Loss of m6A demethylase ALKBH5 alleviates hypoxia-induced pulmonary arterial hypertension via inhibiting Cyp1a1 mRNA decay.

BACKGROUND: Hypoxia-induced pulmonary artery hypertension (HPH) is a complication of chronic hypoxic lung disease and the third most common type of pulmonary artery hypertension (PAH). Epigenetic mechanisms play essential roles in the pathogenesis of HPH. N6-methyladenosine (m6A) is an important modified RNA nucleotide involved in a variety of biological processes and an important regulator of epigenetic processes. To date, the precise role of m6A and regulatory molecules in HPH remains unclear. METHODS: HPH model and pulmonary artery smooth muscle cells (PASMCs) were constructed from which m6A changes were observed and screened for AlkB homolog 5 (Alkbh5). Alkbh5 knock-in (KI) and knock-out (KO) mice were constructed to observe the effects on m6A and evaluate right ventricular systolic pressure (RVSP), left ventricular and septal weight [RV/(LV + S)], and pulmonary vascular remodeling in the context of HPH. Additionally, the effects of Alkbh5 knockdown using adenovirus were examined in vitro on m6A, specifically in PASMCs with regard to proliferation, migration and cytochrome P450 1A1 (Cyp1a1) mRNA stability. RESULTS: In both HPH mice lung tissues and hypoxic PASMCs, a decrease in m6A was observed, accompanied by a significant up-regulation of Alkbh5 expression. Loss of Alkbh5 attenuated the proliferation and migration of hypoxic PASMCs in vitro, with an associated increase in m6A modification. Furthermore, Alkbh5 KO mice exhibited reduced RVSP, RV/(LV + S), and attenuated vascular remodeling in HPH mice. Mechanistically, loss of Alkbh5 inhibited Cyp1a1 mRNA decay and increased its expression through an m6A-dependent post-transcriptional mechanism, which hindered the proliferation and migration of hypoxic PASMCs. CONCLUSION: The current study highlights the loss of Alkbh5 impedes the proliferation and migration of PASMCs by inhibiting post-transcriptional Cyp1a1 mRNA decay in an m6A-dependent manner.

Targeting deubiquitinase OTUB1 protects vascular smooth muscle cells in atherosclerosis by modulating PDGFRß.

Atherosclerosis is a chronic artery disease that causes various types of cardiovascular dysfunction. Vascular smooth muscle cells (VSMCs), the main components of atherosclerotic plaque, switch from contractile to synthetic phenotypes during atherogenesis. Ubiquitylation is crucial in regulating VSMC phenotypes in atherosclerosis, and it can be reversely regulated by deubiquitinases. However, the specific effects of deubiquitinases on atherosclerosis have not been thoroughly elucidated. In this study, RNAi screening in human aortic smooth muscle cells was performed to explore the effects of OTU family deubiquitinases, which revealed that silencing OTUB1 inhibited PDGF-BB-stimulated VSMC phenotype switch. Further in vivo studies using Apoe-/- mice revealed that knockdown of OTUB1 in VSMCs alleviated atherosclerosis plaque burden in the advanced stage and led to a stable plaque phenotype. Moreover, VSMC proliferation and migration upon PDGF-BB stimulation could be inhibited by silencing OTUB1 in vitro. Unbiased RNA-sequencing data indicated that knocking down OTUB1 influenced VSMC differentiation, adhesion, and proliferation. Mass spectrometry of ubiquitinated protein confirmed that proteins related to cell growth and migration were differentially ubiquitylated. Mechanistically, we found that OTUB1 recognized the K707 residue ubiquitylation of PDGFRß with its catalytic triad, thereby reducing the K48-linked ubiquitylation of PDGFRß. Inhibiting OTUB1 in VSMCs could promote PDGFRß degradation via the ubiquitin-proteasome pathway, so it was beneficial in preventing VSMCs' phenotype switch. These findings revealed that knocking down OTUB1 ameliorated VSMCs' phenotype switch and atherosclerosis progression, indicating that OTUB1 could be a valuable translational therapeutic target in the future.

ANNEXIN A2 FACILITATES NEOVASCULARIZATION TO PROTECT AGAINST MYOCARDIAL INFARCTION INJURY VIA INTERACTING WITH MACROPHAGE YAP AND ENDOTHELIAL INTEGRIN Β3.

ABSTRACT: Cardiac macrophages with different polarization phenotypes regulate ventricular remodeling and neovascularization after myocardial infarction (MI). Annexin A2 (ANXA2) promotes macrophage polarization to the repair phenotype and regulates neovascularization. However, whether ANXA2 plays any role in post-MI remodeling and its underlying mechanism remains obscure. In this study, we observed that expression levels of ANXA2 were dynamically altered in mouse hearts upon MI and peaked on the second day post-MI. Using adeno-associated virus vector-mediated overexpression or silencing of ANXA2 in the heart, we also found that elevation of ANXA2 in the infarcted myocardium significantly improved cardiac function, reduced cardiac fibrosis, and promoted peri-infarct angiogenesis, compared with controls. By contrast, reduction of cardiac ANXA2 exhibited opposite effects. Furthermore, using in vitro coculture system, we found that ANXA2-engineered macrophages promoted cardiac microvascular endothelial cell (CMEC) proliferation, migration, and neovascularization. Mechanistically, we identified that ANXA2 interacted with yes-associated protein (YAP) in macrophages and skewed them toward pro-angiogenic phenotype by inhibiting YAP activity. In addition, ANXA2 directly interacted with integrin ß3 in CMECs and enhanced their growth, migration, and tubule formation. Our results indicate that increased expression of ANXA2 could confer protection against MI-induced injury by promoting neovascularization in the infarcted area, partly through the inhibition of YAP in macrophages and activation of integrin ß3 in endothelial cells. Our study provides new therapeutic strategies for the treatment of MI injury.

Semaphorin3A Exacerbates Cardiac Microvascular Rarefaction in Pressure Overload-Induced Heart Disease.

Microvascular endothelial cells (MiVECs) impair angiogenic potential, leading to microvascular rarefaction, which is a characteristic feature of chronic pressure overload-induced cardiac dysfunction. Semaphorin3A (Sema3A) is a secreted protein upregulated in MiVECs following angiotensin II (Ang II) activation and pressure overload stimuli. However, its role and mechanism in microvascular rarefaction remain elusive. The function and mechanism of action of Sema3A in pressure overload-induced microvascular rarefaction, is explored, through an Ang II-induced animal model of pressure overload. RNA sequencing, immunoblotting analysis, enzyme-linked immunosorbent assay, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and immunofluorescence staining results indicate that Sema3A is predominantly expressed and significantly upregulated in MiVECs under pressure overload. Immunoelectron microscopy and nano-flow cytometry analyses indicate small extracellular vesicles (sEVs), with surface-attached Sema3A, to be a novel tool for efficient release and delivery of Sema3A from the MiVECs to extracellular microenvironment. To investigate pressure overload-mediated cardiac microvascular rarefaction and cardiac fibrosis in vivo, endothelial-specific Sema3A knockdown mice are established. Mechanistically, serum response factor (transcription factor) promotes the production of Sema3A; Sema3A-positive sEVs compete with vascular endothelial growth factor A to bind to neuropilin-1. Therefore, MiVECs lose their ability to respond to angiogenesis. In conclusion, Sema3A is a key pathogenic mediator that impairs the angiogenic potential of MiVECs, which leads to cardiac microvascular rarefaction in pressure overload-induced heart disease.

Hypoxia Induces M2 Macrophages to Express VSIG4 and Mediate Cardiac Fibrosis After Myocardial Infarction.

M2 macrophage-mediated tissue repair plays an important role in acute myocardial infarction (AMI). Additionally, VSIG4, which is mainly expressed on tissue-resident and M2 macrophages, is crucial for the regulation of immune homeostasis; however, its effects on AMI remain unknown. In this study, we aimed to investigate the functional significance of VSIG4 in AMI using VSIG4 knockout and adoptive bone marrow transfer chimeric models. We also determined the function of cardiac fibroblasts (CFs) through gain- or loss-of-function experiments. We showed that VSIG4 promotes scar formation and orchestrates the myocardial inflammatory response after AMI, while also promoting TGF-ß1 and IL-10. Moreover, we revealed that hypoxia promotes VSIG4 expression in cultured bone marrow M2 macrophages, ultimately leading to the conversion of CFs to myofibroblasts. Our results reveal a crucial role for VSIG4 in the process of AMI in mice and provide a potential immunomodulatory therapeutic avenue for fibrosis repair after AMI.

Role of Mydgf in the regulation of hypoxia/reoxygenation-induced apoptosis in cardiac microvascular endothelial cells.

We aimed to explore the effects of myeloid-derived growth factor (Mydgf) on the regulation of hypoxia/reoxygenation (HR)-induced apoptosis of cardiac microvascular endothelial cells (CMECs). CMECs were exposed to hypoxia for 24 h and reoxygenation for 6 h to establish an HR cell model. Subsequently, an adenovirus was used to overexpress Mydgf in CMECs. Flow cytometry and TUNEL staining were used to detect the extent of apoptosis, whereas qPCR was used to detect the relative expression of Mydgf mRNA. Western blotting was also performed to detect the expression of apoptosis-related proteins and endoplasmic reticulum stress (ERS)-related proteins, including C/EBP Homologous Protein (CHOP), glucose-regulated protein 78 (GRP 78), and cleaved Caspase-12. The endoplasmic reticulum stress agonist tunicamycin (TM) was used to stimulate CMECs for 24 h as a rescue experiment for Mydgf. Flow cytometry revealed that the HR model effectively induced endothelial cell apoptosis, whereas qPCR and western blotting showed that Mydgf mRNA and protein levels decreased significantly after HR treatment (P < 0.05). Overexpression of Mydgf in cells effectively reduced apoptosis after HR. Furthermore, western blotting showed that HR induced a significant upregulation of CHOP, GRP78, and cleaved-Caspase-12 expression in CMECs, whereas HR-treated cells downregulated the expression of CHOP, GRP78, and cleaved-Caspase-12 after Mydgf overexpression. Under HR conditions, TM significantly reversed the protective effect of Mydgf on CMECs. Mydgf may reduce CMEC apoptosis induced by HR by regulating oxidative stress in ERS.

Exosomal MiR-29a in Cardiomyocytes Induced by Angiotensin II Regulates Cardiac Microvascular Endothelial Cell Proliferation, Migration and Angiogenesis by Targeting VEGFA.

BACKGROUND: Exosomes released from cardiomyocytes (CMs) potentially play an important role in angiogenesis through microRNA (miR) delivery. Studies have reported an important role for miR-29a in regulating angiogenesis and pathological myocardial hypertrophy. However, whether CMderived exosomal miR-29a is involved in regulating cardiac microvascular endothelial cell (CMEC) homeostasis during myocardial hypertrophy has not been determined. METHODS: Angiotensin II (Ang II) was used to induce CM hypertrophy, and ultracentrifugation was then used to extract exosomes from a CM-conditioned medium. CMECs were cocultured with a conditioned medium in the presence or absence of exosomes derived from CMs (Nor-exos) or exosomes derived from angiotensin II-induced CMs (Ang II-exos). Moreover, a rescue experiment was performed using CMs or CMECs infected with miR-29a mimics or inhibitors. Tube formation assays, Transwell assays, and 5-ethynyl-20-deoxyuridine (EdU) assays were then performed to determine the changes in CMECs treated with exosomes. The miR-29a expression was measured by qRT-PCR, and Western blotting and flow cytometry assays were performed to evaluate the proliferation of CMECs. RESULTS: The results showed that Ang II-induced exosomal miR-29a inhibited the angiogenic ability, migratory function, and proliferation of CMECs. Subsequently, the downstream target gene of miR- 29a, namely, vascular endothelial growth factor (VEGFA), was detected by qRT-PCR and Western blotting, and the results verified that miR-29a targeted the inhibition of the VEGFA expression to subsequently inhibit the angiogenic ability of CMECs. CONCLUSION: Our results suggest that exosomes derived from Ang II-induced CMs are involved in regulating CMCE proliferation, migration, and angiogenesis by targeting VEGFA through the transfer of miR-29a to CMECs.

The Preventive Role of Hydrogen-Rich Water in Thioacetamide-Induced Cholangiofibrosis in Rat Assessed by Automated Histological Classification.

Background: Cholangiofibrosis is a controversial intrahepatic cholangial lesion that precedes the development of cholangiocarcinoma. Here, we demonstrate that molecular hydrogen (H2) can be used to effectively prevent cholangiofibrosis. Methods: The safety and quality of life (QOL) of rats was firstly evaluated. H2 was administered to rats subjected to thioacetamide (TAA)-induced cholangiofibrosis throughout the whole process. Then, rats were administrated with TAA for 3 months and then followed by H2 intervention. Rat livers were harvested and assessed by light microscopy and convolutional neural network. RNA-seq was performed to analyze the genetic changes in these animal models. Results: Continuous use of H2-rich water was safe and improved QOL.The incidence and average number of cholangiofibrosis in the liver were higher in the TAA group (100%, 12.0 ± 10.07) than that in the H2 group (57.1%, 2.86 ± 5.43). The AI algorithm revealed higher Alesion/Aliver in the TAA group (19.6% ± 9.01) than that in the H2 group (7.54% ± 11.0). RNA-seq analysis revealed that H2 results in a decline in glycolysis. Moreover, in the third experiment, the incidence of microscopic or suspicious tumors and the ratio of liver lesions was decreased after long-term use of H2 (12.5%, 0.57% ± 0.45) compared with untreated group (100%, 0.98% ± 0.73). A number of intestinal microbiota was changed after H2 usage, including clostridiaceae_1, ruminococcus, turicibacter, coriobacteriales, actinobacteria, and firmicutes_bacterium. Conclusion: Hydrogen-rich water protects against liver injury and cholangiofibrosis and improved quality of life partially through regulating the composition of intestinal flora.

Loss of m6A demethylase ALKBH5 promotes post-ischemic angiogenesis via post-transcriptional stabilization of WNT5A.

BACKGROUND: Post-ischemic angiogenesis is critical for blood flow recovery and ischemic tissue repair. N6-methyladenosine (m6A) plays essential roles in numerous biological processes. However, the impact and connected mechanism of m6A on post-ischemic angiogenesis are not fully understood. METHODS: AlkB homolog 5 (ALKBH5) was screened out among several methyltransferases and demethylases involved in dynamic m6A regulation. Cardiac microvascular endothelial cells (CMECs) angiogenesis and WNT family member 5A (WNT5A) stability were analyzed upon ALKBH5 overexpression with adenovirus or knockdown with small interfering RNAs in vitro. The blood flow recovery, capillary, and small artery densities were evaluated in adeno-associated virus (AAV)-ALKBH5 overexpression or ALKBH5 knockout (KO) mice in a hind-limb ischemia model. The same experiments were conducted to explore the translational value of transient silencing of ALKBH5 with adenovirus. RESULTS: ALKBH5 was significantly upregulated in hypoxic CMECs and led to a global decrease of m6A level. ALKBH5 overexpression further reduced m6A level in normoxic and hypoxic CMECs, impaired proliferation, migration, and tube formation only in hypoxic CMECs. Conversely, ALKBH5 knockdown preserved m6A levels and promoted angiogenic phenotypes in hypoxic but not in normoxic CMECs. Mechanistically, ALKBH5 regulated WNT5A expression through post-transcriptional mRNA modulation in an m6A-dependent manner, which decreased its stability and subsequently impeded angiogenesis in hypoxic CMECs. Furthermore, ALKBH5 overexpression hindered blood flow recovery and reduced CD31 and alpha-smooth muscle actin expression in hind-limb ischemia mice. As expected, ALKBH5-KO mice exhibited improved blood flow recovery, increased capillary, and small artery densities after hind-limb ischemia, and similar beneficial effects were observed in mice with transient adenoviral ALKBH5 gene silencing. CONCLUSION: We demonstrate that ALKBH5 is a negative regulator of post-ischemic angiogenesis via post-transcriptional modulation and destabilization of WNT5A mRNA in an m6A-dependent manner. Targeting ALKBH5 may be a potential therapeutic option for ischemic diseases, including peripheral artery disease.

CircUbe3a from M2 macrophage-derived small extracellular vesicles mediates myocardial fibrosis after acute myocardial infarction.

Objective: This study aimed to explore the role of circular RNAs (circRNAs) in M2 macrophage (M2M)-derived small extracellular vesicles (SEVs) in myocardial fibrosis development. Methods: The regulatory role of M2M-derived extracellular vesicles (EVs) was evaluated in a mouse model of acute myocardial infarction. Immunofluorescence, quantitative real-time PCR (RT-qPCR), nanoparticle tracking analysis, Western blot analysis and electron microscopy were used to identify macrophages, large extracellular vesicles (LEVs) and SEVs. The circRNA expression profiles of M0 macrophages (M0Ms) and M2Ms were determined by microarray analysis. Bioinformatic analysis, cell coculture and cell proliferation assays were performed to investigate the expression, function, and regulatory mechanisms of circUbe3a in vitro. qPCR, RNA immunoprecipitation (RIP), dual-luciferase reporter assays, RNA fluorescence in situ hybridization (RNA-FISH), Western blot analysis and a series of rescue experiments were used to verify the correlation among circUbe3a, miR-138-5p and RhoC. Results: CircUbe3a from M2M-derived SEVs triggered functional changes in cardiac fibroblasts (CFs). CircUbe3a was synthesized and loaded into SEVs during increased M2M infiltration after myocardial infarction. The fusion of the released SEVs with the plasma membrane likely caused the release of circUbe3a into the cytosol of CFs. Silencing or overexpressing circUbe3a altered CF proliferation, migration, and phenotypic transformation in vitro. We confirmed that circUbe3a plays a crucial role in enhancing functional changes in CFs by sponging miR-138-5p and then translationally repressing RhoC in vitro. In vivo, the addition of M2M-derived SEVs or overexpression of circUbe3a significantly exacerbated myocardial fibrosis after acute myocardial infarction, and these effects were partially abolished by circUbe3a-specific shRNA. Conclusions: Our findings suggest that M2M-derived circUbe3a-containing SEVs promote the proliferation, migration, and phenotypic transformation of CFs by directly targeting the miR-138-5p/RhoC axis, which may also exacerbate myocardial fibrosis after acute myocardial infarction.

CircHIPK3 regulates the autophagy and apoptosis of hypoxia/reoxygenation-stimulated cardiomyocytes via the miR-20b-5p/ATG7 axis.

Autophagy and apoptosis are involved in myocardial ischemia/reperfusion (I/R) injury. Research indicates that circular RNA HIPK3 (circHIPK3) is crucial to cell autophagy and apoptosis in various cancer types. However, the role of circHIPK3 in the regulation of cardiomyocyte autophagy and apoptosis during I/R remains unknown. Our study aimed to examine the regulatory effect of circHIPK3 during myocardial I/R and investigate its mechanism in cardiomyocyte autophagy and apoptosis. Methods and results. The expression of circHIPK3 was upregulated during myocardial I/R injury and hypoxia/reoxygenation (H/R) injury of cardiomyocytes. To study the potential role of circHIPK3 in myocardial H/R injury, we performed gain-of-function and loss-of-function analyses of circHIPK3 in cardiomyocytes. Overexpression of circHIPK3 significantly promoted H/R-induced cardiomyocyte autophagy and cell injury (increased intracellular reactive oxygen species (ROS) and apoptosis) compared to those in the control group, while silencing of circHIPK3 showed the opposite effect. Further research found that circHIPK3 acted as an endogenous miR-20b-5p sponge to sequester and inhibit miR-20b-5p activity, resulting in increased ATG7 expression. In addition, miR-20b-5p inhibitors reversed the decrease in ATG7 induced by silencing circHIPK3. Conclusions. CircHIPK3 can accelerate cardiomyocyte autophagy and apoptosis during myocardial I/R injury through the miR-20b-5p/ATG7 axis. These data suggest that circHIPK3 may serve as a potential therapeutic target for I/R.

Qiliqiangxin alleviates Ang II-induced CMECs apoptosis by downregulating autophagy via the ErbB2-AKT-FoxO3a axis.

Our previous work revealed the protective effect of Qiliqiangxin (QLQX) on cardiac microvascular endothelial cells (CMECs), but the underlying mechanisms remain unclear. We aimed to investigate whether QLQX exerts its protective effect against high-concentration angiotensin II (Ang II)-induced CMEC apoptosis through the autophagy machinery. CMECs were cultured in high-concentration Ang II (1 µM) medium in the presence or absence of QLQX for 48 h. We found that QLQX obviously inhibited Ang II-triggered autophagosome synthesis and apoptosis in cultured CMECs. QLQX-mediated protection against Ang II-induced CMEC apoptosis was reversed by the autophagy activator rapamycin. Specifically, deletion of ATG7 in cultured CMECs indicated a detrimental role of autophagy in Ang II-induced CMEC apoptosis. QLQX reversed Ang II-mediated ErbB2 phosphorylation impairment. Furthermore, inhibition of ErbB2 phosphorylation with lapatinib in CMECs revealed that QLQX-induced downregulation of Ang II-activated autophagy and apoptosis was ErbB2 phosphorylation-dependent via the AKT-FoxO3a axis. Activation of ErbB2 phosphorylation by Neuregulin-1ß achieved a similar CMEC-protective effect as QLQX in high-concentration Ang II medium, and this effect was also abolished by autophagy activation. These results show that the CMEC-protective effect of QLQX under high-concentration Ang II conditions could be partly attributable to QLQX-mediated ErbB2 phosphorylation-dependent downregulation of autophagy via the AKT-FoxO3a axis.

Hypoxia-reoxygenation induces macrophage polarization and causes the release of exosomal miR-29a to mediate cardiomyocyte pyroptosis.

To investigate the mechanism by which hypoxia-reoxygenation (HR) mediates macrophage polarization to the M1 phenotype and then mediates cardiomyocyte (CM) pyroptosis through exosome release. Mouse bone marrow macrophages and CMs were cultured in vitro under hypoxia for 12 h and reoxygenation for 6 h to establish an HR cell model. qPCR was used to detect the M1 or M2 macrophage markers IL-1ß, TNF-α, MR, and Arg, and a macrophage and CM coculture system was then established. Macrophages were transfected with an exosome-CD63-red fluorescent protein (RFP) lentivirus, allowing secretion of exosomes expressing RFP, and GW4869 was used to inhibit exosome release by macrophages. qPCR detected miR-29 expression in macrophage-derived exosomes, and macrophages were transfected with miR-29a inhibitors to obtain exosomes with low miR-29a expression (siR-exos). Pyroptosis indicators were detected by Western blot and ELISA. Importantly, LPS induced bone marrow macrophage polarization to the M1 type as a positive control to further verify that these exosomes (LPS-exos) regulated CM pyroptosis by delivering miR29a. Dual luciferase reporter and Western blot assays were adopted to analyze the miR-29a and MCL-1 target relationship. In addition, MCL-1 overexpression was used as a rescue experiment to determine whether miR-29a regulates pyroptosis in CM by targeting MCL-1. Macrophages expressed the M1 macrophage markers IL-1ß and TNF-α after HR exposure. After CM coculture, RFP expression was significantly higher in the HR group than in the normal (Nor) group but significantly reduced in the GW4869 group. Immunofluorescence showed that caspase-1 mRNA and protein expression in the HR group was significantly higher than that in the Nor group (P < 0.05). Caspase-1 expression was significantly decreased in the GW4869 group compared with the HR group (P < 0.05). Western blotting showed that the pyrolysis-related NLRP3 and ASC protein expression levels were significantly upregulated in the HR group compared with the control (Ctr) and Nor groups (P < 0.05). However, GW4869 effectively inhibited pyroptosis-related protein expression (P < 0.05). In addition, ELISA showed that the expression of the inflammation indicators IL-1ß and IL-18 was significantly increased in the HR group compared to the Ctr group (P < 0.05) but decreased in the GW4869 group (P < 0.05). qPCR showed that miR-29a was upregulated in the HR group compared to the Nor group. Moreover, HR-induced exosomes (HR-exos) from macrophages exacerbated HR-induced CM pyroptosis, while inhibition of miR-29a in exosomes partially offset CM pyroptosis induction. LPS-exos promoted pyroptosis-related protein expression, as the IL-1ß and IL-18 concentrations were increased in the LPS-exos group. However, pyroptosis-related proteins were observably decreased, and IL-1ß and IL-18 were also significantly decreased after miR-29a inhibition when compared with that in the HR-exos and LPS-exos groups. Mcl-1 overexpression reversed miR-29a-mediated CM pyroptosis in an HR environment. HR treatment induced macrophage polarization towards the M1 phenotype, which mediated CM pyroptosis through exosomal miR-29a transfer by targeting MCL-1.

Proline-rich protein 11 overexpression is associated with a more aggressive phenotype and poor overall survival in ovarian cancer patients.

BACKGROUND: The proline-rich protein 11 (PRR11) is a newly identified oncogene associated with a poor prognosis in several human cancers. Nonetheless, research on its role in ovarian cancer (OC) remains largely understudied. Therefore, this study aims to evaluate the expression levels of PRR11 protein and its role in human ovarian cancer. METHODS: Immunohistochemistry analysis was used to evaluate the expression levels of PRR11 protein in human samples obtained from 49 patients diagnosed with OC and subjected to curative surgery in the First Affiliated Hospital of Wenzhou Medical University between 2007 and 2015. RESULTS: In total, 57.1% of the primary OC tumor tissue evaluated demonstrated overexpression of PRR11. Meanwhile, the survival analysis showed that the overall survival (OS) of patients presenting overexpression of PRR11 was significantly lower than the OS of the patients with negative PRR11. In subsequent experiments, it was found that silencing the expression of PRR11 expression inhibited the proliferation of tumor cells and the migration of cells in vitro. Further, cells subjected to PRR11 knockdown exhibited a decrease in tumor growth in vivo. The downregulation of PRR11 was coupled with a decrease in N-cadherin and downregulation in the expression of early growth response protein 1 (EGR1). CONCLUSIONS: The findings suggest that PRR11 might be considered as a potential target for prognostic assessment and gene therapy strategies for patients diagnosed with OC.