Search

Adipose-derived mesenchymal stem cells (adMSCs) are suggested as potential tools for the treatment of regenerative diseases, including tissue repair. This study aimed to explore the function of adMSC-derived apoptotic bodies in skin wound healing and the molecules of action.The acquired adMSCs and their-derived apoptotic bodies were identified. A murine model of full-thickness skin wounds was treated with apoptotic bodies. The wound healing process of mice and the pathological changes in wound tissues were examined. Ana-1 macrophages were treated with lipopolysaccharide (LPS) and apoptotic bodies for in vitro experiments. Polarization of macrophages was examined by immunofluorescence staining of the specific biomarkers and ELISA kits. Dermal microvascular endothelial cells (DMECs) or dermal fibroblasts (DFs) were co-cultured with apoptotic bodies or the LPS- and apoptotic bodies-treated Ana-1 cells. Downstream molecules mediated by apoptotic bodies were screened by microarray and bioinformatic analyses.Apoptotic bodies treatment accelerated skin wound healing in mice and promoted formation of granulation tissues and blood vessels in wound tissues. Apoptotic bodies treatment induced M2 polarization of macrophages. The angiogenesis ability of DMECs, and the viability and migration of DFs were increased when co-cultured with the apoptotic bodies-treated Ana-1 cells. MicroRNA (miR)-21-5p was abundantly expressed in ABs, and kruppel like factor 6 (KLF6) mRNA was confirmed as a target of miR-21-5p. Overexpression of KLF6 reduced M2 polarization of macrophages and blocked the promoting effect of apoptotic bodies on wound healing in vitro and in vivo.miR-21-5p carried by adMSC-derived apoptotic bodies targets KLF6 to induce M2 polarization of macrophages and augment skin wound healing.

Trophoblast cell differentiation is of paramount importance for successful pregnancy. Krüppel-like factor 6 (KLF6), a transcription factor with diverse roles in cell physiology and tumor biology, is required for trophoblast differentiation through the syncytial pathway. Herein, we demonstrate that extravillous trophoblast (EVT) cell migration and mesenchymal phenotype are increased upon KLF6 downregulation or the expression of a deletion mutant lacking its transcriptional regulatory domain (KΔac). Raman spectroscopy revealed molecular modifications compatible with increased differentiation in cells stably expressing the KΔac mutant. Moreover, abnormally invasive placenta showed lower KLF6 immunostaining compared with the normal placenta. Thus, impaired KLF6 expression or function stimulates EVT migration and differentiation in vitro and may contribute to the physiopathology of the abnormally invasive placenta.

Based on the emerging role of Kruppel-like factor 6 (KLF6) in lipid metabolism, we examined whether there is a relationship between the KLF6 rs3750861 genetic variant and plasma ceramide levels in people with type 2 diabetes mellitus (T2DM).We measured six previously identified plasma ceramides, which have been associated with increased cardiovascular risk [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)] amongst 101 Caucasian post-menopausal women with T2DM, who consecutively attended our diabetes outpatient service during a 3-month period. Plasma ceramides were measured by targeted liquid chromatography-tandem mass spectrometry assay. Genotyping of the KLF6 rs3750861 polymorphism was performed by TaqMan-Based RT-PCR system. Overall, 87 (86.1%) patients had KLF6 rs3750861 C/C genotype and 14 (13.9%) had C/T or T/T genotypes. After adjustment for age, diabetes-related variables, use of lipid-lowering drugs and other potential confounders, patients with C/T or T/T genotypes had higher plasma Cer(d18:1/18:0) (0.159 ± 0.05 vs. 0.120 ± 0.04 μmol/L, p = 0.012), Cer(d18:1/20:0) (0.129 ± 0.04 vs. 0.098 ± 0.03 μmol/L, p = 0.008), and Cer(d18:1/24:1) (1.236 ± 0.38 vs. 0.978 ± 0.36 μmol/L, p = 0.032) compared with those with C/C genotype.The C/T or T/T genotypes of rs3750861 in the KLF6 gene were closely associated with higher levels of specific plasma ceramides in post-menopausal women with T2DM.

Super-enhancer consists of a large cluster of transcription enhancers that regulates the expression of genes playing an important role in the growth and development of malignant tumors. Recently, several attempts for the identification of super-enhancers have been made, but their functional role in tumor cells remains unclear. This paper aims at elucidating the functional properties of KLF6 super-enhancer related to the growth regulation of HepG2 cells, in relation to transcription factors (TFs). First, some TFs specifying KLF6 super enhancer were identified using CRISPR/Cas9 system and siRNA. Then, their effects on the expression of the target gene KLF6 were assessed. Last, their influence on the proliferation of tumor cells was considered using the MTT method. The study shows that the active enhancers of KLF6 super-enhancer recruit GATA2 and SOX10 TFs to control the expression of the target gene, KLF6. Our findings suggest that the activity of KLF6 super-enhancer is regulated by two TFs (GATA2 and SOX10), and its targeting may be a potential therapeutic strategy for the liver cancer therapy.

Long non-coding RNA (lncRNA) ZFAS1 (zinc finger antisense 1) was demonstrated to play critical roles in various cancer progression. However, the functions of ZFAS in cervical cancers (CC) are unclear. Human CC cell lines were used for in vitro experiments. RT-qPCR (Real Time Quantitative PCR) was performed to detect the expression of ZFAS1, microRNA-190a-3p (miR-190a-3p) and Kruppel-like factor 6 (KLF6). Cell proliferation, invasion and migration assays were used to investigate biological behaviors of CC cells related to CC progression. The relationship of KLF6 to ZFAS1 and miR-190a-3p was analyzed by circRIP and luciferase reporter assay. In addition, in vivo experiment was carried out to explore the function of ZFAS1 in tumor growth of CC. The expression levels of ZFAS1 and KLF6 were both significantly elevated, while the expression of miR-190a-3p was inhibited in CC tumor tissues. In addition, ZFAS1 influenced CC tumor growth through miR-190a-3p. KLF6 was a target of miR-190a-3p and inhibited miR-190a-3p-induced CC tumor growth. Furthermore, KLF6 was negatively regulated by miR-190a-3p, but positively regulated by ZFAS1. Overexpression of ZFAS1 and inhibition of miR-190a-3p significantly increased the expression levels of KLF6. Finally, in vitro assays demonstrated that inhibition of ZFAS1 reduced CC tumor growth and the expression levels of KLF6, but increased the expression levels of miR-190a-3p. ZFAS1 could regulate CC pathogenesis via regulating the miR-190a-3p/KLF6 axis, which might be considered as new CC therapeutic targets.

Marbling influences the taste and tenderness of meat and is the main determinant of carcass quality in many countries. This study aims to investigate the influence of KLF6 (Kruppel Like Factor 6) and associated molecular mechanisms on lipid metabolism in bovine adipocytes. In the current study, KLF6 gene expression was down regulated via siRNA (small interfering RNA) in bovine adipocytes in vitro. Subsequently, adipogenic cells were collected from the culture media after 9 days, and subjected to fluorescent imaging and RNA sequencing. After confirming that KLF6 was down regulated in bovine adipocytes by siRNA, differential gene expression analysis was used to characterize the infuence of KLF6 on gene expression profiles in bovine adipocytes. A total of 10,812 genes were characterized as differentially expressed genes (DEGs) of which, 109 were up-regulated and 62 were down-regulated genes. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis identified that the DEGs were associated with lipid metabolism, carbohydrate metabolism, cell growth and death, cancer, and the signaling pathways for calcium, AMPK (Adenosine Monophosphate-Activated Protein Kinase), PI3K-Akt (Phosphatidylinositol 3-kinase), PPAR (Peroxisome proliferator-activated receptors), MAPK (mitogen-activated protein kinase), cAMP (Cyclic adenosine monophosphate), and Wnt (Wingless-related integration site). Similarly, gene ontology analysis indicated that down-regulation of KLF6 gene significantly up regulated the genes that regulate adipogenesis, differentiation and regulation of adipocytes and homeostasis of bovine adipocytes, specifically regulating the cell-type specific apoptotic action, negative regulation of apoptotic pathways, programmed cell death, and growth. Results indicate that KLF6 has a role in regulating lipid metabolism in bovine adipocytes. These findings provide evidence that may inform further investigations into molecular mechanisms that underlie the role of bovine KLF6 gene in regulating adipogenesis.

Background: As a member of the Krüppel-like factor (KLFs) family, Krüppel-like factor 6 (KLF6) plays a critical role in regulating key cellular functions. Presently, scholars have proved the important role of KLF6 in the tumorigenesis of certain cancers through a large number of experiments. However, gaps still remain in our knowledge of the role of KLF6 in pancreatic cancer (PAAD). Therefore, this paper mainly investigates the role of KLF6 in the progression of pancreatic cancer. Methods: The expression pattern of KLF6 in pancreatic cancer was explored in pancreatic cancer tissues and cell lines. Then, we investigated the prognostic value of KLF6 in pancreatic cancer by immunohistochemical assays. Next, Cell Counting Kit-8 (CCK8) and clone information assays were employed to explore the proliferation of PAAD affected by KLF6. The metastasis and epithelial-mesenchymal transition (EMT) abilities affected by KLF6 were identified through transwell invasion as well as migration assays and western blots. Finally, the TRRUST tool was used to analyze the potential targeted genes of KLF6. The results were verified by Quantificational Real-time Polymerase Chain Reaction (qRT-PCR), western blot and rescue assays. Results: KLF6 expresses lowly in pancreatic cancer compared to corresponding normal tissues and relates to poor survival times. Overexpression of KLF6 inhibits the proliferation, metastasis, and EMT progression in pancreatic cancer cells. Further studies suggest that KLF6 could upregulate ATF3 in PAAD. Conclusions: Our results suggest that KLF6 can be a useful factor in predicting the prognosis of PAAD patients and that it inhibits the progression of pancreatic cancer by upregulating activating transcription factor 3 (ATF3).

Background Colorectal cancer (CRC) is one of the most important cancers in the world, and its prevalence varies depending on the geographical area. Genetically, tumor regeneration in CRC as a multi-step process involves activating mutations in protocogenes and losing the function of tumor suppressor genes as well as DNA repair and recovery genes. Occur in this way, our goal was to investigate the expression of KLF6 genes as a tumor suppressor and MUTYH involved in the DNA repair process in colorectal cancer. Methods This research was conducted during the years 2019–2018 in Razi Hospital, Rasht. The subjects included 30 tumoral and 30 non-tumoral tissues of colorectal cancer and 20 healthy controls. The real-time PCR method was used to investigate the gene expression. For data analysis by SPSS, parametric statistical tests ANOVA and T test and regression analysis were used and p value values less than 0.05 were considered significant. Results The expression of KLF6 gene in tumoral tissues showed a significant decrease compared to non-tumoral tissues (P = 0.04). Also, the expression of MUTYH gene in tumor tissue showed a significant decrease compared to non-tumoral (P = 0.02) and this decrease in MUTYH gene expression had a significant relationship with increasing tumor stage (P = 0.01). Conclusion These findings suggest that decreased expression of KLF6 and MUTYH genes in the study population has a significant relationship with colorectal cancer and can be considered as tumor marker in diagnostic purpose.

Ischemic stroke (IS), caused by a permanent or transient local reduction in blood supply to the brain, is one of the most widespread causes of public health problems in modern society. Long non-coding RNA (LncRNA) has been reported to be related to angiogenesis following IS. In this study, we explored the effect and potential molecular mechanism of lncRNA HOTAIR in IS. Permanent middle cerebral artery occlusion (pMCAO) model and oxygen and glucose deprivation (OGD) model were established. HOTAIR was increased in vivo and in vitro models post-ischemic. HOTAIR knockdown promoted neurological function recovery, manifesting in decreased modified neurological severity score, cerebral infarcted area, apoptosis and inflammation, and improved balance ability, spatial learning and memory ability. Silencing HOTAIR also improved the viability of OGD-induced N2a cells, and attenuated apoptosis and inflammation. HOTAIR can compete with KLF6 to bind to miR-148a-3p. miR-148a-3p knockdown or KLF6 overexpression partially reversed the effect of sh-HOTAIR on OGD-induced N2a cells. HOTAIR suppressed the activation of STAT3 pathway via the miR-148a-3p/KLF6 axis. To summarize, this study demonstrated that lncRNA HOTAIR absorbed miR-148a-3p and up-regulate KLF6 expression through ceRNA mechanism, and inhibited STAT3 pathway, promoted apoptosis and inflammation, and aggravated neurological injury post-IS.

Background Gastric cell carcinoma (GCC) is a common and high-incidence malignant gastrointestinal cancer that seriously threatens human life and safety. Evidences suggest that microRNAs (miRNAs) exhibit an essential role in regulating the occurrence and development of GCC, while the effects and possible mechanisms remain to be further explored. Objective This study was designed to explore whether miR-200c-3p exerted its functional role in the growth and metastasis of GCC, and investigate the possible mechanisms. Methods The expression levels of miR-200c-3p in GCC tissues and cell lines were detected by qRT-PCR analysis. The functional role of miR-200c-3p in the viability, proliferation, migration and invasion of GCC cells were evaluated by CCK-8, EdU, wound healing and Transwell assays. In addition, the candidate targets of miR-200c-3p was predicted and confirmed by dual-luciferase reporter assay. Moreover, the relationship between miR-200c-3p and target (Krüppel like factor 6, KLF6) was assessed by qRT-PCR and western blot assays. Besides, the expression levels of KLF6 in GCC cells were determined by qRT-PCR and western blot assays. Furthermore, the role of KLF6 in the viability, proliferation, migration and invasion of GCC cells mediated with miR-200c-3p mimics was evaluated by CCK-8, EdU, wound healing and Transwell assays. Results In the present study, a new tumor promoting function of miR-200c-3p was disclosed in GCC. We found that the expression of miR-200c-3p was obviously increased in clinic GCC tissues and cell lines. In addition, down-regulation of miR-200c-3p suppressed cell viability, proliferation, migration, and invasion in GCC cells. Moreover, KLF6 was verified as a direct target of miR-200c-3p by binding its 3’-UTR. Additionally, KLF6 was remarkably decreased and was negatively associated with the miR-200c-3p expression in GCC cell lines. Furthermore, over-expression of KLF6 retarded the effects of miR-200c-3p on the growth and metastasis of GCC cell lines. Conclusions MiR-200c-3p potentially played a tumor-promoting role in the occurrence and development of GCC, which may be achieved by targeting KLF6. Graphic abstract

To investigate the effect of SPARC gene overexpression on the chemotherapeutic sensitivity of AML-MDS cell line SKM-1 to Ara-C and to further explore its mechanism.Subjects were divided into 6 groups: SKM-1 cells (Control), Negative control (LV-NC), SPARC overexpression (LV-SPARC), SKM-1 cells+30 ng/ml Ara-C (30 ng/ml Ara-C), LV-NC+30 ng/ml Ara-C and LV-SPARC+30 ng/ml Ara-C. Cell activity was detected by CCK-8 assay, cell cycle distribution and apoptosis were detected by flow cytometry, mRNA expression levels of SPARC, CPBP and MLKL were detected by RT-qPCR, and the expression levels of related protein were detected by Western blot.After co-treatment with SPARC overexpression and Ara-C, the cell viability decreased and apoptosis increased significantly, with obvious up-regulation of Bax and down-regulation of BCL-2 (P0.05). Compared with the control group, the cell cycle of LV-SPARC+30 ng/ml Ara-C group was significantly arrested in S phase with obvious down-regulation of CDK2 and up-regulation of p27SPARC overexpression enhanced the sensitivity of SKM-1 cells to Ara-C and promoted cell cycle arrest and apoptosis, the mechanism of which may be related to the regulation of CPBP/MLKL pathway.SPARC过表达通过调控CPBP/MLKL增强SKM-1细胞对Ara-C的敏感性.探讨SPARC基因过表达对AML-MDS细胞株SKM-1阿糖胞苷（Ara-C）化疗敏感性的影响及调控机制。.该实验分为正常SKM-1细胞（对照）、空载（LV-NC）、SPARC过表达（LV-SPARC）、SKM-1细胞+30 ng/ml Ara-C（30 ng/ml Ara-C）、LV-NC+30 ng/ml Ara-C和LV-SPARC+30 ng/ml Ara-C共6组。采用CCK-8法检测细胞活性，流式细胞术检测细胞周期分布和凋亡，RT-qPCR检测各组细胞SPARC、CPBP和MLKL的mRNA表达水平，Western blot检测相关蛋白表达水平。.SPARC过表达和Ara-C共处理后，细胞活性明显降低，细胞凋亡率明显增高，BCL-2蛋白表达水平显著降低，Bax蛋白表达水平显著增高（P0.05）。与对照组相比，LV-SPARC+30 ng/ml Ara-C组的细胞周期明显阻滞于S期，CDK2表达水平显著降低，p27SPARC过表达增强了SKM-1细胞对Ara-C的敏感性，促进了细胞周期阻滞和细胞凋亡能力，其机制可能与调控CPBP/MLKL途径相关。.

Breast cancer (BC) is the most commonly occurring malignancy in women. This study aimed to investigate the functions of the long noncoding RNA ZBED3‐AS1 (ZBED3‐AS1) in BC and its molecular mechanisms. qRT‐PCR was conducted to access the expression of ZBED3‐AS1, microRNA‐513a‐5p (miR‐513a‐5p), and Kruppel like factor 6 (KLF6) in BC. Additionally, BC cell viability and proliferative capacity were measured by MTT and 5‐Ethynyl‐20‐deoxyuridine (EdU) assays. A transwell assay was used for evaluating BC cell migration and invasion. The interactions among ZBED3‐AS1, miR‐513a‐5p, and KLF6 in BC were confirmed by dual‐luciferase reporter assay. Furthermore, feedback approaches were performed to determine whether ZBED3‐AS1 influences BC cell behaviors by regulating the miR‐513a‐5p/KLF6 axis. The murine xenograft model was established to assess the effect of ZBED3‐AS1 on tumor growth. The expression of ZBED3‐AS1 and KLF6 was reduced, while miR‐513a‐5p expression was elevated in BC. ZBED3‐AS1 elevation attenuated the malignant behaviors of BC cells, including viability, proliferative capacity, migration, and invasion. Mechanical experiments revealed that ZBED3‐AS1 targeted miR‐513a‐5p, and miR‐513a‐5p targeted KLF6 in BC. Feedback approaches validated that miR‐513a‐5p overexpression or KLF6 depletion reversed the inhibitory effects of ZBED3‐AS1 upregulation on viability, proliferative capacity, migration, and invasion of BC cells. Furthermore, ZBED3‐AS1 elevation attenuated the tumor growth in the murine xenograft model. ZBED3‐AS1 hindered the malignant development of BC cells by regulating the miR‐513a‐5p/KLF6 axis, providing a novel therapeutic target in BC., Diagrammatic sketch of the lncRNA ZBED3‐AS1‐miR‐513‐3p‐KLF6 axis in the breast.

Atherosclerosis (AS) is the main pathological basis for ischemic cardiovascular and cerebrovascular diseases. Mesenchymal stem cell (MSC)-derived exosomes have the potential to alleviate AS, while the underlying mechanism remains unclear. Here, we aimed to investigate the mechanism of MSC-derived exosomes in AS. The AS mouse model was prepared by feeding ApoE-/- mice with high-fat diet. AS mice were administered with MSC-derived exosomes, and the atherosclerotic plaque area was analyzed by Oil Red O staining. Mouse RAW264.7 macrophages were incubated with MSC-derived exosomes. The macrophage infiltration, macrophage proportion, and cell migration were estimated by immunohistochemistry, flow cytometry, or Transwell assay. The relationship between miR-21a-5p and kruppel-like factor 6 (KLF6) or extracellular signal-regulated protein kinases 2 (ERK2) was verified by luciferase reporter assay. We found that MSC-derived exosomes promoted M2 polarization of macrophages and reduced plaque area and macrophage infiltration in AS mice. miR-21a-5p overexpression caused an increase of M2 macrophages in RAW264.7 cells and led to a decrease in migration of RAW264.7 cells. Moreover, both KLF6 and ERK2 are the targets of miR-21a-5p. MSC-derived exosomes containing miR-21a-5p promoted M2 polarization of RAW264.7 cells by suppressing KLF6 expression. MSC-derived exosomes containing miR-21a-5p inhibited migration of RAW264.7 cells through inhibiting the ERK1/2 signaling pathway. In conclusion, MSC-derived exosomes containing miR-21a-5p promote macrophage polarization and reduce macrophage infiltration by targeting KLF6 and ERK1/2 signaling pathways, thereby attenuating the development of AS. Thus, MSC-derived exosomes may be a promising treatment for AS.

Purpose To analyse the relationship between the transcriptional expression of Kruppel-like factor-6 (KLF6) and local response to treatment with radiotherapy in patients with head and neck squamous cell carcinoma (HNSCC). Methods We determined the transcriptional expression of KLF6 in tumour biopsies obtained before treatment with radiotherapy in 83 HNSCC patients. The KLF6 expression was categorized according to the local control of the disease with a recursive partitioning analysis. Results During the follow-up period, 27 patients (32.5%) had a local recurrence of the tumour. Patients with local recurrence had significantly higher levels of KLF6 expression than patients in which radiotherapy achieved local control of the disease (P = 0.029). Five-year local recurrence-free survival for patients with a high transcriptional expression of KLF6 (n = 46) was 51.1% (95% CI 36.4-66.2%), and for patients with low expression it was 85.6% (95% CI 73.9-97.3%) (P = 0.0001). The results of a multivariate analysis showed that patients with a high KLF6 expression had a 3.8 times higher risk of local recurrence after treatment with radiotherapy (95% CI 1.4-10.5, P = 0.008). Conclusion Transcriptional expression of KLF6 was significantly related to local control in HNSCC patients treated with radiotherapy. Patients with high levels of KLF6 expression had a significantly higher risk of local recurrence after treatment.

Background Despite emerging evidence on the therapeutic potential of mesenchymal stem cells (MSCs) for liver fibrosis, the underlying mechanisms remain unclear. At present, MSC-derived exosomes (MSC-EXOs) are widely accepted as crucial messengers for intercellular communication. This study aimed to explore the therapeutic effects of MSC-EXOs on liver fibrosis and identify the mechanisms underlying the action of MSC-EXOs. Methods Carbon tetrachloride was used to induce a liver fibrosis model, which was intravenously administered with MSCs or MSC-EXOs to assess treatment efficacy. The resulting histopathology, fibrosis degree, inflammation and macrophage polarization were analyzed. RAW264.7 and BMDM cells were used to explore the regulatory effects of MSC-EXOs on macrophage polarization. Then, the critical miRNA mediating the therapeutic effects of MSC-EXOs was screened via RNA sequencing and validated experimentally. Furthermore, the target mRNA and downstream signaling pathways were elucidated by luciferase reporter assay, bioinformatics analysis and western blot. Results MSCs alleviated liver fibrosis largely depended on their secreted exosomes, which were visualized to circulate into liver after transplantation. In addition, MSC-EXOs were found to modulate macrophage phenotype to regulate inflammatory microenvironment in liver and repair the injury. Mechanically, RNA-sequencing illustrates that miR-148a, enriched in the MSC-EXOs, targets Kruppel-like factor 6 (KLF6) to suppress pro-inflammatory macrophages and promote anti-inflammatory macrophages by inhibiting the STAT3 pathway. Administration of miR-148a-enriched MSC-EXOs or miR-148a agomir shows potent ameliorative effects on liver fibrosis. Conclusions These findings suggest that MSC-EXOs protect against liver fibrosis via delivering miR-148a that regulates intrahepatic macrophage functions through KLF6/STAT3 signaling and provide a potential therapeutic target for liver fibrosis.

Transcription factors (TFs) act as powerful levers to regulate neural physiology and can be targeted to improve cellular responses to injury or disease. Because TFs often depend on cooperative activity, a major challenge is to identify and deploy optimal sets. Here we developed a bioinformatics pipeline, centered on TF co-occupancy of regulatory DNA, and used it to predict factors that potentiate the effects of pro-regenerative Klf6 in vitro. High content screens of neurite outgrowth identified cooperative activity by 12 candidates, and systematic testing in a mouse model of corticospinal tract (CST) damage substantiated three novel instances of pairwise cooperation. Combined Klf6 and Nr5a2 drove the strongest growth, and transcriptional profiling of CST neurons identified Klf6/Nr5a2-responsive gene networks involved in macromolecule biosynthesis and DNA repair. These data identify TF combinations that promote enhanced CST growth, clarify the transcriptional correlates, and provide a bioinformatics approach to detect TF cooperation., After injury to the nervous system, many neurons fail to initiate transcriptional programs needed for axon growth. Here the authors examine co-operative binding of factors to regulatory DNA to predict combinations that improve axon growth when ectopically co-expressed.

AIM To investigate the potential role of Kruppel-like factor 6 (KLF6) in the odontoblastic differentiation of immortalized dental papilla mesenchymal cells (iMDP-3) cells. METHODOLOGY Alizarin Red S (ARS) and Alkaline phosphatase (ALP) staining was used to examine the mineralization effect of iMDP-3 cells after odontoblastic induction. Real-time PCR and Western blotting were employed to analyse dentine sialophosphoprotein (DSPP), dentine matrix protein 1 (DMP1), RUNX family transcription factor 2 (RUNX2), ALP and KLF6 expression during this process. Co-expression of the KLF6 with DMP1, DSPP and RUNX2 was detected by double immunofluorescence staining to explore their local relationship in the cell. To further investigate KLF6 functions, Klf6 gain- and loss-of-function assays followed by ARS and ALP stainings, real-time PCR and Western blotting were performed using Klf6-overexpression plasmids and Klf6 siRNA to investigate whether changes in Klf6 expression affect the odontoblastic differentiation of iMDP-3 cells. Dual-luciferase reporter assays were used to elucidate the mechanistic regulation of Dspp and Dmp1 expression by Klf6. Means were compared using the unpaired t-test and Kruskal-Wallis one-way anova with P

Background & Aims Hypoxia inducible factors (HIFs) are a hallmark of inflammation and are key regulators of hepatic immunity and metabolism, yet their role in HBV replication is poorly defined. HBV replicates in hepatocytes within the liver, a naturally hypoxic organ, however most studies of viral replication are performed under conditions of atmospheric oxygen, where HIFs are inactive. We therefore investigated the role of HIFs in regulating HBV replication. Methods Using cell culture, animal models, human tissue and pharmacological agents inhibiting the HIF-prolyl hydroxylases, we investigated the impact of hypoxia on the HBV life cycle. Results Culturing liver cell-based model systems under low oxygen uncovered a new role for HIFs in binding HBV DNA and activating the basal core promoter, leading to increased pre-genomic RNA and de novo HBV particle secretion. The presence of hypoxia responsive elements among all primate members of the hepadnaviridae highlights an evolutionary conserved role for HIFs in regulating this virus family. Conclusions Identifying a role for this conserved oxygen sensor in regulating HBV transcription suggests that this virus has evolved to exploit the HIF signaling pathway to persist in the low oxygen environment of the liver. Our studies show the importance of considering oxygen availability when studying HBV-host interactions and provide innovative routes to better understand and target chronic HBV infection. Lay summary Viral replication in host cells is defined by the cellular microenvironment and one key factor is local oxygen tension. Hepatitis B virus (HBV) replicates in the liver, a naturally hypoxic organ. Hypoxia inducible factors (HIFs) are the major sensors of low oxygen; herein, we identify a new role for these factors in regulating HBV replication, revealing new therapeutic targets., Graphical abstract, Highlights • Primate hepadnaviridae encode conserved hypoxia response elements. • Hypoxia inducible factors bind HBV DNA and activate the basal core promoter. • Pharmacological stabilization of hypoxia inducible factors and low oxygen increases HBV transcription and particle genesis. • Knockdown studies show a role for both HIF-1α and HIF-2α in regulating HBV transcription.

Krüppel-like transcription factor 6 (KLF6) is a ubiquitous tumor suppressor gene involved in regulating cell growth, proliferation, differentiation and angiogenesis. The objective of the study was to investigate the clinical and prognostic significance of KLF6 expression in cutaneous malignant melanoma (CMM) patients. A total of CMM 67 patients were enrolled in this study. The specimens were evaluated by immunohistochemistry to detect KLF6. The positive KLF6 expression in CMM tissues was significantly lower than in normal skin tissues (p0.01).The presence of KLF6 in CMM was correlated with ulceration (p0.01), lymph node metastasis (p0.01) and clinical stage (p0.01). The overall 5-year survival rate of the 67 patients was 13.4%. The 5-year survival rate of patients with negative KLF6 expression was correlated with KLF6 expression (p0.01), ulceration (p0.01), lymph node metastasis (p0.01), clinical stage (p0.01) and operation type (p0.01). Ulceration and clinical staging were independent relevant factors. In conclusion, the presence of KLF6 in CMM was correlated with ulceration, lymph node metastasis, clinical stage and poor prognosis.

Placental extravillous trophoblasts play a crucial role in the establishment of a healthy pregnancy. Reactive oxygen species (ROS) may contribute to their differentiation and function as mediators in signaling processes or might cause oxidative stress resulting in trophoblast dysfunction. The krüppel-like transcription factor 6 (KLF6) regulates many genes involved in essential cell processes where ROS are also involved. However, whether KLF6 regulates ROS levels has not been previously investigated.KLF6 was silenced by siRNAs in HTR8-SV/neo cells, an extravillous trophoblast model. Total and mitochondrial ROS levels, as well as mitochondrial membrane potential and apoptosis were analyzed by flow cytometry. The expression of genes and proteins of interest were analyzed by qRT-PCR and Western blot, respectively. Cell response to oxidative stress, proliferation, viability, morphology, and migration were evaluated.KLF6 downregulation led to an increase in ROS and NOX4 mRNA levels, accompanied by reduced cell proliferation and increased p21 protein expression. Catalase activity, 2-Cys peroxiredoxin protein levels, Nrf2 cytoplasmic localization and hemoxygenase 1 expression, as well as mitochondrial membrane potential and cell apoptosis were not altered suggesting that ROS increase is not associated with cellular damage. Instead, KLF6 silencing induced cytoskeleton modifications and increased cell migration in a ROS-dependent manner.Present data reveal a novel role of KLF6 on ROS balance and signaling demonstrating that KLF6 downregulation induces an increase in ROS levels that contribute to extravillous trophoblast cell migration.

Objective. To explore the effect of circular RNA circ-ABCB10 on the proliferation and apoptosis of laryngeal carcinoma via inhibiting KLF6. Methods. RT-qPCR assay was adopted to detect the expression of circ-ABCB10 and KFL6 in laryngeal carcinoma tissues and cell lines. Cell counting kit-8 (CCK-8) and clone formation assay were employed to detect laryngeal cancer cell viability and proliferation when circ-ABCB10 was silenced or upregulated. In this study, the apoptosis rate was detected by flow cytometry and the protein expression was detected by Western blotting. Wound healing and cross-hole invasion were used to study the migration and invasion of laryngeal cancer cells when circ-ABCB10 was silenced or upregulated. Results. The results of RT-qPCR detection indicated that the expression of circ-ABCB10 in all three laryngeal carcinoma cells was downregulated by 3.2 times compared with that of HaCat cells. There is low expression of circ-ABCB10 in most laryngeal carcinoma tissues, the diagnostic cutoff value of circ-ABCB10 is 0.0008, the area under the curve is 0.718, the sensitivity is 0.981, and the specificity is 0.556. The expression level of KLF6 in laryngeal carcinoma is on the rise, which is significantly higher compared to healthy tissues ( P < 0.05 ); 48 hours after transfection, RT-qPCR analysis confirmed the transfection efficiency, and upregulation of circ-ABCB10 could significantly promote cell proliferation. Compared with the control group, silencing circ-MTCL1 could inhibit cell proliferation, overexpression of circ-ABCB10 promoted cell migration, and downregulation of circ-ABCB10 significantly inhibited cell movement ( P < 0.001 ). Upregulation of circ-ABCB10 significantly enhanced the invasiveness and motility of laryngeal cancer cells, while downregulation of circ-ABCB10 was the opposite. Compared with the KLF6 NC group, KLF6 level increased significantly in the KLF6 group, while cell viability, colony formation, scratch healing rate, invasive cell number, and Bcl-2 expression level decreased significantly in the KLF6 group, while apoptosis rate and Bax expression level increased significantly ( P < 0.05 ). KLF6 level in the si-circ-ABCB10+anti-KLF6 group was significantly lower than that in the si-circ-ABCB10+anti-KLF6-NC group ( P < 0.05 ). Meanwhile, the cell activity, colony formation number, cell scratch healing rate, number of invaded cells, and Bcl-2 all indicated an upward trend, while the cell apoptosis rate and Bax expression indicated a downward trend ( P < 0.05 ). Conclusion. The expression of circ-ABCB10 in laryngeal carcinoma was significantly higher compared to that in paracancerous tissues. Silencing circ-ABCB10 could significantly inhibit the growth and proliferation of laryngeal adenocarcinoma cells, while overexpression of circ-ABCB10 could significantly promote the growth of laryngeal adenocarcinoma cells, probably by inhibiting KLF6 to enhance the proliferation of laryngeal carcinoma and inhibit apoptosis.

Background: The development of acute lung injury (ALI) into a severe stage leads to acute respiratory distress syndrome (ARDS). The morbidity and mortality of ALI and ARDS are very high. Objective: This study is aimed to explore the effect of Krüppel-like factor 6 (KLF6) on lipopolysaccharide (LPS)-induced type II alveolar epithelial cells in ALI by interacting with cysteine-rich angiogenic inducer 61 (CYR61). Material and Methods: ALI mice model and LPS-induced type II alveolar epithelial cells were conducted to simulate ALI in vivo and in vitro. The messenger RNA (mRNA) and protein expression of KLF6 in lung tissues were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Pathological changes in lung tissues were observed by hematoxylin and eosin (H&E) staining. The viability and KLF6 expression of A549 cells treated with different concentrations of LPS were detected by cell counting kit-8 (CCK-8) assay, RT-qPCR, and Western blot analysis. After indicated treatment, the viability and apoptosis of A549 cells were analyzed by CCK-8 and TUNEL assays, and the inflammation factors of A549 cells were detected by Enzyme-linked-immunosorbent serologic assay, RT-qPCR, and Western blot analysis. The combination of KLF6 and CYR61 was determined by chromatin immunoprecipitation (ChIP)-PCR and dual-luciferase reporter assay. Results: KLF6 expression was increased in lung tissues of ALI mice and LPS-induced A549 cells. Interference with KLF6 improved the viability, reduced the inflammatory damage, and promoted the apoptosis of LPS-induced A549 cells. In addition, KLF6 could bind to CYR61. Interference with KLF6 could decrease CYR61 expression in LPS-induced A549 cells. LPS also enhanced the TLR4/MYD88 signaling pathway, which was reversed by KLF6 interference. The above phenomena in LPS-induced A549 cells transfected with Si-KLF6 could be reversed by overexpression of CYR61. Conclusion: Inhibition of KLF6 promoted the viability and reduced the inflammation and apoptosis of LPS-induced A549 cells, which was reversed by CYR61.

Long non‐coding RNAs (lncRNAs) take various biological effects in clear cell renal cell carcinoma (ccRCC) mostly through sponging with microRNAs (miRNAs). lncRNA MIR4435‐2HG is found to promote tumour progression in gastric cancer, glioblastoma and hepatocellular carcinoma. However, the role of lncRNA MIR4435‐2HG in ccRCC progression remains unknown. The purpose of this research was to investigate the potential molecular mechanism of lncRNA MIR4435‐2HG regarding the regulation of ccRCC initiation and progression. In this study, we found the up‐regulation of MIR4435‐2HG in ccRCC tissues and cell lines. Functionally, overexpression of MIR4435‐2HG promoted the proliferation as well as the metastasis in ccRCC cell lines, whereas knockdown of MIR4435‐2HG inhibited the above changes. Then, bioinformatic analysis and luciferase reporter assays confirmed the negative regulation effect of MIR4435‐2HG on miR‐513a‐5p. And further investigations showed that KLF6, which collected from the intersection of databases, was the potential conjugated mRNAs of miR‐513a‐5p. Finally, the rescue experiments revealed the relation among MIR4435‐2HG and KLF6, which showed that KLF6 could reverse the promoting effect of MIR4435‐2HG on ccRCC in vitro and in vivo. Therefore, our findings provided insight into the mechanisms of MIR4435‐2HG in ccRCC and revealed an alternative target for the clinical diagnosis and treatment of ccRCC.

Hotspot p53 mutant proteins often gain novel functions in promoting tumor metastases. However, the molecular mechanisms by which mutant p53 exerts gain-of-function in cancer are not totally understood. In this study, we demonstrate that hotspot mutant p53, p53-R273H, promotes cell scattering growth and migration via inhibiting the expression of Krupple-like factor 6 (KLF6), a Zinc finger transcription factor and a documented tumor suppressor. Restoration of KLF6 increases the expression of E-cadherin downregulated by p53-R273H and inhibits p53-R273H-induced cell migration and tumor metastasis. Further, p53-R273H reduces KLF6 transcription by upregulating EGFR expression which in turn activates AKT–FOXO1 axis. Pharmacological inhibitor of AKT, MK2206, rescues KLF6 expression and suppresses p53-R273H-induced cell migration. Clinical analyses reveal that KLF6 expression is decreased in human breast cancer specimens harboring p53 mutations, and negatively correlated with EGFR expression in human breast cancer. In addition, low expression of KLF6 is associated with poor overall survival (OS) and relapse-free survival (RFS) in p53 mutated human breast cancer patients. Together, these results reveal an important role for EGFR–AKT–FOXO1–KLF6–E-cadherin axis in mutant p53-induced cell migration and tumor metastasis.

Rat Thy-1 nephritis (Thy-1N) is an experimental mesangial proliferative glomerulonephritis (MsPGN) for studying human MsPGN. Although sublytic C5b-9 complex formation on glomerular mesangial cells (GMCs) and renal MCP-1 and RANTES production in rats with Thy-1N have been proved, the role and mechanism of MCP-1 or RANTES synthesis in GMCs induced by sublytic C5b-9 are poorly elucidated. In this study, we first found the expression of transcription factor (KLF6), co-activator (KAT7) and chemokines (MCP-1 and RANTES) was all up-regulated both in renal tissue of Thy-1N rats (in vivo) and in sublytic C5b-9-induced GMCs (in vitro). Further in vitro experiments revealed that KLF6 bound to MCP-1 promoter (-297 to -123 nt) and RANTES promoter (-343 to -191 nt), leading to MCP-1 and RANTES gene transcription. Meanwhile, KAT7 also bound to the same region of MCP-1 and RANTES promoter in a KLF6-dependent manner, and KLF6 was acetylated by KAT7 at lysine residue 100, which finally promoted MCP-1 and RANTES expression. Moreover, our in vivo experiments discovered that knockdown of renal KAT7 or KLF6 gene obviously reduced MCP-1 and RANTES production, GMCs proliferation, ECM accumulation, and proteinuria secretion in Thy-1N rats. Collectively, our study indicates that sublytic C5b-9-induced MCP-1 and RANTES synthesis is associated with KAT7-mediated KLF6 acetylation and elevated KLF6 transcriptional activity, which might provide a new insight into the pathogenesis of rat Thy-1N and human MsPGN.

The Kruppel-like factor 6 (KLF6) is a member of Kruppel-like factor family, which belong to the Zinc finger family of transcription factors that mediates various cellular processes, such as proliferation, differentiation, development, and programmed cell death. Peroxisome proliferator-activated receptors (PPARs) are a family of transcription factors belonging to the nuclear receptor superfamily and they regulate numerous genes through ligand-dependent transcriptional activation and repression. In this study, we focus on the role of KLF6 gene in virus infection and the regulation of KLF6 on PPAR-δ in orange-spotted grouper (Epinephelus coioides). The ORF sequence of EcKLF6 was 846 bp, encoding a polypeptide of 282 amino acids with three conserved Zinc finger (type Cys2-His2) domain in the C-terminal region. Basing on the detection of the mRNA levels of viral genes, western blotting of MCP protein, and morphological CPEs, we found that the overexpression of EcKLF6 suppressed the replication of Singapore grouper iridovirus (SGIV), exerting its antiviral activity against fish virus. Moreover, promoter analysis was performed to investigate whether EcKLF6 was a regulator of EcPPAR-δ. The luciferase reporter assay and real time PCR results indicated a negative regulatory role of EcKLF6 on EcPPAR-δ transcription in grouper. Further experimental analysis shows that the potential EcKLF6 binding sites may locate in the EcPPAR-δ-4-M3 (+133 to +154) and EcPPAR-δ-4-M4 (+354 to +368) region of the EcPPAR-δ promoter. Electrophoretic mobile shift assays (EMSAs) verified that EcKLF6 interacted with the binding site of the EcPPAR-δ-4-M4 promoter region. In addition, we also found that KLF6 promotes inflammatory responses in GS cells. Considering that KLF6 and PPAR-δ play opposite roles in regulating inflammatory responses, we speculated the promoting effect of KLF6 on inflammatory response may be related to its negative regulation on EcPPAR-δ. In conclusion, the present study provides the first evidence of the negative regulation of EcPPAR-δ transcription by EcKLF6 and contributes to a better understanding of the transcriptional mechanisms of EcKLF6 in fish.

Macrophages are the professional phagocytes that protect the host from infection or injury. Tissue microenvironment at the site of injury and inflammation is characterized by low oxygen concentration and poor supply of nutrients. The responding macrophages have to advance against oxygen and nutrient gradients to reach the site of inflammation to perform host protection, and tissue repair functions. Thus, evolution has fashioned macrophages to orchestrate a coordinated inflammatory and hypoxic gene program to mount an effective immune response. Here, we discovered that Kruppel-like factor 6 (KLF6) governs macrophage functions by promoting inflammatory and hypoxic response gene programming. Our in vivo studies revealed that myeloid-KLF6-deficient mice were highly resistant to endotoxin-induced systemic inflammatory response syndrome symptomatology and mortality. Using complementary gain- and loss-of-function studies, we observed that KLF6 overexpression elevate and KLF6 deficiency attenuate inducible HIF1α expression in macrophages. Our integrated transcriptomics and gene set enrichment analysis studies uncovered that KLF6 deficiency attenuates broad inflammatory and glycolytic gene expression in macrophages. More importantly, overexpression of oxygen stable HIF1α reversed attenuated proinflammatory and glycolytic gene expression in KLF6-deficient macrophages. Collectively, our studies uncovered that KLF6 govern inflammatory and hypoxic response by regulating HIF1α expression in macrophage.

Background Krüppel-like factor 6 (KLF6) is a transcription factor that participate in various pathophysiological processes, but its contribution in ischemia acute kidney injury (AKI) is lacking so far. The study aimed to investigate the expression and the role of KLF6 in kidney ischemia–reperfusion (IR) injury. Method Microarray data were collected from GSE58438 and GSE52004. The rat IR model was established to evaluate the mRNA and protein expression of KLF6 and inflammatory cytokines in serum and kidney tissues. SiRNA-KLF6 was transfected with HK-2 cells, and then a cell-based hypoxia-reoxygenation (HR) model was established. Results Bioinformatics showed KLF6 mRNA in kidney tissue is up-regulated in 3 h after IR in rat kidney, which involved in cell activation, leukocyte activation, and response to hydrogen peroxide after IR. The rat IR model results showed that KLF6 expression was peaking at 6 h, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α was increased both in serum and kidney tissues, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed that KLF6 knock-down reduced the pro-inflammatory cytokines expression. Conclusion These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) KLF6 may play a role in promoting inflammation in AKI.

We aimed to uncover the role of microRNA-181 (miR-181) in the disease onset of diabetic retinopathy (DR) and its underlying mechanism.MiR-181 levels in plasma and aqueous humor samples of non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR) and healthy subjects were analyzed by microarray and quantitative real-time polymerase chain reaction (qRT-PCR). Proliferative and migrative capacities of human retinal endothelial cells (hRECs) regulated by miR-181 were assessed. The binding between miR-181 and Kruppel-like factor 6 (KLF6) was verified by dual-luciferase reporter assay.MiR-181 was upregulated in plasma and aqueous humor samples of NPDR and PDR patients. Overexpression of miR-181 stimulated hRECs to proliferate and migrate. KLF6 was the downstream gene binding miR-181, which was involved in the regulation of hRECs by miR-181.MiR-181 is upregulated in plasma and aqueous humor of DR patients. It enhances proliferative and migratory potentials of retinal endothelial cells by targeting KLF6.

Increasing evidences have confirmed that long non-coding RNA LOXL1-AS1 functions in multiple human diseases. Here, we aim to explore the function and mechanism of LOXL1-AS1 in modulating oxidized low-density lipoprotein (ox-LDL)-induced angiogenesis of endothelial cells (ECs). Presently, we found that LOXL1-AS1 and KLF6 were upregulated in ECs treated by Ox-LDL in a dose- and time-dependent manner while miR-590-5p was downregulated. Overexpression of LOXL1-AS1 aggravated Ox-LDL mediated ECs proliferation and migration, and promoted angiogenesis both

Purpose: The phenotypic transformation of human brain vascular smooth muscle cells (HBVSMC) is widely involved in the appearance and progression of intracranial aneurysms (IA). Aneurysm (IA) Circular RNA circ_FOXO3 functions pivotally in vascular diseases and tumors, but its regulatory role as well as its molecular mechanism in IA is still uncertain. This research was to explore how circ_FOXO3 works and its mechanism in vitro model of HBVSMC IA induced by H2O2. Methods: Thirty-eight patients with IA and their normal tissues were clinically collected. Examination of endothelin-1, vascular hematoma factor, circ_FOXO3, microRNA (miR)-122-5p and KLF6 and the correlation of circ_FOXO3 with clinical case information were ensured. Establishment of an in vitro IA model was through HBVSMC induced by H2O2 and transfection with circ_FOXO3, miR-122-5p and KLF6 related plasmids was to figure out their roles in cell growth. The relationship among circ_FOXO3, miR-122-5p with KLF6 was detected. Results: Up-regulated circ_FOXO3 and KLF6 and reduced miR-122-5p were in IA tissues; Circ_FOXO3 was associated with smoking history, Hunt-Hess grading and endothelial injury degree. Repressive circ_FOXO3 or KLF6 and strengthening miR-122-5p facilitated H2O2-induced proliferation and repressed HBVSMC apoptosis, while elevation of circ_FOXO3 or depressive miR-122-5p was opposite. circ_FOXO3 bound to miR-122-5p, whose target was KLF6, which participated in controlling IA by mediating the circ_FOXO3/miR-122-5p axis. Conclusion: In summary, the findings suggest that circ_FOXO3 suppresses H2O2-induced proliferation of HBVSMC but promotes apoptosis via modulation of miR-122-5p/KLF6 axis. Targeted therapy of circ_FOXO3/miR-122-5p/KLF6 axis is supposed to be a promising treatment approach for IA patients.

Septic acute kidney injury (SAKI) represents a clinical challenge with high morbidity and mortality. The current study aimed to analyze the effects and molecular mechanism of Kruppel-like factor 6 (KLF6) on SAKI. Firstly, SAKI mouse models were established by cecum ligation and puncture, while in vivo cell models were established using lipopolysaccharide (LPS). RT-qPCR assay was subsequently performed to detect the levels of KLF6 mRNA. SAKI mice and LPS-treated TCMK-1 cells were further treated with KLF6 siRNA. Afterwards, HE staining, PAS staining, Western blot assay, and ELISA were adopted to ascertain the effects of KLF6 in pyroptosis. The binding relationships between KLF6 and miR-223-3p promoter /miR-223-3p and NLRP3 were analyzed with the help of CHIP and dual-luciferase reporter assays. RT-qPCR was adopted to determine the expression patterns of miR-223-3p and NLRP3. Lastly, a rescue experiment was designed to confirm the role of miR-223-3p. It was found that KLF6 was highly expressed in SAKI, whereas knockdown of KLF6 alleviated oxidative stress (OS) and pyroptosis in SAKI mice and LPS-treated TCMK-1 cells. Mechanistic results confirmed that KLF6 inhibited miR-223-3p via binding to the miR-223-3p promoter and promoted NLRP3. On the other hand, down-regulation of miR-223-3p activated the NLRP3/Caspase-1/IL-1β pathway and aggravated OS and pyroptosis. Overall, our findings indicated that KLF6 inhibited miR-223-3p via binding to the miR-223-3p promoter and promoted NLRP3, and activated the NLRP3/Caspase-1/IL-1β pathway, thereby aggravating pyroptosis and SAKI.

Tumor-derived extracellular vesicles (EVs) promote ovarian cancer (OC) metastasis by carrying microRNAs (miRs). This study investigated the mechanism of miR-106a-5p carried by OC cell-derived EVs in OC. miR-106a-5p expression in OC tissues and cells was measured. EVs were extracted from SKOV3 cells and normal cells. The internalization of EVs in OC cells was observed. OC cells were treated with SKOV3-EVs or SKOV3-EVs overexpressing miR-106a-5p to detect the proliferation, migration, and invasion. The expression levels of miR-106a-5p, KLF6, and PTTG1 were detected and their binding relationships were identified. Combined experiments were designed to detect the effects of KLF6 and PTTG1 on OC cells. A xenograft tumor experiment was performed to verify the mechanism of EVs-miR-106a-5p and KLF6 in OC metastasis. Consequently, miR-106a-5p was enhanced in OC and correlated with OC metastasis. SKOV3-EVs promoted the proliferation, migration, and invasion of OC cells. Mechanistically, EVs carried miR-106a-5p into other OC cells, inhibited KLF6, reduced the binding of KLF6 to the PTTG1 promoter, and upregulated PTTG1 transcription. Overexpression of KLF6 or silencing of PTTG1 attenuated the promoting effect of EVs-miR-106a-5p on OC cells. EVs-miR-106a-5p facilitated OC metastasis via the KLF6/PTTG1 axis. To conclude, OC cell-derived EVs facilitated the progression and metastasis of OC via the miR-106a-5p/KLF6/PTTG1 axis.