A postoperative tumor-specific death prediction model for patients with endometrial cancer: a retrospective study.

Background: Endometrial cancer (EC) is an epithelial malignancy occurring in the endometrium, with a 5-year mortality rate of above 10%. However, there is currently a lack of studies exploring the potential of a predictive model of tumor-specific death after surgery in these patients. Methods: From January 2015 to December 2017, data related to 482 patients with EC admitted to the Dushu Lake Hospital Affiliated to Soochow University were analyzed. Patients were divided into death (n=62) and survival (n=420) groups according to whether tumor-specific death occurred at 5 years postoperatively or not. The clinical characteristics of the two groups were compared, and the risk factors for tumor-specific death in patients with EC 5 years after surgery were investigated by logistics regression analysis. A nomogram prediction model was established according to the relevant risk factors. Results: Tumor size, Ki-67 positive rate, Federation International of Gynecology and Obstetrics (FIGO) stage, and the rate of vascular tumor thrombus between the two groups (P<0.05) were found to be the statistically significant factors. Positive Ki-67, tumor size >3.35 cm, stage III, and vascular tumor thrombus were factors that influenced the tumor-specific death at 5 years after surgery (P<0.05). The predictive model obtained an area under the receiver operating characteristic (ROC) curves in the training and verification sets of 0.847 [95% confidence interval (CI): 0.779-0.916] and 0.886 (95% CI: 0.803-0.969), respectively. Conclusions: The nomogram prediction model, which was established in this study, was proved to be valuable in predicting tumor-specific death 5 years after the surgery in patients with EC.

Cancer Cell Membrane-Enveloped Dexamethasone Normalizes the Tumor Microenvironment and Enhances Gynecologic Cancer Chemotherapy.

The aberrant tumor microenvironment (TME), especially immature and leaky vessels, prevents the penetration and accumulation of chemotherapeutics and results in the failure of chemotherapy to treat gynecologic cancer. Herein, dexamethasone (Dex), a glucocorticoid steroid used to moderate tumor extracellular matrix and normalize vessels, was enclosed within a biocompatible material known as poly(lactic-co-glycolic acid) (PLGA), and the obtained Dex@PLGA was further coated with a mouse cervical cancer cell membrane (CM). The formulated Dex@PLGA-CM nanoparticles showed efficient extravascular diffusion within the tumor owing to the homologous targeting abilities inherited from the source cancer cells. The Dex@PLGA-CM nanoparticles greatly reshaped the TME, enhancing the penetration of Doxil and thus markedly improving the therapeutic effect of this drug against cervical cancers. Excitingly, the Dex@PLGA-CM nanoparticles coated with mouse ovarian cancer cell membranes also promoted Doxil-mediated chemotherapy effects in metastatic ovarian cancer when administered intraperitoneally. This work presents an effective nanomedicine for the efficient modification of the TME to enhance the effects of gynecologic cancer chemotherapy.

Long Non-Coding RNA ZEB2-AS1 Augments Activity of Trophoblast Cells and Prevents the Development of Recurrent Spontaneous Abortion in Mice Through EZH2-Mediated CST3 Inhibition.

Recurrent spontaneous abortion (RSA) is the most common complication of pregnancy where reduced invasion of trophoblasts plays a major role. This work aimed to explore the effect of abnormally expressed long non-coding RNA (lncRNA) ZEB2-AS1 on the occurrence of RSA. Differentially expressed lncRNAs in trophoblast cells between healthy controls and patients with RSA were screened using the GEO database. Female CBA/J mice were allowed to mate with male DBA/2 mice to establish inbred mice with RSA. ZEB2-AS1 was poorly expressed in placental tissues and trophoblast cells in the condition of RSA. ZEB2-AS1 upregulation augmented proliferation, migration, and invasion of trophoblast cells in vitro. ZEB2-AS1 negatively regulated cystatin C (CST3) expression. Further overexpression of CST3 blocked the activity of trophoblast cells. ZEB2-AS1 recruited enhancer of EZH2 to the promoter region of CST3, which increased H3K27me3 modification to suppress CST3 expression. In vivo, overexpression of ZEB2-AS1 reduced embryo resorption rate and increased the weights of fetuses and placentas in mice with RSA. However, the protective roles of ZEB2-AS1 were blocked upon artificial silencing of EZH2 or upregulation of CST3. Taken together, this study demonstrates that ZEB2-AS1 enhances activity of trophoblast cells and prevents RSA development through reducing CST3 expression in an EZH2-dependent manner.

The expression level and prognostic value of microRNA-15a-5p in endometrial carcinoma.

BACKGROUND: Recent studies have shown that the microRNA-15a-5p (miR-15a-5p) plays varying roles in different malignancies. However, to date, the role and prognostic value of miR-15a-5p in patients with endometrial cancer has not been explored. This study investigated the expression level of miR-15a-5p in endometrial carcinoma and its prognostic value. METHODS: A total of 108 patients with endometrial cancer treated in our hospital from January 2015 to January 2016 were enrolled in this study. The patients were followed up for 5 years. Patients who experienced recurrence or metastasis after surgery were assigned into the recurrence and metastasis group (n=45) and the remaining patients were assigned into the control group (n=63). The expression level of microRNA-15a-5p in endometrial cancer was analyzed. Furthermore, the correlation between the expression of miR-15a-5p and the pathological features and prognosis was examined. RESULTS: The expression of miR-15a-5p in endometrial carcinoma was significantly lower than that in adjacent healthy tissues (2.22±0.75 vs. 2.59±0.91, P=0.000). Furthermore, the expression of miR-15a-5p in the endometrial cancer tissues of patients in the recurrence and metastasis group was significantly lower than that observed in patients in the control group (1.91±0.62 vs. 2.45±0.75, P=0.000). The receiver operating characteristic curve was used to analyze the predictive value of miR-15a-5p in endometrial cancer tissue for postoperative recurrence or metastasis in endometrial cancer patients. The area under the curve was 0.690 [95% confidence interval (CI): 0.601 to 0.798, P=0.000], the best cut-off value of diagnosis was 2.325, the sensitivity was 0.619, and the specificity was 0.733. Multivariate logistic regression analysis showed that miR-15a-5p expression <2.325 was a risk factor for postoperative recurrence or metastasis of endometrial cancer [odds ratio (OR) =3.544 (95% CI: 1.489 to 8.436), P=0.004]. Furthermore, the expression of miR-15a-5p in endometrial carcinoma was correlated with lymph node metastasis, TNM stage, and patient mortality. CONCLUSIONS: The expression of miR-15a-5p in endometrial carcinoma is related to lymph node metastasis, TNM stage, and mortality. Furthermore, the expression of miR-15a-5p was significantly decreased in endometrial cancer patients with recurrence or metastasis and thus, miR-15a-5p may have certain value in predicting postoperative recurrence or metastasis in such patients.

Progesterone receptor inhibits the proliferation and invasion of endometrial cancer cells by up regulating Krüppel-like factor 9.

BACKGROUND: Krüppel-like factor 9 (KLF9) is one of the most important members of the KLF family, and is abnormally expressed in many tumors. However, the detailed function of KLF9 in endometrial cancer (EC) was barely investigated. METHODS: In this study, a total of 52 paired EC tissues were recruited to detect the KLF9 expression. Then a serial of phenotypic experiments and mechanism researches were performed. RESULTS: The results showed that KLF9 expression was decreased in EC tissues, and the reduced expression of KLF9 is associated with highly metastatic capacity of EC cells. KLF9 could inhibit the proliferation and invasion of EC cells by inhibiting the Wnt/ß-catenin signaling pathway. Progesterone receptor (PR) could bind to KLF9 promoter and a positive correlation between KLF9 and PR expression was witnessed. CONCLUSIONS: Taken together, the reduction of KLF9 induced by PR might participate in the development of EC and targeting KLF9 may provide a novel strategy for EC management.

CD33+ CD14+ CD11b+ HLA-DR- monocytic myeloid-derived suppressor cells recruited and activated by CCR9/CCL25 are crucial for the pathogenic progression of endometriosis.

PROBLEM: Endometriosis (EM) is a chronic immunoinflammatory disease associated with an abnormal immunotolerant microenvironment. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that play a major role in immunosuppression in cancer, inflammation and other diseases. This paper aims to elucidate whether or not MDSCs are involved in regulating this microenvironment in EM and how this regulation occurs. METHOD OF STUDY: Immunochemistry (IHC) and qPCR were conducted to measure CD11b and ARG1 expression in the ectopic endometrium samples from EM patients. CCL25 levels in EM PF and the expression of CCR9 on M-MDSCs were measured by ELISA. M-MDSC migration was determined towards rhCCL25, α-CCR9, α-CCL25 and EM PF through in vitro chemotaxis assay. CD33+ CD14+ CD11b+ HLA-DR- M-MDSCs isolated from EM PBMCs were added to CD8+ T cells stimulated with α-CD3/α-CD28 antibody. After 72 hours of co-culture, proliferation was measured to rate the immunosuppressive function of M-MDSCs. Finally, levels of IL-10, GM-CSF and arginase activity in the cultured supernatants were detected. RESULTS: IHC and qPCR results revealed higher CD11b and ARG1 expression in EM endometrium than normal endometrium. MDSCs accumulated in the EM microenvironment, in which M-MDSCs were the predominant type. CD33+ CD14+ CD11b+ HLA-DR- M-MDSCs expressed high CCR9 levels and were recruited through CCL25. M-MDSCs from EM PBMCs inhibited proliferation and activity in autologous T cells. rhCCL25 promoted IL-10 and GM-CSF secretion and arginase enzymatic activity in CD33+ CD14+ CD11b+ HLA-DR- M-MDSCs. CONCLUSION: CD33+ CD14+ CD11b+ HLA-DR- M-MDSCs recruited and activated by CCR9/CCL25 play a crucial role in the pathogenic progression of endometriosis, thus providing a potential target for EM treatment.

Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth.

In order to improve the sensitivity of cervical cancer cells to irradiation therapy, we targeted hexokinase 2 (HK2), the first rate-limiting enzyme of glycolysis, and explore its role in cervical cancer cells. We suppressed HK2 expression and/or function by shRNA and/or metformin and found HK2 inhibition enhanced cells apoptosis with accelerating expression of cleaved PARP and caspase-3. HK2 inhibition also induced much inferior proliferation of cervical cancer cells both in vitro and in vivo with diminishing expression of mTOR, MIB and MGMT. Moreover, HK2 inhibition altered the metabolic profile of cervical cancer cells to one less dependent on glycolysis with a reinforcement of mitochondrial function and an ablation of lactification ability. Importantly, cervical cancer cells contained HK2 inhibition displayed more sensitivity to irradiation. Further results indicated that HPV16 E7 oncoprotein altered the glucose homeostasis of cervical cancer cells into glycolysis by coordinately promoting HK2 expression and its downregulation of glycolysis. Taken together, our findings supported a mechanism whereby targeting HK2 inhibition contributed to suppress HPV16 E7-induced tumor glycolysis metabolism phenotype, inhibiting tumor growth, and induced apoptosis, blocking the cancer cell energy sources and ultimately enhanced the sensitivity of HPV(+) cervical cancer cells to irradiation therapy.

Dicer1 dysfunction promotes stemness and aggression in endometrial carcinoma.

Endometrial carcinoma is one of the most common gynecological malignancies, but the molecular events involved in the development and progression of endometrial carcinoma remain unclear. Dicer1 and cancer stem cells play important roles in cell motility and survival. This study investigated the role of the let-7 family and Dicer1 in the stemness of endometrial carcinoma cells. We profiled Dicer1 expression in clinical samples and explored its relationship with stem cell-associated markers and clinical parameters. We showed that Dicer1 dysfunction leads to the enrichment of tumor stemness features and tumor aggression both in vitro and in vivo. We also identified the mechanism related to this potential tumor-predisposing phenotype: loss of Dicer1 induced abnormal expression of the let-7 family, which comprises well-known tumor suppressors, thus regulating stemness in endometrial carcinoma cells.

ROR1 promotes the proliferation of endometrial cancer cells.

Endometrial cancer (EC) is the most common gynecological malignant tumor. The canonical Wnt/ß-catenin signaling pathway plays a key role in regulating carcinogenesis, and the noncanonical Wnt5a-ROR1 pathway is an important regulator of Wnt signaling. However, the molecular mechanism by which ROR1 influences Wnt signaling in EC is not known. In this study, we found that ROR1 is expressed at higher levels in tumor tissues and blood samples from patients with stage II EC compared with patients with stage I disease. In vitro, human EC cell lines stably overexpressing ROR1 proliferated more rapidly and formed larger colonies than control cells. Consistent with this, overexpression or knockdown of ROR1 increased or decreased, respectively, the percentage of EC cells in M phase of the cell cycle. Elevated levels of ROR1 were associated with increased expression of Wnt5a and of cyclin D1 and c-Myc, two components of the Wnt signaling pathway. Finally, nude mice grew significantly larger tumors after subcutaneous injection of ROR1-overexpressing EC cells compared with control cells. These findings indicate a novel role for ROR1 in promoting EC cell proliferation by upregulating Wnt5a and stimulating the Wnt/ß-catenin signaling pathway.

Prostaglandin E2 (PGE2) promotes proliferation and invasion by enhancing SUMO-1 activity via EP4 receptor in endometrial cancer.

Prostaglandin E2 (PGE2), a derivative of arachidonic acid, has been identified as a tumorigenic factor in many cancers in recent studies. Prostaglandin E synthase 2 (PTGES2) is an enzyme that in humans is encoded by the PTGES2 gene located on chromosome 9, and it synthesizes PGE2 in human cells. In our study, we selected 119 samples from endometrial cancer patients, with 50 normal endometrium tissue samples as controls, in which we examined the expression of PTGES2. Both immunohistochemistry (IHC) and Western blot analyses demonstrated that synthase PTGES2, which is required for PGE2 synthesis, was highly expressed in endometrium cancer tissues compared with normal endometrium. Stable PTGES2-shRNA transfectants were generated in Ishikawa and Hec-1B endometrial cancer cell lines, and transfection efficiencies were confirmed by RT-PCR and Western blot analyses. We found that PGE2 promoted proliferation and invasion of cells in Ishikawa and Hec-1B cells by cell counting kit-8 tests (CCK8) and transwell assays, respectively. PGE2 stimulation enhanced the expression of SUMO-1, via PGE2 receptor subtype 4 (EP4). Further analysis implicated the Wnt/ß-catenin signaling pathway function as the major mediator of EP4 and SUMO-1. The increase in SUMO-1 activity prompted the SUMOlyation of target proteins which may be involved in proliferation and invasion. These findings suggest SUMO-1 and EP4 as two potential targets for new therapeutic or prevention strategies for endometrial cancers.

SOX17 increases the cisplatin sensitivity of an endometrial cancer cell line.

BACKGROUND: Endometrial cancer (EC) is the most common form of malignant gynecological tumor. Treatment with cisplatin (CDDP) is the mainstay of EC chemotherapy. The apoptotic machinery is regarded as an important etiological factor in chemoresistance. Recent evidence has suggested that overexpression of the transcription factor SOX17 prevented apoptosis in tumor cell lines. The effect of SOX17 on apoptosis in EC cisplatin chemoresistance remains unclear. METHODS: Immunohistochemistry and the reverse transcription-polymerase chain reaction were employed to detect gene expression in paraffin-embedded EC tissues and blood samples. The anti-proliferative ability of SOX17 on EC cells was assessed by MTT. Flow cytometric analysis was used to detect cell apoptosis by annexin V/PI double-staining. The expression of apoptosis-related proteins was analyzed by western blot. In the in vivo study, nude mice were subcutaneously injected with EC cells, and received cisplatin treatment through intraperitoneal chemotherapy. Apoptosis of in vivo samples was analyzed by TUNEL assay. RESULTS: SOX17 expression decreased the chemical resistance of EC cells to CDDP. HEC-1B cells with an elevated expression of SOX17 had a lower cell viability and higher apoptosis rate after cisplatin exposure. Overexpression SOX17 up-regulated wild type p53 after being exposed to cisplatin, while the expression of BCL2-associated X protein and cleaved caspase-3 simultaneously increased. Caspase-9 inhibitor reduced the efficacy of SOX17 in HEC-1B cells after cisplatin treatment. In the in vivo study, SOX17 overexpression clearly restrained the tumor growth and increased the cisplatin toxicity and apoptosis of tumor cells. CONCLUSIONS: SOX17 is involved in the p53-mediated apoptosis pathway, and increases the sensitivity of HEC-1B cells to cisplatin.

Tumor-associated macrophage-derived CXCL8 could induce ERα suppression via HOXB13 in endometrial cancer.

PURPOSE: To elucidate the role of tumor-associated macrophage (TAM) in the loss of ERα in endometrial cancer (EC) and the underlying mechanism. MATERIALS AND METHODS: Tissue microarrays and immunohistochemistry assays were performed using endometrial cancer tissue along with coculture, immunofluorescence, invasion assays and ChIP-qPCR using a human endometrial cancer cell line. RESULTS: Compared with normal tissue, an increased number of TAM was found in EC tissue (34.0 ± 2.6 vs. 8.3 ± 1.1, respectively; p < 0.001), which may downregulate ERα (27.4%, p < 0.05 for HEC-1A and 16.9%, p < 0.05 for Ishikawa) and promote EC cell invasion (1.8-fold, p < 0.001 for HEC-1A and 2.0-fold, p < 0.001 for Ishikawa). Furthermore, we found that TAM-derived CXCL8 mediated the loss of ERα and cancer invasion via HOXB13. HOXB13 was highly expressed in the ERα-negative subtype (r = -0.204, p = 0.002) and low expression of ESR1 was associated with a poor prognosis for EC patients (log-rank p < 0.05). CONCLUSION: TAM-secreted CXCL8 downregulated the ERα expression of EC cells via HOXB13, which may be associated with cancer invasion, metastasis and poor prognosis.

Mutant p53 induces EZH2 expression and promotes epithelial-mesenchymal transition by disrupting p68-Drosha complex assembly and attenuating miR-26a processing.

The tumor suppressor p53 and the transcriptional repressor Enhancer of Zeste Homolog 2 (EZH2) have both been implicated in the regulation of epithelial-mesenchymal transition (EMT) and tumor metastasis via their impacts on microRNA expression. Here, we report that mutant p53 (mutp53) promotes EMT in endometrial carcinoma (EC) by disrupting p68-Drosha complex assembly. Overexpression of mutp53 has the opposite effect of wild-type p53 (WTp53), repressing miR-26a expression by reducing pri-miR-26a-1 processing in p53-null EC cells. Re-expression of miR-26a in mutp53 EC cells decreases cell invasion and promotes mesenchymal-epithelial transition (MET). Rescuing miR-26a expression also inhibits EZH2, N-cadherin, Vimentin, and Snail expression and induces E-cadherin expression both in vitro and in vivo. Moreover, patients with higher serum miR-26a levels have a better survival rate. These results suggest that p53 gain-of-function mutations accelerate EC tumor progression and metastasis by interfering with Drosha and p68 binding and pri-miR-26a-1 processing, resulting in reduced miR-26a expression and EZH2 overexpression.

Autocrine motility factor promotes epithelial-mesenchymal transition in endometrial cancer via MAPK signaling pathway.

Autocrine motility factor (AMF) as a cytokine and a growth factor, is known to regulate tumor cell growth and motility in the progress of various human malignant tumors, however, its role in endometrial cancer (EC) has not been fully studied. In the present study, using immunohistochemistry, we found that AMF was highly expressed in EC tissues compared with normal endometrial tissues and tissue micrioarray technology showed positive correlation between AMF expression and epithelial-to-mesenchymal transition (EMT) related markers E-cadherin, vimentin and Snail. Next, we detected that silencing of AMF by stable transfection with shRNA induced mesenchymal-to-epithelial transition phenotype in Ishikawa and HEC-1B cells by qRT-PCR, western blotting and immunofluorescence. Gene expression profile revealed that AMF silencing resulted in altered expression of EMT related molecular mediators including Snail and transforming growth factor ß receptor 1, and involvement of mitogen-activated protein kinase (MAPK) signaling pathway. Additionally, we found that EMT related markers were downregulated with pretreatment of the MAPK-specific inhibitor U0126 by western blotting. The present study is the first to support a role for AMF mediating EMT in endometrial cancer through MAPK signaling. Therefore, AMF may provide a potential prognostic and therapeutic target in preventing EC progression.

Piwil1 causes epigenetic alteration of PTEN gene via upregulation of DNA methyltransferase in type I endometrial cancer.

Piwil1, a member of the Piwi family, has been well demonstrated to mediate tumorigenesis associated with DNA hypermethylation. It has been reported that Piwil1 is overexpressed in various types of cancer, including endometrial cancer. However, the underlying mechanism of Piwil1 in endometrial cancer remains largely unclear. PTEN exerts an important tumor suppressor role in endometrial carcinogenesis. The present study aimed to investigate whether Piwil1 could regulate the expression of PTEN. Herein, we found that Piwil1 could promote the loss of PTEN expression and increase aberrant hypermethylation of PTEN gene promoter in Ishikawa cells. We also found that Piwil1 could regulate the expression of DNA methyltransferase 1 (DNMT1). Silencing DNMT1 gene could upregulate the PTEN gene expression and change the methylation status of PTEN gene promoter in Ishikawa cells. These results suggested that Piwil1 caused the loss of PTEN expression through DNMT1-mediated PTEN hypermethylation. Taken together, these data provide a novel regulatory mechanism of Piwil1 in endometrial cancer.

Mutant p53 (p53-R248Q) functions as an oncogene in promoting endometrial cancer by up-regulating REGγ.

P53 mutation plays a pivotal role in tumorigenesis of endometrial cancer (EC), here we report that the gain-of-function mutant p53-R248Q targets the proteasome activator REGγ to promote EC progression. Increased p53 expression significantly correlated with high pathological grade and lymph node metastasis in EC specimens. Manipulation of p53-R248Q in EC cells caused coincident changes in REGγ expression, and chromatin immunoprecipitation coupled with PCR further indicated that p53-R248Q bound to the REGγ gene promoter at a p53 responsive element. Silencing of REGγ in EC cells attenuated the cell proliferation, migration and invasion abilities, whereas overexpression of p53-R248Q rescued these activities. Overexpression of REGγ also induced an epithelial-mesenchymal transition phenotype. Moreover, a mouse xenograft tumor model showed that REGγ promoted tumor growth, further demonstrating a p53-R248Q-REGγ oncogenic pathway. Finally, examination of EC and normal endometrium specimens confirmed the oncogenic role of REGγ, in that REGγ was more highly overexpressed in p53-positive specimens than in p53-negative specimens. Our data suggest that REGγ is a promising therapeutic target for EC with the p53-R248Q mutation.

MiR-125b promotes proliferation and migration of type II endometrial carcinoma cells through targeting TP53INP1 tumor suppressor in vitro and in vivo.

BACKGROUND: Our previous studies have identified that miR-125b was overexpressed in type II endometrial carcinoma (EC) cells compared with type I using microRNAs microarray. Although recent studies have shown the important role of miR-125b in several tumors and overexpression of miR-125b in advanced EC, its function in this disease has not yet been defined. In the present study, we tried to confirm the result of microRNAs microarray and further investigated the functions of miR-125b in EC, and tried to find new downstream targets of miR-125b. METHODS: Differential expression of miR-125b was detected between type II EC cells (KLE, AN3CA) with ER negative and type I EC cells (ishikawa, RL95-2) with ER positive by qRT-PCR and northern blotting. The effects of miR-125b of on proliferation, migration, and target protein expression were evaluated by CCK8 assay, wound healing assay, transwell migration assay, western blotting, and Tumorigenicity assays in nude mice. In addition, luciferase reporter plasmid was constructed to demonstrate the direct target of miR-125b. RESULTS: MiR-125b was overexpressed in type II EC cells compared with type I. Exogenous miR-125b expression increased proliferation and migration of ishikawa cells and abrogating expression of miR-125b suppressed proliferation, and migration of AN3CA cells in vitro. In addition, in vivo tumor formation assay confirmed that forced miR-125b expression promoted proliferation potential of ishikawa cells, and tumor suppressor gene Tumor Protein 53-Induced Nuclear Protein 1 (TP53INP1) was identified to be the direct target of miR-125b. CONCLUSIONS: TP53INP1 was newly identified to be the direct downstream target of miR-125b. MiR-125b, which was overexpressed in type II EC cells compared with type I, contributes to malignancy of type II EC possibly through down-regulating TP53INP1.

microRNA-155 regulates angiotensin II type 1 receptor expression in umbilical vein endothelial cells from severely pre-eclamptic pregnant women.

Angiotensin II is critical in pre-eclampsia pathogenesis. In addition, microRNA-155 regulates angiotensin II type 1 receptor expression. We have explored the function of microRNA-155 in pre-eclamptic pregnant women. Human umbilical vein endothelial cells were isolated and cultured from healthy puerperant women and pre-eclampsia patients. The cells were transfected with a mature microRNA-155 plasmid. The effect of microRNA-155 was assessed by Northern blotting, in situ hybridization, quantitative real-time PCR, immunofluorescent staining and Western blotting. In addition, activation of extracellular signal-regulated kinase 1/2 was assessed by co-immunoprecipitation and Western blotting. Severely pre-eclamptic pregnant women expressed less mature miR-155 compared to healthy pregnant women. In addition, angiotensin II type 1 receptor expression decreased substantially in healthy cells and miR-155-transfected cells compared to miR-155-mutant-transfected cells and cells from pre-eclamptic patients. Mature miR-155 reduced angiotensin II-induced extracellular signal-regulated kinase 1/2 activation. In conclusion, endogenous mature miR-155 expression may be an important contributor to the pathogenesis of severe pre-eclampsia.