Association between dietary fiber intake and peripheral artery disease in hypertensive patients.

BACKGROUND: At present, no studies explored whether dietary fiber intake was associated with the risk of peripheral artery disease (PAD) in hypertensive patients. This study assessed the association between dietary fiber intake and PAD in hypertensive patients. METHODS: This cross-sectional study collected the data of 4628 participants with the measurement of ankle-brachial pressure index in the National Health and Nutrition Examination Surveys database. Univariate logistic regression analysis was applied to identify variables associated with PAD as confounding factors. Univariate and multivariable logistic regression analyses were used to explore the association between dietary fiber intake and PAD in hypertensive patients. Subgroup analysis was stratified by age, cardiovascular disease, dyslipidemia, diabetes, smoking, and physical activity. RESULTS: After adjusting for confounding factors, decreased risk of PAD was observed in hypertensive patients with dietary fiber intake > 21 g [odds ratio (OR) = 0.67, 95% confidence interval (CI) 0.46-0.99]. Compared with people with dietary fiber intake ≤ 21 g, those with dietary fiber intake > 21 g were associated with decreased risk of PAD in hypertensive patients < 60 years (OR = 0.23, 95%CI 0.08-0.66). In hypertensive patients without dyslipidemia, dietary fiber intake > 21 g were associated with reduced risk of PAD (OR = 0.33, 95%CI 0.12-0.95). Decreased risk of PAD was also found in hypertensive patients without diabetes in dietary fiber intake > 21 g group (OR = 0.50, 95%CI 0.31-0.78). Dietary fiber intake > 21 g was linked with reduced risk of PAD in hypertensive patients in never smoke group (OR = 0.46, 95%CI 0.24-0.86). CONCLUSION: Higher dietary fiber intake was associated with reduced risk of PAD in hypertensive patients, suggesting the importance of increase the daily dietary quality especially fiber intake in hypertensive people.

MicroRNA-34a-5p promotes the progression of osteoarthritis secondary to developmental dysplasia of the hip by restraining SESN2-induced autophagy.

Osteoarthritis (OA), a late-stage complication of developmental dysplasia of the hip (DDH), is a key factor leading to further degeneration of joint function. Studies have shown that Sestrin2 (SESN2) is a positive regulator in protecting articular cartilage from degradation. However, the regulatory effects of SESN2 on DDH-OA and its upstream regulators remain obscure. Here, we first identified that the expression of SESN2 significantly decreased in the cartilage of DDH-OA samples, with an expression trend negatively correlated with OA severity. Using RNA sequencing, we identified that the upregulation of miR-34a-5p may be an important factor for the decrease in SESN2 expression. Further exploring the regulation mechanism of miR-34a-5p/SESN2 is of great significance for understanding the mechanism of DDH occurrence and development. Mechanistically, we showed that miR-34a-5p could significantly inhibit the expression of SESN2, thereby promoting the activity of the mTOR signaling pathway. We also found that miR-34a-5p significantly inhibited SESN2-induced autophagy, thereby suppressing the proliferation and migration of chondrocytes. We further validated that knocking down miR-34a-5p in vivo resulted in a significant increase in SESN2 expression and autophagy activity in DDH-OA cartilage. Our study suggests that miR-34a-5p is a negative regulator of DDH-OA, and may provide a new target for the prevention of DDH-OA.

Circular RNA circ-3626 promotes bone formation by modulating the miR-338-3p/Runx2 axis.

OBJECTIVE: Disorders of bone homeostasis are the key factors leading to metabolic bone disease, such as senile osteoporosis, which is characterized by age-related bone loss. Bone marrow stromal cells (BMSCs) possess high osteogenic capacity which has been regarded as a practical approach to preventing bone loss. Previous studies have shown that the osteogenic differentiation ability of BMSCs is significantly decreased in senile osteoporosis. Recently, circular RNAs (circRNAs) have been regarded as critical regulators in controlling the osteogenic differentiation of BMSCs by sponging microRNAs (miRNAs). Our study aimed to discover new and critical osteogenesis-related circRNAs that can promote bone formation in senile osteoporosis. METHODS: We detected the dysregulated circRNAs of BMSCs upon osteogenic differentiation induction and identified the critical osteogenic circRNA (circ-3626). The relationship between circ-3626 and osteoporosis was further verified in clinical bone samples and aged mice by qPCR. Moreover, circ-3626 AAV was constructed to examine the osteogenic effect of circ-3626 on bone formation via using Micro-CT, double calcein labeling, and the three-point bending tests. Bioinformatics analysis, Luciferase report gene assays, FISH, RNA pull-down, qPCR, Western Blots, and alizarin red staining assay explore the effects and mechanisms of circ-3626 on osteogenic differentiation of BMSCs. RESULTS: Circ-3626 was identified as a pivotal osteogenesis-related circRNA via RNA sequencing. The results of alizarin red staining, Western blots, and qPCR assays suggest that overexpressing circ-3626 dramatically accelerates the osteogenic capability of BMSCs. Furthermore, the bone repair capability of aging mice could be significantly improved by circ-3626 AAV treatment. Micro RNA miR-338-3p was identified as the downstream target of circ-3626. Overexpression of circ-3626 increases the expression of Runx2 by sponging miR-338-3p, thereby promoting the osteogenic differentiation of BMSCs by upregulating the expression of osteogenic genes. In addition, Western blots, and qPCR assays suggest circ-3626 AAV treatment promote the expression of Runx2 and osteogenic marker genes. CONCLUSION: Thus, we demonstrate that circ-3626 plays a pivotal role in promoting bone formation through the miR-338-3p/Runx2 axis and may provide new strategies for preventing and treating the bone loss of senile osteoporosis.

Au/SiNCA-based SERS analysis coupled with machine learning for the early-stage diagnosis of cisplatin-induced liver injury.

Cisplatin has been widely applied in the clinical treatment of various cancers, whereas liver injury induced by its hepatotoxicity is still a severe issue. Reliable identification of early-stage cisplatin-induced liver injury (CILI) can improve clinical care and help to streamline drug development. Traditional methods, however, cannot achieve enough information at the subcellular level due to the requirement of the labeling process and low sensitivity. To overcome these, we designed an Au-coated Si nanocone array (Au/SiNCA) to fabricate the microporous chip as the surface-enhanced Raman scattering (SERS) analysis platform for the early diagnosis of CILI. A CILI rat model was established, and the exosome spectra were obtained. The principal component analysis (PCA)-representation coefficient-based k-nearest centroid neighbor (RCKNCN) classification algorithm was proposed as the multivariate analysis method to build the diagnosis and staging model. The PCA-RCKNCN model has been validated to achieve a satisfactory result, with accuracy and AUC of over 97.5%, and sensitivity and specificity of over 95%, indicating that SERS combined with the PCA-RCKNCN analysis platform can be a promising tool for clinical applications.

Pterostilbene supresses inflammation-induced melanoma metastasis by impeding neutrophil elastase-mediated thrombospondin-1 degradation.

Objective: Chronic inflammation plays a fatal role in tumor metastasis. Pterostilbene (PTE) is a natural dimethylated analogue of resveratrol with anticancer and anti-inflammatory activities. This study aimed to investigate the inhibitory effect of PTE on inflammation-associated metastasis and explore the underlying mechanisms. Methods: Lipopolysaccharide (LPS)-induced lung inflammation and melanoma metastasis models were established in mice. After PTE treatment for four weeks, the organ index, histological changes, proinflammatory cytokines, and the expression and activity of neutrophil elastase (NE), a biomarker of neutrophil influx in the lungs, were analysed. Additionally, direct effects of PTE on NE-induced B16 cell migration were explored in wound healing and Transwell assays, and the expression of thrombospondin-1 (TSP-1) and epithelial-mesenchymal transition (EMT) markers were also detected. Results: PTE obviously attenuated the LPS-induced metastasis of circulatory B16 cells to lungs by reducing the number of metastatic nodules on the lung surfaces and the lung weight/body weight ratio. PTE treatment also significantly reduced LPS-activated increase levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the lungs of tumor-bearing mice. In addition, increased expression and enzyme activity of NE and decreased expression of TSP-1 were observed, and these were blocked by PTE. In vitro, PTE at concentrations without cytotoxicity also markedly suppressed NE-triggered B16 cell migration, prevented NE-induced TSP-1 proteolysis and reversed the expression of vimentin, N-cadherin and E-cadherin. Conclusion: PTE could block inflammation-enhanced tumor metastasis, and the underlying mechanism might be associated with the inhibition of NE-mediated TSP-1 degradation.

Effects and Potential Mechanism of Zhuyu Pill Against Atherosclerosis: Network Pharmacology and Experimental Validation.

Background: Atherosclerosis (AS) is an immunoinflammatory disease associated with dyslipidemia. Zhuyu Pill (ZYP) is a classic Chinese herbal compound that has been shown to exhibit anti-inflammatory and lipid-lowering effects on AS in our previous studies. However, the underlying mechanisms by which ZYP ameliorates atherosclerosis have not yet been fully investigated. In this study, network pharmacology and in vivo experiments were conducted to explore the underlying pharmacological mechanisms of ZYP on ameliorating AS. Methods: The active ingredients of ZYP were acquired from our previous study. The putative targets of ZYP relevant to AS were obtained from TCMSP, SwissTargetPrediction, STITCH, DisGeNET, and GeneCards databases. Protein-protein interactions (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted using the Cytoscape software. Furthermore, in vivo experiments were carried out for target validation in apolipoprotein E (ApoE) -/- mice. Results: Animal experiments revealed that ZYP ameliorated AS mainly through lowering blood lipids, alleviating vascular inflammation, and decreasing the levels of vascular cell adhesion molecule-1 (VCAM1), intercellular adhesion molecule-1 (ICAM1), monocyte chemotactic protein-1 (MCP-1), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α). Additionally, the results of Real-Time quantitative PCR revealed that ZYP inhibited the gene expressions of mitogen-activated protein kinase (MAPK) p38, extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor kappa-B (NF-κB) p65. The Immunohistochemistry and Western blot assays showed the inhibitory effect of ZYP on the proteins level of p38, p-p38, p65, and p-p65. Conclusion: This study has provided valuable evidence on the pharmacological mechanisms of action of ZYP in ameliorating AS that will be useful for forming the rationale of future research studying the cardio-protection and anti-inflammation effects of ZYP.

Rapid and sensitive detection of superoxide dismutase in serum of the cervical cancer by 4-aminothiophenol-functionalized bimetallic Au-Ag nanoboxs array.

Early, efficient and sensitive detection of serum markers in cervical cancer is very important for the treatment and prognosis to cervical cancer patients. In this paper, a SERS platform based on surface enhanced Raman scattering technology was proposed to quantitatively detect superoxide dismutase in serum of cervical cancer patients. Au-Ag nanoboxs array was made by oil-water interface self-assembly method as the trapping substrate. The single-layer Au-AgNBs array was verified by SERS for possessing excellent uniformity, selectivity and reproducibility. 4-aminothiophenol (4-ATP) was used as Raman signal molecule, it will be oxidized to dithiol azobenzene under the surface catalytic reaction with the condition of PH = 9 and laser irradiation. The quantitative detection of SOD could be achieved by calculating the change of characteristic peak ratio. When the concentration was from 10 U mL-1-160 U mL-1, the concentration of SOD could be accurately and quantitatively detected in human serum. The whole test was completed within 20 min and the limit of quantitation was 10 U mL-1. In addition, serum samples from the cervical cancer, the cervical intraepithelial neoplasia and healthy people were tested by the platform and the results were consistent with those of ELISA. The platform has great potential as a tool for early clinical screening of cervical cancer in the future.

Efficacy of the Dynesys Hybrid Surgery for Patients with Multi-Segmental Lumbar Spinal Stenosis.

Objective: The efficacy of hybrid (Dynesys and fusion) surgery and the traditional transforaminal lumbar interbody fusion surgery was compared in patients with multi-segmental lumbar spinal stenosis. Methods: A total of 68 patients with multi-segmental lumbar spinal stenosis subjected to surgery were recruited between January 2013 and October 2020 in the First Affiliated Hospital of Southern University of Science and Technology. The patients were divided into a hybrid group (N = 33) and a TLIF group (N = 35) by surgery. After surgery, follow-up was conducted for 12 months. Between the two groups, the following parameters were compared: general conditions, clinical symptom scores, imaging parameters, and early complications. Results: A statistically significant difference in the duration of surgery was noted between the two groups. After 12 months of follow-up, the range of motion disappeared in the TLIF group, while 63.53% was preserved in the hybrid group with statistically significant differences. A statistically significant difference was identified in the Oswestry Disability Index one week after surgery. Nonetheless, no statistically significant differences were observed at the 12-month post-surgical follow-up. Pfirrmann grade showed a 3.03% upper adjacent segment degeneration rate in the hybrid group (1/33) at 12-month follow-up and 2.86% (1/35) in the TLIF group. Notably, no early complications (screw loosening and wound infection) were identified in the two groups. Conclusion: The Dynesys hybrid surgery combined the advantages of two systems of dynamic stabilization and rigid fusion. Besides, hybrid surgery is potentially a novel approach for the treatment of multi-segmental lumbar spinal stenosis.

Circular RNA circStag1 promotes bone regeneration by interacting with HuR.

Postmenopausal osteoporosis is a common bone metabolic disorder characterized by deterioration of the bone microarchitecture, leading to an increased risk of fractures. Recently, circular RNAs (circRNAs) have been demonstrated to play pivotal roles in regulating bone metabolism. However, the underlying functions of circRNAs in bone metabolism in postmenopausal osteoporosis remain obscure. Here, we report that circStag1 is a critical osteoporosis-related circRNA that shows significantly downregulated expression in osteoporotic bone marrow mesenchymal stem cells (BMSCs) and clinical bone tissue samples from patients with osteoporosis. Overexpression of circStag1 significantly promoted the osteogenic capability of BMSCs. Mechanistically, we found that circStag1 interacts with human antigen R (HuR), an RNA-binding protein, and promotes the translocation of HuR into the cytoplasm. A high cytoplasmic level of HuR led to the activation of the Wnt signaling pathway by stabilizing and enhancing low-density lipoprotein receptor-related protein 5/6 (Lrp5/6) and ß-catenin expression, thereby stimulating the osteogenic differentiation of BMSCs. Furthermore, overexpression of circStag1 in vivo by circStag1-loaded adeno-associated virus (circStag1-AAV) promoted new bone formation, thereby preventing bone loss in ovariectomized rats. Collectively, we show that circStag1 plays a pivotal role in promoting the regeneration of bone tissue via HuR/Wnt signaling, which may provide new strategies to prevent bone metabolic disorders such as postmenopausal osteoporosis.

A dual-amplification strategy-intergated SERS biosensor for ultrasensitive hepatocellular carcinoma-related telomerase activity detection.

Telomerase has been considered as a biomarker for early diagnosis and prognosis assessment of hepatocellular carcinoma (HCC), while the highly sensitive and specific methods remain challenging. To detect telomerase, a novel surface-enhanced Raman scattering (SERS) biosensor was constructed using the dual DNA-catalyzed amplification strategy composed of strand displacement amplification (SDA) and catalytic hairpin assembly (CHA). This strategy relies on the extension reaction of telomerase primer induced by telomerase, forming long-stranded DNAs with repetitive sequence to catalyze the follow-up SDA event. Subsequently, the SDA products can trigger the CHA reaction between the SERS probes (Au-Ag nanocages (Au-AgNCs) modified with hairpin DNA1 and Raman reporters) and capture substrate (Au@SiO2 array labeled with hairpin DNA2), resulting in the formation of numerous "hot spots" to significantly enhance the SERS signal. Results are promising that the established biosensor presented excellent reproducibility, specificity and sensitivity. Moreover, ELISA was applied as the golden standard to verify the application of the proposed biosensor in real samples and the results confirmed the satisfactory accuracy of our method. Therefore, the proposed SERS biosensor has the potential to be an ideal tool for the early screening of HCC.

LncRNA PTPRG-AS1 Promotes the Metastasis of Hepatocellular Carcinoma by Enhancing YWHAG.

OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. LncRNA PTPRG-AS1 (PTPRG-AS1) has been confirmed to function as a regulator in various cancers, whose function during HCC tumorigenesis is still not clear now. Thus, we aim to dig out the biological function and its mechanisms of PTPRG-AS1 in HCC. METHODS: PTPRG-AS1 relative expression in tissues and cells was detected and analyzed using real-time quantitative PCR (qRT-PCR). Subcellular distribution of PTPRG-AS1 was examined by FISH experiments. The effects of PTPRG-AS1 in the growth of HCC were studied by in vitro CCK-8 experiments, transwell invasion experiments, and in vivo xenograft tumor experiments. Dual-Luciferase reporter assay was performed to verify the interaction between PTPRG-AS1 and miR-199a-3p or miR-199a-3p and its target gene, YWHAG. RESULTS: PTPRG-AS1 was upregulated in HCC tissues compared with adjacent normal tissues. We identified PTPRG-AS1 mainly localized in the cytoplasm of HCC cells. Downregulation of PTPRG-AS1 suppressed HCC progression, while overexpression of PTPRG-AS1 showed the opposite effects. Furthermore, PTPRG-AS1 served as a miR-199a-3p sponge and positively regulated YWHAG expression. Besides, PTPRG-AS1 could promote HCC through miR-199a-3p/YWHAG axis. CONCLUSIONS: Taken together, we demonstrated PTPRG-AS1 may serve as a ceRNA and reversely regulates the expression of miR-199a-3p, thus facilitating HCC tumorigenesis and metastasis, which is expected to provide new clues for the treatment of HCC.

PiRNA-63049 inhibits bone formation through Wnt/ß-catenin signaling pathway.

Bone remodeling is a dynamic process between bone formation mediated by osteoblasts and bone resorption mediated by osteoclasts. Disrupted bone remodeling is a key factor in postmenopausal osteoporosis, a metabolic disorder characterized by deteriorated bone microarchitecture and increased risk of fracture. Recent studies have shown that piwi-binding RNA (piRNA) is involved in the pathogenesis of certain diseases at the post-transcriptional level. Here, we analyzed piRNA-63049 (piR-63049), which may play an essential role in bone remodeling. The expression of piR-63049 significantly increased in both bone tissues and plasma of osteoporotic rats and postmenopausal osteoporotic patients. Overexpressing piR-63049 could inhibit the osteoblastogenesis of bone marrow stromal cells (BMSCs) while knocking down piR-63049 could promote the osteoblastogenesis of BMSCs through the Wnt2b/ß-catenin signaling pathway. Moreover, knocking-down piR-63049 (piR-63049-antagonist) in vivo could attenuate the bone loss in ovariectomized rats by promoting bone formation. Taken together, the current study shows that piR-63049 inhibits bone formation through the Wnt2b/ß-catenin signaling pathway. This novel piRNA may be a potential target to increase bone formation in bone loss disorders such as postmenopausal osteoporosis.

Use of bioinformatic database analysis and specimen verification to identify novel biomarkers predicting gastric cancer metastasis.

Background: Gastric cancer (GC) is a common gastrointestinal tumor, and its metastasis has led to a significant increase in the death rate. The mechanisms of GC metastasis remain unclear. Methods: The differentially expressed genes (DmRs) and lncRNAs (DlncRs) of GC were selected from The Cancer Genome Atlas (TCGA) database. We applied the weighted gene co-expression network analysis (WGCNA) to construct co-expression modules related with GC metastasis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) method analyzed the functional regions and signal pathways of genes in vital modules. DmRs-DlncRs co-expression network were drawn for finding out hub nodes. Survival analyses of significant biomarkers were analyzed by Kaplan-Meier (KM) method. Finally, the expressions of selected biomarkers were validated in cell lines and caner tissues by quantitative real-time PCR (qRT-PCR), in GC tissue microarray by Fluorescence in situ hybridization (FISH). Results: 4776 DmRs and 213 DlncRs were involved the construction of WGCNA network, and MEyellow module was identified to have more significant correlation with GC metastasis. DmRs and DlncRs of MEyellow module were proved to be involved in the processes of cancer pathogenesis by GO and KEGG pathway analysis. Through the DmRs-DlncRs co-expression network, 7 DmRs and 1 DlncRs were considered as hub nodes. Besides, the high expression of TIMD4, CETP, KRT27, PTGDS, FAM30A was worse than low expression in GC patients survival, respectively; However, LRRC26 was opposite trend. FAM30A and TIMD4 were all significant biomarkers of GC survival and hub genes. Simultaneously, TIMD4, CETP, KRT27, PTGDS, FAM30A were increased in GC cell lines and tissues compared with GES-1 and normal tissues, respectively; the expression of LRRC26 was reduced in GC cell lines and tissues. Conclusion: This study identified 6 genes as new biomarkers affecting the metastasis of GC. Especially, FAM30A and TIMD4 might be an effective marker for predicting the prognosis and a potential-therapeutic target in GC.

CXCR4 is a prognostic marker that inhibits the invasion and migration of gastric cancer by regulating VEGF expression.

Metastasis is the main cause of poor prognosis of patients with gastric cancer (GC). Thus, current research is focused on identifying biomarkers that can predict the prognosis of patients with GC. C-X-C motif chemokine receptor 4 (CXCR4) and vascular endothelial growth factor (VEGF) have been reported to play important roles in different types of malignancies; however, their role in the prognosis of GC remains unknown. The present study aimed to investigate the potential role of CXCR4 and VEGF in predicting the prognosis of patients with GC. Immunohistochemistry analysis was performed to analyze the expression levels of CXCR4 and VEGF in a GC tissue microarray containing GC tissues and adjacent normal tissues. The association between CXCR4 or VEGF expression levels and the clinicopathological characteristics or survival outcomes were assessed. Furthermore, Transwell and wound healing assays were performed to determine the cell invasive and migratory abilities in vitro. The results demonstrated that CXCR4 promoted AGS cell invasion and migration by regulating VEGF expression. In addition, CXCR4 and VEGF expression levels were significantly upregulated in GC tissues compared with adjacent normal tissues, which was associated with a poorer overall survival (OS). Cox regression analysis demonstrated that both upregulated CXCR4 and VEGF expression were independent negative biomarkers of OS. To the best of our knowledge, the present study was the first to discover that CXCR4 and VEGF exert synergistic roles as efficient prognostic indicators for patients with GC.

Promising diagnostic and therapeutic circRNAs for skeletal and chondral disorders.

Circular RNAs (circRNAs) belong to a highly conserved subtype of non-coding RNAs, produced by the back-splicing of specific regions of pre-mRNA. CircRNAs have wide-ranging effects on eukaryotic physiology and pathology by acting as transcription regulators, miRNA sponges, protein sponges, and templates for translation. Skeletal and chondral disorders are the leading causes of pain and disability, especially for elders, affecting hundreds of millions of people worldwide. Plenty of evidence have shown that circRNAs are dysregulated and play vital roles in the occurrence and progression of skeletal and chondral disorders. Herein, we systematically summarize the emerging roles and underlying molecular mechanisms of hub circRNAs in the pathogenesis of several representative skeletal and chondral disorders. Our findings may provide further insight into the mechanistic details of the role of circRNA in bone or cartilage metabolism, and highlight the promising application of circRNAs in serving as potential diagnostic or therapeutic targets for the prevention and treatment of skeletal and chondral disorders.

COE Inhibits Vasculogenic Mimicry by Targeting EphA2 in Hepatocellular Carcinoma, a Research Based on Proteomics Analysis.

New strategies and drugs are urgently needed to improve the treatment of hepatocellular carcinoma (HCC). Vasculogenic mimicry (VM) has been elucidated being associated with the progression of HCC and anti-VM could be a promising strategy. Celastrus orbiculatu s extract (COE), a mixture of 26 compounds isolated from the Chinese Herb Celastrus Orbiculatus Vine, has been elucidated to be able to disrupt VM formation in HCC. This study aims to dissect and identify the potential targets of COE on anti-VM formation both in vitro and in vivo that are distinct from our previous study. Proteomics analysis was used to identify differential proteins in HCC cells treated with or without COE (Data are available via ProteomeXchange with identifier PXD022203). Cells invasion was examined using Transwell. Matrigel was used to establish a 3-D culture condition for VM formation in vitro. RT-PCR and Western Blot were used to examine changes of mRNA and protein respectively. Clinical resected samples were applied to confirm association between VM formation and identified targets. Subcutaneous xenograft tumor model was established to observe tumor growth and VM formation in vivo. PAS-CD34 dual staining was used to detect VM in vivo. A total of 194 proteins were identified to be differentially expressed in HCC cells treated with or without COE. In the 93 down-regulated proteins EphA2 stood out to be regulated on both RNA and protein level. Disruption EphA2 using COE or NVP inhibited VM formation and decreased VM associated biomarkers. In xenograft mouse model, COE inhibited tumor growth and VM formation via down-regulating EphA2. Taken together, our results indicate that COE could be used in HCC treatment because of its promising anti-VM effect.

Corrigendum: COE Inhibits Vasculogenic Mimicry by Targeting EphA2 in Hepatocellular Carcinoma, a Research Based on Proteomics Analysis.

[This corrects the article DOI: 10.3389/fphar.2021.619732.].

Long non-coding RNA SNHG9 inhibits ovarian cancer progression by sponging microRNA-214-5p.

Ovarian cancer ranks 7th among the most common cancer types affecting women worldwide. A number of studies have confirmed that multiple long non-coding RNAs participate in the occurrence and progression of ovarian cancer. Small nucleolar RNA host gene 9 (SNHG9) serves a role in the progression of glioblastoma and pancreatic cancer. However, the specific biological function of SNHG9 in ovarian cancer has not yet been fully investigated. The present study aimed to determine the biological role and potential molecular mechanism underlying the influence of SNHG9 in ovarian cancer. SNHG9 expression in ovarian cancer cell lines and tissues were measured via reverse transcription-quantitative PCR analysis, and cell proliferation was detected via Cell Counting Kit-8 and colony formation assays. Flow cytometry was performed to assess cell cycle progression, and Transwell and wound healing assays were performed to assess cell invasion and migration abilities. Bioinformatics software was utilized to determine the target genes of SNHG9, which were subsequently verified via dual-luciferase reporter and RNA immunoprecipitation assays. The results demonstrated that SNHG9 expression was remarkably lower in ovarian cancer cell lines and tissues compared with the negative controls. Cell function assays demonstrated that decreased SNHG9 expression notably induced the migration, colony formation, proliferation and invasiveness of ovarian cancer cells. Furthermore, the inhibitory effect of SNHG9 on the migration, colony formation, proliferation and invasion of ovarian cancer cells was partially reversed by miR-214-5p upregulation. Thus, taken together, the current results suggest that SNHG9 may serve as a tumor suppressor gene in ovarian cancer by regulating the miR-214-5p/cryptochrome circadian regulator 2 axis.

Circular RNA CDR1as promotes adipogenic and suppresses osteogenic differentiation of BMSCs in steroid-induced osteonecrosis of the femoral head.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a common debilitating orthopedic disease. The bone marrow mesenchymal stem cells (BMSCs) are a type of mesenchymal stem cells which play crucial roles in bone repair. The adipogenic/osteogenic differentiation disorder of BMSCs has been widely perceived contributing to SONFH. However, the regulatory mechanism of BMSCs differentiation disorder still remains unclear. Circular RNA (circRNA), a kind of stable ncRNA, plays important roles in regulating gene expression via various ways. To date, there are no studies to uncover the circRNA expression profile and screen out the key circRNAs playing crucial roles in adipogenic/osteogenic differentiation disorder of SONFH-BMSCs. In present study, we detected the circRNA expression profiles in SONFH-BMSCs for the first time. A total of 820 circRNAs were differentially expressed in SONFH-BMSCs, including 460 up- and 360 down-regulated circRNAs. Bioinformatics analysis indicates circRNA CDR1as, one up-regulated circRNA, may play crucial role in adipogenic/osteogenic differentiation disorder of SONFH-BMSCs via CDR1as-miR-7-5p-WNT5B axis. Knocking-down CDR1as resulted in increasing of osteogenic differentiation and decreasing of adipogenic differentiation of BMSCs, while over-expressing CDR1as resulted in decreasing of osteogenic differentiation and increasing of adipogenic differentiation of BMSCs. The miR-7-5p binding sites of CDR1as and WNT5B were verified by luciferase reporter gene assay. Our study may provide new insights into the molecular mechanisms of osteogenic/adipogenic differentiation disorder of SONFH-BMSCs and new biomarkers for the diagnosis and treatment of SONFH.

Circular RNA hsa_circRNA_0007334 is Predicted to Promote MMP7 and COL1A1 Expression by Functioning as a miRNA Sponge in Pancreatic Ductal Adenocarcinoma.

Pancreatic cancer remains one of the leading causes of cancer-related deaths worldwide. Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic tumor. Many circular RNAs (circRNAs) have proven to play vital roles in the physiological and pathological processes of tumorigenesis; however, their biogenesis in PDAC remains unclear. In this study, the expression profiles of circRNAs from 10 PDAC tissues and their paired adjacent nontumor tissues were analyzed through RNA sequencing analysis. An enrichment analysis was employed to predict the functions of the differentially expressed circRNAs. Sequence alignment information and mRNA microarray projects were used to predict the RNA regulatory network. The knockdown of circRNAs by small interfering RNAs followed by wound healing and western blot assays was used to confirm their functions in a PDAC cell line. A total of 278 circRNAs were identified as differentially expressed in PDAC tissue. Of these, we found that hsa_circRNA_0007334 was significantly upregulated and may serve as a competing endogenous RNA to regulate matrix metallopeptidase 7 (MMP7) and collagen type I alpha 1 chain (COL1A1) by the competitive adsorption of hsa-miR-144-3p and hsa-miR-577 to enhance the expression and functions of MMP7 and COL1A1 in PDAC. In vitro experiments confirmed these results. The present study is the first to propose two regulatory pathways in PDAC: hsa_circRNA_0007334-hsa-miR-144-3p-MMP7 and hsa_circRNA_0007334-hsa-miR-577-COL1A1.