The impact of family history of type 2 diabetes on clinical heterogeneity in idiopathic type 1 diabetes.

AIM: To investigate the impact of family history of type 2 diabetes (T2D) on the clinical phenotypes of patients with idiopathic type 1 diabetes (T1D). METHODS: In clinically diagnosed T1D cases, a total of 335 idopathic T1D patients were included in the study, after excluding autoimmune T1D using islet autoantibody testing and monogenic diabetes using a custom monogenic diabetes gene panel obtained from clinically diagnosed T1D cases. A semi-structured questionnaire was used to collect information on the presence of T2D in first-degree relatives. The demographic and metabolic markers of idiopathic T1D patients were analysed. Subgroup analysis was performed to investigate potential interactions between T2D family history and human leukocyte antigen (HLA) genotypes. RESULTS: A total of 18.2% of individuals with idiopathic T1D had a T2D family history, and these individuals were more likely to have features associated with T2D, such as older age of onset, higher body mass index at diagnosis, lower insulin dosage and better beta-cell function, as indicated by higher levels of fasting C-peptide and 2-hour postprandial C-peptide (all P < 0.05). Additionally, regardless of HLA susceptible genotypes, the impact of family history of T2D was consistently observed in idiopathic T1D patients. Multivariable analyses showed that T2D family history was negatively correlated with the risk of beta-cell function failure in idiopathic T1D patients (P < 0.05). CONCLUSIONS: Family history of T2D may be implicated in the heterogeneity of idiopathic T1D patients.

miR-373 Inhibits Glioma Cell U251 Migration and Invasion by Down-Regulating CD44 and TGFBR2.

Glioblastoma multiforme (GBM) is the most malignant glioma, unveiling the underlying mechanisms of its aggressiveness could promote the discovery of potential targets for effective treatment. MicroRNAs (miRNAs) are important participants in both development and disease, its involvement in cancers has long been recognized. In this study, we investigated the role of miRNA-373 (miR-373) in GBM cell line U251, demonstrated that although miR-373 does not affect cell growth of U251, it inhibits migration and invasion of U251. Forced expression of miR-373 down-regulates the expressions CD44 and TGFBR2, while knockdown of CD44 and TGFBR2 presents the similar phenotype as miR-373 overexpression, suggesting that CD44 and TGFBR2 are functional targets of miR-373, down-regulation of CD44 and TGFBR2 by miR-373 are partly responsible for the migration, and invasion suppressive role of miR-373 in U251.

Marital satisfaction and depressive symptoms among Chinese older couples.

BACKGROUND: Depression is one of the most prevalent mental disorders among older people. Consistent with the Marital Discord Model of Depression (MDMD), research in Western cultures has found that marital distress is one of the risk factors for depression among older adults. However, the effect of marital distress on depression among older adults has not been examined in a collectivistic society, such as China. OBJECTIVES: The purpose of this study was to examine the relationship between marital satisfaction and depressive symptoms in a sample of Chinese older adults. Considering the dyadic nature of the data, the Actor-Partner Interdependence Model was used to test for the actor and partner effects. METHODS: The study investigated 139 older couples who were recruited from communities in Beijing, the capital of China. The Lock-Wallace Marital Adjustment and the CES-D scales were administered to the participants. RESULTS: The results indicated that neither of the actor effects was significant. One of the partner effects was significant, with the husbands' marital satisfaction predicting their wives' depressive symptoms. CONCLUSIONS: The MDMD was only partially supported among older couples in China. An asymmetrical pattern of cross-spouse effects was found, suggesting that the husbands' perception of marital dissatisfaction could significantly predict their wives' depressive symptoms.

The role of extracellular vesicles in non-alcoholic steatohepatitis: Emerging mechanisms, potential therapeutics and biomarkers.

Non-alcoholic steatohepatitis (NASH), an emerging global healthcare problem, has become the leading cause of liver transplantation in recent decades. No effective therapies in the clinic have been proven due to the incomplete understanding of the pathogenesis of NASH, and further studies are expected to continue to delve into the mechanisms of NASH. Extracellular vesicles (EVs), which are small lipid membrane vesicles carrying proteins, microRNAs and other molecules, have been identified to play a vital role in cell-to-cell communication and are involved in the development and progression of various diseases. In recent years, there has been increasing interest in the role of EVs in NASH. Many studies have revealed that EVs mediate important pathological processes in NASH, and the role of EVs in NASH is distinct and variable depending on their origin cells and target cells. This review outlines the emerging mechanisms of EVs in the development of NASH and the preclinical evidence related to stem cell-derived EVs as a potential therapeutic strategy for NASH. Moreover, possible strategies involving EVs as clinical diagnostic, staging and prognostic biomarkers for NASH are summarized.

CC Chemokines in Idiopathic Pulmonary Fibrosis: Pathogenic Role and Therapeutic Potential.

Idiopathic pulmonary fibrosis (IPF), characterized by progressive worsening of dyspnea and irreversible decline in lung function, is a chronic and progressive respiratory disease with a poor prognosis. Chronic or repeated lung injury results in inflammation and an excessive injury-repairing response that drives the development of IPF. A number of studies have shown that the development and progression of IPF are associated with dysregulated expression of several chemokines and chemokine receptors, several of which have been used as predictors of IPF outcome. Chemokines of the CC family play significant roles in exacerbating IPF progression by immune cell attraction or fibroblast activation. Modulating levels of detrimental CC chemokines and interrupting the corresponding transduction axis by neutralizing antibodies or antagonists are potential treatment options for IPF. Here, we review the roles of different CC chemokines in the pathogenesis of IPF, and their potential use as biomarkers or therapeutic targets.

CCL17 drives fibroblast activation in the progression of pulmonary fibrosis by enhancing the TGF-ß/Smad signaling.

Pulmonary fibrosis (PF) is a type of fatal respiratory diseases with limited therapeutic options and poor prognosis. The chemokine CCL17 plays crucial roles in the pathogenesis of immune diseases. Bronchoalveolar lavage fluid (BALF) CCL17 levels are significantly higher in patients with idiopathic PF (IPF) than in healthy volunteers. However, the source and function of CCL17 in PF remain unclear. Here, we demonstrated that the levels of CCL17 were increased in the lungs of IPF patients and mice with bleomycin (BLM)-induced PF. In particular, CCL17 were upregulated in alveolar macrophages (AMs) and antibody blockade of CCL17 protected mice against BLM-induced fibrosis and significantly reduced fibroblast activation. Mechanistic studies revealed that CCL17 interacted with its receptor CCR4 on fibroblasts, thereby activating the TGF-ß/Smad signaling pathway to promote fibroblast activation and tissue fibrosis. Moreover, the knockdown of CCR4 by CCR4-siRNA or blockade by CCR4 antagonist C-021 was able to ameliorate PF pathology in mice. In summary, the CCL17-CCR4 axis is involved in the progression of PF, and targeting of CCL17 or CCR4 inhibits fibroblast activation and tissue fibrosis and may benefit patients with fibroproliferative lung diseases.

Type 2 Diabetes Family History as a Significant Index on the Clinical Heterogeneity Differentiation in Type 1 Diabetes.

CONTEXT: Family history of type 2 diabetes (T2D) is an important but neglected parameter; however, its role in identifying the heterogeneity and subtypes of type 1 diabetes (T1D) remains unclear. OBJECTIVE: We investigated the effect of family history of T2D on the clinical phenotype of T1D patients and evaluated its value in T1D classification. METHODS: A total of 1410 T1D patients were enrolled in this prospective study. Information on family history of T2D in first-degree relatives (FDRs) was collected by research nurses using a semi-structured questionnaire as previously described. The effect of family history of T2D on clinical characteristics was evaluated in overall and subgroups of T1D patients stratified by islet autoantibodies, onset age, and human leukocyte antigen (HLA) genotype. Cluster analysis was performed to identify family history of T2D-related subgroups. RESULTS: A total of 10% (141/1410) of patients had at least 1 FDR diagnosed with T2D. A milder phenotype associated with family history of T2D was present in overall T1D patients, including older onset age (P < .001), higher body mass index (P < .001), higher fasting and postprandial C-peptide levels (all P < .01), lower positive rates of all islet autoantibodies, and susceptible HLA genotypes (all P < .05). Clinical heterogeneity associated with family history of T2D in the T1D subgroup stratified by autoimmunity, age of onset, and HLA genotypes was consistent. Using family history of T2D as a cluster variable, T1D patients were divided into 5 clusters, and patients in the T2D family history cluster displayed a milder phenotype than others. CONCLUSION: Family history of T2D should be considered as an important indicator for precise subclassification of T1D patients based on clinical heterogeneity.

ZNF451 favors triple-negative breast cancer progression by enhancing SLUG-mediated CCL5 transcriptional expression.

Triple-negative breast cancer (TNBC) is the most aggressive subtype with limited effective therapies because of the absence of definitive targets. Here, we demonstrate that the expression of ZNF451, a poorly characterized vertebrate zinc-finger protein, is upregulated in TNBC and associated with a poor prognosis. Elevated ZNF451 expression facilitates TNBC progression by interacting with and enhancing the activity of the transcriptional activator snail family transcriptional repressor 2 (SLUG). Mechanistically, the ZNF451-SLUG complex preferentially recruits the acetyltransferase p300/CBP-associated factor (PCAF) to the CCL5 promoter, selectively facilitating CCL5 transcription by enhancing the acetylation of SLUG and local chromatin, leading to recruitment and activation of tumor-associated macrophages (TAMs). Disturbing the ZNF451-SLUG interaction using a peptide suppresses TNBC progression by reducing CCL5 expression and counteracting the migration and activation of TAMs. Collectively, our work provides mechanistic insights into the oncogene-like functions of ZNF451 and suggests that ZNF451 is a potential target for development of effective therapies against TNBC.

Integrated cohort of esophageal squamous cell cancer reveals genomic features underlying clinical characteristics.

Esophageal squamous cell cancer (ESCC) is the major pathologic type of esophageal cancer in Asian population. To systematically evaluate the mutational features underlying clinical characteristics, we establish the integrated dataset of ESCC-META that consists of 1930 ESCC genomes from 33 datasets. The data process pipelines lead to well homogeneity of this integrated cohort for further analysis. We identified 11 mutational signatures in ESCC, some of which are related to clinical features, and firstly detect the significant mutated hotspots in TGFBR2 and IRF2BPL. We screen the survival related mutational features and found some genes had different prognostic impacts between early and late stage, such as PIK3CA and NFE2L2. Based on the results, an applicable approach of mutational score is proposed and validated to predict prognosis in ESCC. As an open-sourced, quality-controlled and updating mutational landscape, the ESCC-META dataset could facilitate further genomic and translational study in this field.

An Application of ITO Analysis in Secondary Kinship Identification.

Objective: As the methods of the paternity and kinship testing have been developed, the second-degree and more distant relationships remain challenging in forensic science. Currently, the ITO method is the mainstream method to clarify the kinship between two individuals. Methods: In this study, the ITO algorithm was used to calculate the uncle-nephew index based on 55 autosomal short tandem repeats (STRs) loci that were universally used for forensic identification. 19 STRs loci in Y chromosome were used for verification of the kinship. Results: The cumulative uncle-nephew index between A and B was calculated to 0.993 by the analysis of the genotyping results of 21 STRs. When genotyping results of the other 34 STRs were added to the calculation algorithm, the cumulative uncle-nephew index between A and B was promoted to 227.928. Meanwhile, genotyping results of 17 Y-STRs loci showed that A and B shared the same Y-STRs haplotype that was in accord with the paternal inheritance law. Conclusion: The biological uncle-nephew relationship between A and B are identified by applying the statistical principles and genetic technologies.

Neoadjuvant Immunotherapy Combined with Chemotherapy for Local Advanced Non-Small-Cell Lung Cancer in a Patient with a History of Breast Cancer: A Case Report.

Durvalumab consolidation therapy is the standard treatment after concurrent chemoradiotherapy for patients with surgically unresectable stage IIIA (N2) non-small-cell lung cancer (NSCLC). Neoadjuvant therapy followed by surgery could reduce locoregional and distant recurrence and improve the survival rate for surgically resectable NSCLC. However, the value of neoadjuvant therapy in locally advanced potentially resectable NSCLC remains controversial. Herein, we report a locally advanced potentially resectable NSCLC case with a history of breast cancer who achieved a pathologic complete response (pCR) after preoperative treatment with pembrolizumab and chemotherapy. A 50-year-old woman developed squamous cell carcinoma (SCC) (left lower lobe of the lung, stage IIIA-N2) after two years of chemotherapy and anti-HER2 therapy following a diagnosis of HER2-overexpressing breast cancer. Surgical resection was attempted despite an MDT classification as unamenable to curative surgical resection. After two cycles of neoadjuvant chemotherapy combined with anti-PD1 immunotherapy, the tumor significantly shrank, then the patient underwent a left lower lobectomy. Complete resection with negative margins (R0 resection) was achieved in the patient. The patient experienced grade 1-2 adverse effects and no grade 3 or worse adverse effects occurred. Cardiotoxicity did not occur in the patient despite prior anti-HER2 treatment for breast cancer. Our case study contributes to the existing evidence on the feasibility, efficacy, and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC. Furthermore, future studies are needed to determine which patients can benefit from immunoadjuvant therapy and the duration and course of preoperative and postoperative immunotherapy.

TRAF6 Suppresses the Development of Pulmonary Fibrosis by Attenuating the Activation of Fibroblasts.

Pulmonary fibrosis (PF) has a high mortality rate, and its pathogenesis is unknown. TNF receptor-associated factor 6 (TRAF6), a signal transducer for inflammatory signaling, plays crucial roles in the pathogenesis of immune diseases. However, its function in PF remains unknown. Herein, we demonstrated that lungs from mice with bleomycin (BLM)-induced PF were characterized by decreased expression of TRAF6 in lung fibroblasts. Enhancing TRAF6 expression protected mice from BLM-induced PF coupled with a significant reduction in fibroblast differentiation. Furthermore, we demonstrated that overexpression of TRAF6 reversed the activation of myofibroblasts from PF mice by reducing the expression of Wnt3a and subsequently suppressing Wnt/ß-catenin signaling. Additionally, the abundance of Tribbles pseudokinase 3 (TRIB3), a stress sensor, was negatively correlated with the abundance of TRAF6 in lung fibroblasts. TRIB3 overexpression decreased TRAF6 abundance by reducing TRAF6 stability in lung fibroblasts during PF. Mechanistic studies revealed that TRIB3 bound to TRAF6 and accelerated basal TRAF6 ubiquitination and degradation. Collectively, our data indicate that reduced TRAF6 expression in fibroblasts is essential for the progression of PF, and therefore, genetically increasing TRAF6 expression or disrupting the TRIB3-TRAF6 interaction could be potential therapeutic strategies for fibroproliferative lung diseases in clinical settings.

Identification of CD73 as a Novel Biomarker Encompassing the Tumor Microenvironment, Prognosis, and Therapeutic Responses in Various Cancers.

CD73 is essential in promoting tumor growth by prohibiting anti-tumor immunity in many cancer types. While the mechanism remains largely unknown, our paper comprehensively confirmed the onco-immunological characteristics of CD73 in the tumor microenvironment (TME) of pan-cancer. This paper explored the expression pattern, mutational profile, prognostic value, tumor immune infiltration, and response to immunotherapy of CD73 in a continuous cohort of cancers through various computational tools. The co-expression of CD73 on cancer cells, immune cells, and stromal cells in the TME was also detected. Especially, we examined the correlation between CD73 and CD8+ (a marker of T cell), CD68+ (a marker of macrophage), and CD163+ (a marker of M2 macrophage) cells using multiplex immunofluorescence staining of tissue microarrays. CD73 expression is significantly associated with a patient's prognosis and could be a promising predictor of these cancers. High CD73 levels are strongly linked to immune infiltrations, neoantigens, and immune checkpoint expression in the TME. In particular, enrichment signaling pathway analysis demonstrated that CD73 was obviously related to activation pathways of immune cells, including T cells, macrophages, and cancer-associated fibroblasts (CAFs). Meanwhile, single-cell sequencing algorithms found that CD73 is predominantly co-expressed on cancer cells, CAFs, M2 macrophages, and T cells in several cancers. In addition, we explored the cellular communication among 14 cell types in glioblastoma (GBM) based on CD73 expression. Based on the expression of CD73 as well as macrophage and T cell markers, we predicted the methylation and enrichment pathways of these markers in pan-cancer. Furthermore, a lot of therapeutic molecules sensitive to these markers were predicted. Finally, potential anticancer inhibitors, immunotherapies, and gene therapy responses targeting CD73 were identified from a series of immunotherapy cohorts. CD73 is closely linked to clinical prognosis and immune infiltration in many cancers. Targeting CD73-dependent signaling pathways may be a promising therapeutic strategy for future tumor immunotherapy.

Mortalin is a distinct bio-marker and prognostic factor in serous ovarian carcinoma.

This study focused on mortalin expression and its relevance to the prognosis in serous ovarian carcinoma, mortalin modulated cell malignant proliferation and EMT progression via Wnt/ß-Catenin signaling pathway. In this study, data obtained from Oncomine database, Cancer Cell Line Encyclopedia (CCLE) analysis and Immunohistochemical (IHC) staining was used to assess the expression of mortalin in serous ovarian carcinoma. The prognostic value of mortalin was analyzed using Meier plotter database and Kaplan-Meier. MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay, immunofluorescence (IF) staining, and colony formation assay were used to detect cell reproductive capacity. SK-OV-3 cell motility and epithelial-mesenchymal transition (EMT) were measured by wound-healing, migration and western-blot assays. Data from Oncomine showed that mortalin was highly expressed in serous ovarian carcinomas compared with corresponding normal controls. Similar results were found in CCLE analysis and in clinical specimens. High mortalin expression was associated with high histological grade and worse overall survival (OS) rate. The results of MTT analyses, IF staining, and colony formation assay indicated that MKT-077 (1-Ethyl-2-[[3-ethyl-5-(3-methyl-2(3H)-benzothiazolylidene)-4-oxo-2-thiazolidinylidene] methyl]-pyridinium chloride) suppressed the viability of SK-OV-3 cells. Besides, mortalin suppression restrained cell EMT progression by Wnt/ß-Catenin signaling pathway. Taken together, mortalin is over-expressed in serous ovarian carcinoma. High mortalin expression could be a candidate for the prognostic indicator and a biomarker in serous ovarian carcinoma.

The prognostic value of Tiam1 correlates with its roles in epithelial-mesenchymal transition progression and angiogenesis in lung adenocarcinoma.

BACKGROUND: Tiam1 has been identified as an oncogene and acts as an activator of GTPase Rac. Tiam1 was reported to be a promoter of cancer progression in various cancer types, while in lung adenocarcinoma, its mechanism of action is poorly understood. MATERIALS AND METHODS: Immunohistochemistry staining and Western blot assay were used to determine Tiam1 expression in lung adenocarcinoma tissues, and its association with prognosis was determined by statistical analysis. We depleted Tiam1 in both A549 and H1975 cancer cell lines. Carboxyfluorescein diacetate succinimidyl ester staining and colony formation assays were used to evaluate its impact on cell proliferation ability after depletion. Transwell migration assay and wound healing assays were performed to determine its impact on migration ability of both cell lines. Western blot assay and immunofluorescence staining were used to analyze the association between Tiam1 and epithelial-mesenchymal transition (EMT) progression. Tube formation assay and vasculogenic mimicry assay were used to show the impact of Tiam1 depletion on cancer angiogenesis. RESULTS: In this study, we demonstrated that Tiam1 overexpression in lung adenocarcinoma was significantly associated with advanced tumor grade and poor prognosis. In vitro assays indicated that Tiam1 depletion significantly inhibited cell proliferation, colony formation, and migration capacities in A549 and H1975 cells. Further investigations revealed that Tiam1 plays an important role in EMT program enhancement, angiogenesis, and accelerated tumor progression. Notably, Tiam1 depletion in cancer cells strongly inhibited human umbilical vein endothelial cell angiogenesis and vasculogenic mimicry capacities of both cancer cell lines. CONCLUSION: Tiam1 overexpression is associated with lung adenocarcinoma progression and may indicate poor prognosis. Tiam1 accelerated tumor progression due to EMT and angiogenesis enhancement. Our data may provide a novel therapeutic target for lung adenocarcinoma.

Paip1 predicts poor prognosis and promotes tumor progression through AKT/GSK-3ß pathway in lung adenocarcinoma.

The expression and biological function of Paip1 remain poorly understood in most human cancers. The objective of this research is to investigate its clinical significance and roles in lung adenocarcinoma (LADC). Immunohistochemistry was used to determine Paip1 expression in 58 cases of LADC patients with strict follow-up and 60 cases of adjacent normal lung tissues. Paip1 protein was upregulated in 77.6% (45/58) LADC tissues compared with adjacent normal lung tissues. The overexpression of Paip1 was significantly correlated with histologic grade, clinical stage, and poor prognosis. Small interfering RNA-mediated transfection was performed in A549 and H1299 cells. Paip1 depletion attenuated the proliferation and migration of A549 and H1299 cells. Paip1 also changed the expression of epithelial-to-mesenchymal transition markers including E-cadherin, Vimentin, Slug, and Snail. Furthermore, Paip1 regulated AKT/GSK-3ß oncogenic signaling pathways. In conclusions, Paip1 expression is frequently upregulated in LADC, and its overexpression correlates with poor prognosis in LADC patients. Attenuated Paip1 expression suppresses proliferation and epithelial-to-mesenchymal transition-related migration of A549 and H1299 cells by regulating the AKT/GSK-3ß signaling pathway.

Paip1 overexpression is involved in the progression of gastric cancer and predicts shorter survival of diagnosed patients.

BACKGROUND: Gastric cancer (GC) is a major leading cause of cancer mortality worldwide. Polyadenylate (poly(A))-binding protein (PABP)-interacting protein 1 (Paip1) is a key regulator in the initiation of translation; however, its role in GC remains to be investigated. PURPOSE: The purpose of this study is to determine Paip1 expression levels and investigate its underlying molecular mechanism in GC. PATIENTS AND METHODS: In the present study, a total of 90 GC samples and 90 adjacent noncancerous tissues were used to examine the expression of Paip1. In order to gain a deep insight into the molecular mechanism of Paip1 in GC, the Paip1 siRNA sequences were transfected into GC cell lines (MGC-803 and SGC-7901), respectively. Meanwhile, Paip1 plasmid was used to mediate overexpression of Paip1. Cell proliferation were examined via colony formation assay, EdU assay and flow cytometry assay. Cell metastasis were discovered via wound healing assay and Transwell assays. In addition, key EMT makers were detected by Western blotting assay. RESULTS: In this study, Paip1 expression was observed to be upregulated in GC and was associated with shorter overall survival. Knockdown of Paip1 inhibited cell proliferation, migration and caused cell cycle arrest in GC cells, whereas its overexpression reversed these effects. Another mechanistic study showed that Paip1 overexpression promoted EMT progression and regulated its targets expression. CONCLUSION: High expression of Paip1 plays a significant role in the progression of GC and may be a potential biomarker of poor prognosis as well as a therapeutic target.

How Do I Narrate My Marriage: The Relationship Between Attachment Orientation and Quality of Autobiographical Memory.

Attachment orientations play important roles in the generation of emotional autobiographical memory (AM). However, little research has considered the quality of autographical narratives, which may reflect the structure and content of internal working models (IWMs) of attachment. The purpose of the current study was to investigate the relationship between attachment orientations and narrative quality of marriage-related autobiographical memories. Ninety-four married adults were asked to retrieve two episodes of emotional autobiographical memories. The coherence and vividness of their narratives were then coded. Results indicated that adults who were highly avoidant were more likely to present their memories in a less coherent way and to describe negative memories with more perceptual details. In contrast, attachment anxiety was associated with lower vividness of negative memories. The current findings suggest that an attachment schematic-processing strategy was used in narrating the attachment-related experiences.

Metastasis of esophageal small cell carcinoma to the appendix: A case report and literature review.

Primary small cell carcinoma (SCC) of the esophagus is characterized by high malignancy with a tendency to metastasize early through lymph and blood circulation. Metastasis of esophageal SCC frequently occurs to distant organs such as liver and lung. However, few cases of appendiceal metastasis have been reported. This paper first presents a pathologically confirmed case with metastasis of esophageal SCC to the appendix. This particular case highlights the importance of pathological diagnosis and provides new evidence of appendiceal metastasis from esophageal SCC.

Inhibition of miR-7 promotes angiogenesis in human umbilical vein endothelial cells by upregulating VEGF via KLF4.

Recent lentiviral-based microRNA (miRNA) library screening has identified miRNA-7 (miR-7) as an anti­angiogenic miRNA in human umbilical vein endothelial cells (HUVECs). However, the underlying mechanism of miR-7 in the suppression of angiogenesis remains largely unknown. In the present study, we report that miR-7 inhibition promoted angiogenesis by upregulating vascular endothelial growth factor (VEGF) and directly targeting Krüppel-like factor 4 (KLF4). Downregulation of miR-7 promoted tube formation of HUVECs, accompanied by upregulation of mRNA and protein levels of both VEGF and KLF4. miR-7 directly targeted KLF4 as demonstrated by luciferase reporter assay and miR-7 mimics decreased KLF4. Furthermore, bioinformatic analysis revealed the presence of multiple DNA-binding elements of KLF4 in the VEGF promoter. Chromatin immunoprecipitation (ChIP) demonstrated that the KLF4 antibody specifically pulled down the VEGF promoter in the HUVECs. Furthermore, ectopic overexpression of KLF4 induced VEGF mRNA and protein levels. In addition, KLF4 silencing inhibited the angiogenesis induced by the miR-7 inhibitor in the HUVECs. Our results demonstrated that KLF4 is a direct target of miR-7 and a transcription activator of VEGF. These findings indicate that the miR-7-KLF4-VEGF signaling axis plays an important role in the regulation of angiogenesis in HUVECs, suggesting that miR-7 is a potential agent for the development of anti-angiogenic therapeutics in vascular diseases and solid tumors.