Clonal evolution from B-cell acute lymphoblastic leukemia with BCR::ABL1 multilineage involvement to acute myeloid leukemia after multiple anti-CD19 chimeric antigen receptor T-cell therapy.

Not available.

Preemptive inotuzumab ozogamicin eradicated measurable residual disease in Ph-negative acute lymphoblastic leukemia relapsed post CD19 CART therapy.

There are no reports of application of inotuzumab ozogamicin (InO) for the treatment of MRD in r/r B-ALL. We firstly report the efficacy of InO for a patient experienced morphological relapse after HSCT and molecular relapse after CART therapy.

Sphingosine kinase 1 contributes to the metastatic potential of epithelial ovarian cancer to the adipocyte-rich niche.

Unlike many solid tumors, epithelial ovarian cancer (EOC) has a clear metastatic predilection to the adipocyte-rich niche, especially the omentum. However, the underlying mechanism driving this process remains incomplete. Here we show that SphK1 is over-expressed in omental metastases compared with ovarian primary tumors in EOC patients. In vitro, inhibition of SphK1 suppressed the metastatic ability of EOC induced by adipocytes. In vivo, blockage of SphK1 could attenuate the omental metastasis of EOC. Importantly, SphK1 modulates adipocyte-induced E/N-cadherin switch through Twist1, a key process in EOC metastasis. Our study reveals a previously unrecognized role of SphK1 in modulating the metastatic tropism of EOC to the adipocyte-rich niche, suggesting a new target for EOC therapy.

Activation of SphK2 contributes to adipocyte-induced EOC cell proliferation.

Epithelial ovarian cancer (EOC) is the leading cause of deaths due to cancer in women. Adipocytes have been suggested to play a key role in the stimulation of EOC growth. However, the mechanisms underlying the adipocyte-induced EOC proliferation remain undefined. Here, we provide the first evidence that adipocytes induce the activation of sphingosine kinase (SphK) 2 in EOC, which represents a novel pathway that mediates the adipocyte-induced EOC growth. SphK2 inhibition in EOC cells led to a remarkable inhibition of the adipocyte-induced cell proliferation. Moreover, the adipocyte-induced SphK2 activation in EOC cells was extracellular signal-regulated protein kinases (ERK) dependent. Furthermore, silencing SphK2 in EOC significantly inhibited the adipocyte-induced expression of phospho-ERK and c-Myc, two crucial players in EOC growth. Collectively, the current study unraveled a previously unrecognized role of SphK2 in the adipocyte-induced growth-promoting action in EOC, suggesting a novel target for EOC treatment.

Inhibition of sphingosine kinase 2 down-regulates ERK/c-Myc pathway and reduces cell proliferation in human epithelial ovarian cancer.

BACKGROUND: Epithelial ovarian cancer (EOC) is the leading cause of death from female cancers. In our previous study, sphingosine kinase 2 (SphK2) inhibitor was shown to display anti-EOC activities. The purpose of this study was to evaluate further the expression characteristics and clinical significance of SphK2 in EOC and to explore the roles and underlying mechanisms of SphK2 in EOC cell survival. METHODS: The expression of SphK2 was examined by immunohistochemistry (IHC) and Western blot, and its clinical implications and prognostic significance were analyzed. We performed a cellular proliferation assay, and a mouse xenograft model was established to confirm the roles of SphK2 in vitro and in vivo. Cell cycle analysis, apoptosis assay, and Western blot were performed to examine cell cycle progression and apoptosis rate. Gene set enrichment analysis (GSEA), and Western blot were used to investigate the downstream signaling pathways related to SphK2 function. RESULTS: The expression level of SphK2 was shown to be associated with stage, histological grade, lymph node metastasis, and ascites status. More importantly, a high SphK2 expression level was a prognostic indicator of overall survival (OS) and relapse-free survival (RFS). Moreover, knockdown of SphK2 arrested cell cycle progression and inhibited EOC cell proliferation both in vitro and in vivo. Furthermore, ERK/c-Myc, the key pathway in EOC progression, was important for SphK2-mediated mitogenic action in EOC cells. CONCLUSIONS: Our findings provided the first evidence that SphK2 played a crucial role in EOC proliferation by regulating the ERK/c-Myc pathway. This indicated that SphK2 might serve as a prognostic marker and potential therapeutic target in EOC.

Activation of SphK1 by adipocytes mediates epithelial ovarian cancer cell proliferation.

BACKGROUND: Adipocytes, active facilitators of epithelial ovarian cancer (EOC) growth, have been implicated in the link between obesity and EOC. However, the current understanding of the mechanisms underlying adipocyte-induced EOC cell proliferation remains incomplete. RESULTS: We provide the first evidence showing that sphingosine kinase (SphK) 1 is critical for adipocyte-induced EOC cell proliferation. Adipocytes are capable of activating SphK1, which then leads to extracellular signal-regulated kinase (ERK) phosphorylation. Moreover, adipocyte-induced SphK1 activation is ERK dependent. Furthermore, sphingosine 1-phosphate receptor (S1PR) 1 and S1PR3, key components of the SphK1 signalling pathway, participate in adipocyte-mediated growth-promoting action in EOC cells. CONCLUSIONS: Our study reveals a previously unrecognized role of SphK1 in adipocyte-induced growth-promoting action in EOC, suggesting a new target for EOC therapy.

Increased let-7b-5p is associated with enhanced BAFF-R expression and B cell survival in immune thrombocytopenia.

BACKGROUND: B cells play a key role in the pathogenesis of immune thrombocytopenia (ITP) by producing platelet autoantibodies. Accumulating evidence suggest that microRNA (miRNA) is a critical regulator in B cells. The contribution of miRNA to B cell dysfunction in ITP has not been described. The aim of this study was to examine the expression of miRNA let-7b-5p in B cells of ITP patients and investigate its possible association with B cell function in ITP. METHODS: The CD19+ cells were isolated from peripheral mononuclear cells of ITP patients and healthy controls using immunomagnetic microbeads. B cell survival in vitro was evaluated by cell counting. The level of let-7b-5p was quantified by quantitative PCR. The surface expression of B cell activating factor receptor (BAFF-R) was detected by flow cytometry. The role of let-7b-5p was examined in isolated B cells by transfecting miRNA mimics or inhibitors. RESULTS: The results showed that let-7b-5p in B cells was elevated, and B cell survival was enhanced in ITP patients compared with healthy controls. BAFF and B cell receptor stimulation can induce the expression of let-7b-5p in vitro. Overexpression of let-7b-5p in B cells enhanced the expression of surface BAFF-R and promoted B cell survival. Moreover, let-7b-5p enhanced the phosphorylation of NF-κB2 p100 and upregulated the expression of survival factor Bcl-xL after BAFF induction. CONCLUSION: Let-7b-5p is a pro-survival miRNA in B cells and increased let-7b-5p is associated with enhanced surface BAFF-R in ITP.

Adipocytes: active facilitators in epithelial ovarian cancer progression?

There is growing evidence that adipocytes play important roles in the progression of multiple cancers. Moreover, in obesity, adipocytes alter their original functions and contribute to the metabolic and inflammatory changes of adipose tissue microenvironment, which can further enhance tumor development. At present, the roles of adipocytes in the pathogenesis of epithelial ovarian cancer (EOC) are far from being fully elucidated. Herein, we summarized the recent advances in understanding the roles of adipocytes in EOC progression. Adipocytes, close neighbors of EOC tissue, promote EOC growth, invasion, metastasis and angiogenesis through adipokine secretion, metabolic remodeling and immune microenvironment modulation. Moreover, adipocytes are important therapeutic targets and may work as useful anticancer drug delivery depot for EOC treatment. Furthermore, adipocytes also act as a therapeutic obstacle for their involvement in EOC treatment resistance. Hence, better characterization of the adipocytes in EOC microenvironment and the crosstalk between adipocytes and EOC cells may provide insights into EOC progression and suggest novel therapeutic opportunities.

Follicle-stimulating hormone promotes the proliferation of epithelial ovarian cancer cells by activating sphingosine kinase.

Follicle-stimulating hormone (FSH) is closely related to the pathogenesis and progression of epithelial ovarian cancer (EOC). However, until now, knowledge relating to FSH-driven signalling pathways that lead to the growth of EOC remained incomplete. We sought to explore whether sphingosine kinase (SphK) could mediate FSH-induced ovarian cancer cell proliferation and which pathway might be involved in this process. The expression of phospho-SphK1 and phospho-SphK2 was detected in sections of EOC tissues by Immunohistochemical staining, and clinical significances were analyzed by statistical analysis. EOC cells were treated with FSH or/and SKI-II. CCK8 assays and colony formation assays were used to investigate cell proliferation. Western blot was carried out to detect protein expression in EOC cell line after treated with FSH. Here, for the first time, we provide evidence that high expression levels of phospho-SphK1 and phospho-SphK2 were both prognostic indicators of overall survival (OS) in EOC. Additionally, the expression levels of both phospho-SphK1 and phospho-SphK2 were closely correlated with the expression level of follicle-stimulating hormone receptor (FSHR) in ovarian cancer tissues. FSH stimulated the phosphorylation of both SphK1 and SphK2 and was able to regulate the survival and growth of ovarian cancer cells by activating SphK1 and SphK2 through ERK1/2. Both isoenzymes of SphK were equally responsible for FSH-induced cell proliferation of EOC. Both Erk1/2 and Akt activation play important roles in mediating FSH-induced cell proliferation after phosphorylation of SphK. Moreover, our data demonstrated that S1P receptor 1 (S1PR1) and S1PR3, key components of the SphK signalling system, were involved in FSH-mediated proliferation of EOC. Taken together, the results of the current study revealed that SphK is an essential mediator in FSH-induced proliferation of ovarian cancer cells in EOC, which indicates a new signalling pathway that controls FSH-mediated growth in EOC and suggests a new strategy that pharmaceutically targets both isoenzymes of SphK for the management of ovarian cancer.

GPX2 silencing relieves epithelial-mesenchymal transition, invasion, and metastasis in pancreatic cancer by downregulating Wnt pathway.

Glutathione peroxidase 2 (GPX2) participates in many cancers including pancreatic cancer (PC), and overexpression of GPX2 promotes tumor growth. Herein, we identified the role of GPX2 in epithelial-mesenchymal transformation (EMT), invasion, and metastasis in PC. Bioinformatics prediction was applied to select PC-related genes. The regulatory function of GPX2 in PC was explored by treatment with short hairpin RNA against GPX2 or LiCl (activator of wingless-type MMTV integration site [Wnt] pathway) in PC cells. GPX2 level in PC tissues, the levels of GPX2, ß-catenin, Vimentin, Snail, epithelial-cadherin (E-cadherin), matrix metalloproteinase 2 (MMP2), MMP9, and Wnt2 in cells were determined. Subsequently, cell proliferation, invasion, and metastasis were assayed. Bioinformatics analysis revealed that GPX2 was involved in PC development mediated by the Wnt pathway. GPX2 was highly expressed in PC tissues. GPX2 silencing downregulated levels of ß-catenin, Vimentin, Snail, MMP2, MMP9, and Wnt2 but upregulated levels of E-cadherin. It was confirmed that GPX2 silencing suppressed PC cell proliferation, metastasis, and invasion. Furthermore, the trend of EMT and invasion and metastasis of PC induced by the LiCl-activated Wnt pathway was reversed when the GPX2 was silenced. GPX2 silencing could inhibit the Wnt pathway, subsequently suppress PC development.

Knockdown of long non-coding RNA LINC00176 suppresses ovarian cancer progression by BCL3-mediated down-regulation of ceruloplasmin.

Ovarian cancer is a common malignancy among women with some clinically approved diagnostic coding gene biomarkers. However, long non-coding RNAs (lncRNAs) have been indicated to play an important role in controlling tumorigenesis of ovarian cancer. Hereby, the aim of the study was to uncover the function of lncRNA LINC00176 in the development and progression of ovarian cancer by regulating ceruloplasmin (CP). Bioinformatics prediction in combination with RT-qPCR analysis for the expression pattern of LINC00176 revealed that LINC00176 was highly expressed in ovarian cancer tissues as well as in ovarian cancer cell lines, respectively. LINC00176 was predominantly localized in the nucleus. Delivery of si-LINC00176, oe-LINC00176, si-BCL3 and si-CP plasmids was conducted to explore the effects of LINC00176 on ovarian cancer. Promoted proliferation, migration and invasion along with reduced apoptosis were observed in cells treated with oe-LINC00176, while si-BCL3 and si-CP were able to block the promoting effects. Investigations with regard to the correlation between LINC00176 and promoter region of CP turned out to be positive via B-cell CLL/lymphoma 3 (BCL3) by means of dual-luciferase reporter gene assay, ChIP and RIP assays. Furthermore, oncogenic properties of the LINC00176/BCL3/CP axis were also demonstrated by tumour formation in vivo generated upon injecting cells in nude mice. Our results demonstrate that restored LINC00176 initiates tumorigenesis in ovarian cancer by increasing CP expression via recruiting BCL3, the mechanism of which represented a potential and promising therapeutic target for the disease.

Sphingosine kinase 2 inhibitor ABC294640 displays anti-epithelial ovarian cancer activities in vitro and in vivo.

Background: ABC294640 is a non-lipid competitive inhibitor of SphK2. It exhibited anti-proliferative activities in many human malignancies, including ovarian cancer. However, its potential mechanism of action remains poorly understood. Methods: In this paper, epithelial ovarian cancer (EOC) cell lines SKOV3 and HO8910 were treated with ABC294640. In order to explore the effect of ABC294640 on the behavior of ovarian cancer cells in vitro, we used cell counting kit-8 (CCK-8) assays, colony formation assays, flow cytometry, quantitative real-time PCR (qRT-PCR), Western blot analysis and immunohistochemistry to detect the effect of ABC294640 on cell proliferation, cell cycle distribution, cell apoptosis, the expression of related factors at mRNA levels, and the expression of related factors at protein level. An intra-abdominal xenograft tumor model of EOC was set up to assess the tumor growth in nude mice. Results: The results obtained indicate that EOC cell proliferation was noticeably inhibited in a concentration-dependent manner by ABC294640. ABC294640 caused cell cycle arrest in S phase and increased cell apoptosis rate in EOC cells. Also, the proteins, including phosphorylated retinoblastoma protein (P -Rb), cyclin D1, cyclin B1, and Bcl-2 were significantly inhibited, while cleaved-caspase 3 was activated. ABC294640 inhibited the expression of c-Myc in EOC. The in vivo assay showed an inhibitory effect of ABC294640 on tumor growth. Conclusions: ABC294640 could downregulate the expression of c-Myc in EOC both in vitro and in vivo. ABC294640 inhibited tumor growth in EOC via cell cycle arrest and inducing cell apoptosis both in vitro and in vivo, partially by decreasing the expression of cell cycle-associated proteins (such as P-Rb, cyclin B1, and cyclin D1) and promoting caspase 3 activation via downregulation expression of c-Myc. It suggested that ABC294640 had the potential to serve as an agent in EOC treatment.

Altered circulating T follicular helper cells in patients with chronic immune thrombocytopenia.

The present study aimed to illuminate the role of circulating T follicular helper (TFH) cells in patients diagnosed with chronic immune thrombocytopenia (cITP). Fifty-four patients with cITP and 30 age-matched healthy control subjects were enrolled in the present study. TFH cell frequencies, expression of CD4+ TFH cell-associated cytokines, including interleukin (IL)-2, IL-4, IL-10 and IL-21 and associated regulatory mRNA expression levels including Bcl-6, c-Maf, Blimp-1 and PD-1 pre- and post-treatment with intravenous immunoglobulin and corticosteroids, were detected by flow cytometry, ELISA and reverse transcription-quantitative polymerase chain reaction, respectively. TFH cell frequencies of patients were significantly higher compared with healthy controls pre-treatment (P<0.05). Following treatment, significantly decreased percentages of TFH cells were present in cITP responders (P<0.05). Correlation analysis revealed that the number of TFH cells was negatively correlated with the platelet count in the peripheral blood. Furthermore, analysis of inflammatory cytokines indicated significant differences in serum interleukin (IL)-21 and IL-10 between pretreated patients and healthy controls (P<0.05). Additionally, transcription factor B-cell lymphoma (Bcl)-6, c-Maf and programmed death-ligand (PD)-1 mRNA expression levels were significantly different between cITP patients prior to treatment and the healthy controls (P<0.05). However, the expression levels of Bcl-6, C-Maf and PD-1 mRNA were significantly changed post-treatment (P<0.05). These data demonstrated that circulating TFH cells and CD4+ TFH cell-associated cytokines may serve a role in cITP. The findings suggest that the overactivation of TFH cells may contribute to the immunopathogenesis of cITP, thus blocking the pathway of TFH cells may be reasonable for therapeutic intervention.

Sphingosine kinase 1/sphingosine-1-phosphate (S1P)/S1P receptor axis is involved in ovarian cancer angiogenesis.

Sphingosine kinase (SphK)/sphingosine-1-phosphate (S1P)/S1P receptor (S1PR) signaling pathway has been implicated in a variety of pathological processes of ovarian cancer. However, the function of this axis in ovarian cancer angiogenesis remains incompletely defined. Here we provided the first evidence that SphK1/S1P/S1PR1/3 pathway played key roles in ovarian cancer angiogenesis. The expression level of SphK1, but not SphK2, was closely correlated with the microvascular density (MVD) of ovarian cancer tissue. In vitro, the angiogenic potential and angiogenic factor secretion of ovarian cancer cells could be attenuated by SphK1, but not SphK2, blockage and were restored by the addition of S1P. Moreover, in these cells, we found S1P stimulation induced the angiogenic factor secretion via S1PR1 and S1PR3, but not S1PR2. Furthermore, inhibition of S1PR1/3, but not S1PR2, attenuated the angiogenic potential and angiogenic factor secretion of the cells. in vivo, blockage of SphK or S1PR1/3 could attenuate ovarian cancer angiogenesis and inhibit angiogenic factor expression in mouse models. Collectively, the current study showed a novel role of SphK1/S1P/S1PR1/3 axis within the ovarian cancer, suggesting a new target to block ovarian cancer angiogenesis.

Clinical significance of circulating microparticles in Ph- myeloproliferative neoplasms.

Microparticles (MPs) are small membrane vesicles that are classified into subcategories based on their origin, such as platelet-derived MPs (PMPs), endothelial MPs (EMPs), red blood cell MPs (RMPs) and tissue factor MPs (TF + MPs). Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPN) are disorders characterized by abnormal haematopoiesis, thrombosis and the JAK2V617F mutation. MPs are biomarkers for procoagulant state in cancer patients, but their relevance in patients with Ph-MPN was unclear. The present study aimed to measure MP variation in MPN patients and evaluate association with the JAK2V617F mutation and with thrombosis and splenomegaly. In total, 92 patients with MPN were enrolled in the present study, including 60 with essential thrombocythaemia (ET), 20 with polycythaemia vera (PV), and 12 with primary myelofibrosis (PMF). RMPs, PMPs, TF + MPs and EMPs were measured by flow cytometry. The levels of RMPs, PMPs, EMPs and TF + MPs in patients with Ph-MPN were all found to be significantly increased compared with controls (P<0.05). Additionally, the levels of all four types of MPs in the PMF group were significantly increased compared with the PV group (P<0.05), and the level of RMPs in the PMF group was significantly increased compared with the ET group (P<0.05). MP levels were increased in the Ph-MPN patients with thrombosis compared with patients without thrombosis (P<0.05). MP levels were increased in Ph-MPN patients with splenomegaly compared with patients without splenomegaly (P<0.05). The level of PMPs in patients with the JAK2V617F mutation was increased compared with patients without the mutation (P<0.05). In conclusion, the present study showed that MPs are associated with Ph-MPN pathogenesis, and may promote thrombosis.

[Differentiation of K562 Cells Induced by Pulsatilla Saponin A into Erythroid Lineage].

OBJECTIVE: To explore the differentiation-inducing potentiality of Pulsatilla saponin A on K562 cells. METHODS: Pulsatilla saponin A of different concentrations was used to treat K562 cells; the benzidine staining and the hemoglobinometry were applied to measure the change of hemoglobin content; the flow cytometry (FCM) was used to detect the expression of CD71 and GPA on K562 cells. RESULTS: K562 cells treated with 4 µg/ml pulsatilla saponin A differentiated into the erythroid lineage. With the treatment of pulsatilla saponin A, the hemoglobin content in K562 cells increased significantly; CD71 and GPA expression on the K562 cell surface were up-regulated. CONCLUSION: Pulsatilla saponin A can induce K562 cells to differentiate into erythroid lineage.

Pulsatilla saponin A induces differentiation in acute myeloid leukemia in vitro.

OBJECTIVES: To identify whether Pulsatilla saponin A (PsA), an active molecule extracted from Pulsatilla chinensis regel, can induce acute myeloid leukemia (AML) cells differentiate. METHODS: PsA was isolated from P. chinensis, and its effects of differentiation induction on both AML cell lines and the primary leukemia cells were investigated. RESULTS: Compared with the untreated control, PsA induced the differentiation of U937 cells, K562 cells and HL-60 cells, represented as the increased CD15+ cells in a dose- and time-dependent manner in all the three AML cell lines, after PsA treatment. As the same time, the cell morphology of these AML cells was changed correspondingly; the cytoplasm/nuclei ratio was increased, basophilic cytoplasm was decreased, and eccentric nucleus and granules were also observed. Also, the same effects of differentiation induction by PSA were confirmed in the primary leukemia cells. However, the specific MEK/ERK inhibitor U0126 effectively abrogated the differentiation induced by PsA in vitro. CONCLUSIONS: PsA can modify the differentiation activity of AML cells, probably though the MEK/ERK signaling pathway.

[Alteration of Microparticle Levels in Early Complications During Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To investigate the alteration of microparticles (MP) in the recipients following hematopoietic stem cell transplantation (HSCT) and its significance, and to search the early diagnostic indicators of thrombotic complications after transplantation. METHODS: According to the occurrence of transplantation-associated complications, 94 allo-HSCT patients were divided into 4 groups: thrombotic group (VOD n = 7, TMA n = 2), acute graft-versus-host disease (aGVHD) group (n = 27), infection group (n = 41) and non-complication group (n = 17). Alterations of serum concentration of tissue factor positive microparticles (TF(+) MP) and endothelial microparticles (EMP) were analyzed by flow cytometry during the process of conditioning treatment and the early stage after transplantation. The relation of these 2 kinds of MP with complications was analysed. RESULTS: (1) The levels of TF(+) MP and EMP of patients undogoing allo-HSCT before conditioning treatment were obviously higher than those in normal controls, and showed some elevation during different times, but there was no significant statistical difference. Although the levels of TF(+) MP and EMP at the end of conditioning treatment were some higher than those before conditioning treatment, but there was no statistical difference between them. (2)The levels of TF(+) MP and EMP in thrombotic group were obviously higher than those in aGVHD group and infection group (P < 0.05). (3)The levels of TF(+) MP and EMP in thrombotic group at different times were significant differences from those in other groups (P < 0.05), and the levels of TF(+) MP and EMP were no significant difference from those in non-complication group. CONCLUSION: The increase of the TF(+) MP and EMP levels may be associated with occurrence of thrombosis after transplantation, indicating occurrence of the thrombotic complications, like hepatic vein occulusive disease (HVOD). The dynamically monitoring levels of TF(+) MP and EMP contributes to early discovery of thrombotic complications.

MiR-199a inhibits the angiogenic potential of endometrial stromal cells under hypoxia by targeting HIF-1α/VEGF pathway.

We previously reported that miR-199a suppressed the invasiveness of endometrial stromal cells (ESCs) by targeting IkappaB kinase beta (IKKß). This study was to investigate the role of miR-199a in the angiogenic potential of ESCs under hypoxia. Forced overexpression of miR-199a in ESCs significantly attenuated its angiogenic potential under hypoxia. Moreover, miR-199a down-regulated the expression level of vascular endothelial growth factor-A (VEGF-A) in ESCs under hypoxic conditions. To delineate the mechanism by which miR-199a reduced VEGF-A production, further analysis of the target genes of miR-199a showed that miR-199a targeted both VEGF-A and Hypoxia-inducible factor (HIF)-1α in ESCs. Our findings indicate that miR-199a may attenuate the angiogenic potential of ESCs under hypoxia partly through HIF-1α/VEGF-A pathway suppression. Therefore, miR-199a may play pivotal roles in the pathogenesis of endometriosis and may become a potential therapeutic target of this disease.

MicroRNA-7 inhibits tumor metastasis and reverses epithelial-mesenchymal transition through AKT/ERK1/2 inactivation by targeting EGFR in epithelial ovarian cancer.

Epidermal growth factor receptor (EGFR) overexpression and activation result in increased proliferation and migration of solid tumors including ovarian cancer. In recent years, mounting evidence indicates that EGFR is a direct and functional target of miR-7. In this study, we found that miR-7 expression was significantly downregulated in highly metastatic epithelial ovarian cancer (EOC) cell lines and metastatic tissues, whereas the expression of, EGFR correlated positively with metastasis in both EOC patients and cell lines. Overexpression of miR-7 markedly suppressed the capacities of cell invasion and migration and resulted in morphological changes from a mesenchymal phenotype to an epithelial-like phenotype in EOC. In addition, overexpression of miR-7 upregulated CK-18 and ß-catenin expression and downregulated Vimentin expression, accompanied with EGFR inhibition and AKT/ERK1/2 inactivation. Similar to miR-7 transfection, silencing of EGFR with this siRNA in EOC cells also upregulated CK-18 and ß-catenin expression and downregulated Vimentin expression, and decreased phosphorylation of both Akt and ERK1/2, confirming that EGFR is a target of miR-7 in reversing EMT. The pharmacological inhibition of PI3K-AKT and ERK1/2 both significantly enhanced CK-18 and ß-catenin expression and suppressed vimentin expression, indicating that AKT and ERK1/2 pathways are required for miR-7 mediating EMT. Finally, the expression of miR-7 and EGFR in primary EOC with matched metastasis tissues was explored. It was showed that miR-7 is inversely correlated with EGFR. Taken together, our results suggested that miR-7 inhibited tumor metastasis and reversed EMT through AKT and ERK1/2 pathway inactivation by reducing EGFR expression in EOC cell lines. Thus, miR-7 might be a potential prognostic marker and therapeutic target for ovarian cancer metastasis intervention.