the pathogenesis of Henoch-Schönlein purpura (HSP) in children. METHODS: Peripheral blood samples were collected from 40 HSP children and 25 healthy controls. The percentages of Tfh and Tfr cells were measured by flow cytometry; the mRNA expression levels of Bcl-6, c-MAF, Blimp-1, and PD-1 in peripheral blood were measured by real-time polymerase chain reaction. RESULTS: Compared with the controls, the children with HSP had significantly increased percentage of Tfh cells and Tfh/Tfr ratio but a significantly reduced percentage of Tfr cells in the peripheral blood (P<0.05). Compared with the controls, the children with HSP had significantly increased mRNA expression of Bcl-6 and c-MAF but significantly reduced mRNA expression of Blimp-1 in CD4+ T cells (P<0.05), and had significantly increased mRNA expression of PD-1 but significantly reduced mRNA expression of Blimp-1 in CD4+CD25+ regulatory T cells (P<0.05). CONCLUSIONS: Abnormal percentages of Tfh and Tfr cells may be involved in the pathogenesis of HSP in children, and over-expression of Bcl-6, c-MAF, and PD-1 mRNA and inhibited expression of Blimp-1 mRNA may be considered as important reasons for abnormal percentages of Tfh and Tfr cells.

[Expression of CD58 in childhood B-lineage acute lymphoblastic leukemia and its feasibility in minimal residual disease detection].

OBJECTIVE: To measure the expression of lymphocyte function-associated antigen-3 (CD58) in childhood B-lineage acute lymphoblastic leukemia (B-ALL) and to explore the feasibility of CD58 as an indicator for minimal residual disease (MRD) detection in childhood B-ALL. METHODS: Eighty-seven children diagnosed with B-ALL between January 2014 and September 2014 were enrolled, and 20 hospitalized children who had no tumor or blood disease and had normal bone marrow cell morphology served as the control group. The expression features of CD58 in bone marrow samples from the two groups (at diagnosis, on day 15 of induction chemotherapy) were analyzed by four-color flow cytometry (FCM). Quantitative real-time polymerase chain reaction (qRT-PCR) and FCM were used to detect MRD in B-ALL patients on day 33 of induction chemotherapy. RESULTS: The mean fluorescence intensity of CD58 expression in the 87 B-ALL cases (91±33) was significantly higher than that in the 20 controls (14±6) (P<0.01); CD58 was over-expressed in 44 of the B-ALL cases. In the B-ALL children, the expression of CD58 on day 15 of induction chemotherapy (105±22) was not significantly different from that at diagnosis (107±26) (P>0.05). In the 44 B-ALL patients with CD58 over-expression, FCM showed 9 MRD(+) cases and 35 MRD(-) cases, while qRT-PCR showed 11 MRD(+) cases and 33 MRD(-) cases; 42 cases (95%) showed consistent results of the two tests, so there was no significant difference between the two methods in detecting MRD (P>0.05). CONCLUSIONS: CD58 is over-expressed and stable in children with B-ALL, and it can be considered as an indicator for MRD detection in childhood B-ALL.

Autocrine motility factor receptor promotes the proliferation of human acute monocytic leukemia THP-1 cells.

The aberrant activation of autocrine motility factor receptor (AMFR) has been implicated in several types of human cancer. The present study aimed to elucidate the effect of AMFR on the regulation of proliferation in an acute monocytic leukemia cell line, THP­1. THP­1 cells were transfected with AMFR­targeted small interfering (si)RNA and a plasmid encoding a truncated AMFR, AMFR­C, (pcDNA3.1­AMFR­C). The mRNA and protein levels of AMFR and the downstream targets, rho­associated, coiled­coil containing protein kinase 2 (ROCK2), cyclin D1, and B­cell lymphoma (Bcl)­2, were measured using reverse transcription­quantitatibe polymerase chain reaction and immunoblot analyses. The effects on cell cycle and apoptosis were investigated using flow cytometry. The present study successfully established the knockdown of AMFR and expression of AMFR­C in the THP­1 cells. Downregulation of AMFR induced cell cycle arrest at the G0/G1 phase, and increased apoptosis of the THP­1 cells (all P<0.05). The AMFR siRNA increased the percentage of early apoptotic cells between 3.88±1.43 and 19.58±4.29% (P<0.05). The expression levels of ROCK2, cyclin D1 and Bcl­2 were reduced by the downregulation of AMFR and enhanced by overexpression of AMFR­C. In conclusion, AMFR appears to be crucial for the proliferation of the THP­1 acute monocytic leukemia cell line. Therefore, AMFR may represent a potential target for the treatment of acute monocytic leukemia.