Evaluation of retinal microcirculation by optical coherence tomography angiography in patients with primary membranous nephropathy.

BACKGROUND: Primary membranous nephropathy (PMN) patients may experience retinal microvascular changes. However, current diagnostic methods for PMN are not accurate in analyzing these modifications. In the present study, optical coherence tomography angiography (OCTA) was used for quantitative measurement of microvascular changes in the eyes of PMN patients. METHODS: A total of 26 patients with PMN and 26 healthy control (HC) were evaluated in this cross-sectional study. Optical coherence tomography (OCT) and OCTA were used to collect retinal thickness (RT) and microvascular parameters in the macula and optic disk in the superficial capillary plexus (SCP) of all subjects. Clinical data were collected from the PMN group. The OCT and OCTA data for PMN and HC group were compared, and the correlation between the OCTA and clinical data in the PMN group was determined. RESULTS: Vascular density (VD) and perfusion density (PD) in the macular area of the PMN group were significantly lower than those of the HC group, especially in the temporal quadrant. No significant difference in the foveal avascular zone (FAZ), optic disc microvascular parameters, RT, and retinal nerve fiber layer (RNFL) thickness was observed between the two groups. Correlation was noted between VD and PD in the macular area and clinical indicators, such as serum creatinine, serum urea nitrogen, 24-hour urine volume and urinary protein concentration. CONCLUSION: Microvascular alterations in PMN patients occurred before ocular symptoms. The present quantitative study proposed a measurement method for detecting early retinal vascular injury in PMN patients.

Sirt3 Protects Retinal Pigment Epithelial Cells From High Glucose-Induced Injury by Promoting Mitophagy Through the AMPK/mTOR/ULK1 Pathway.

Purpose: The regulation of mitophagy by Sirt3 has rarely been studied in ocular diseases. In the present study, we determined the effects of Sirt3 on AMPK/mTOR/ULK1 signaling pathway-mediated mitophagy in retinal pigment epithelial (RPE) cells in a high glucose environment. Methods: The mRNA expression levels of Sirt3, AMPK, mTOR, ULK1, and LC3B in RPE cells under varying glucose conditions were measured by real-time polymerase chain reaction (RT-PCR). The expressions of Sirt3, mitophagy protein, and AMPK/mTOR/ULK1 signaling pathway-related proteins were detected by Western blotting. Lentivirus (LV) transfection mediated the stable overexpression of Sirt3 in cell lines. The experimental groups were NG (5.5 mM glucose), hypertonic, HG (30 mM glucose), HG + LV-GFP, and HG + LV-Sirt3. Western blotting was performed to detect the expressions of mitophagy proteins and AMPK/mTOR/ULK1-related proteins in a high glucose environment during the overexpression of Sirt3. Reactive oxygen species (ROS) production in a high glucose environment was measured by DCFH-DA staining. Mitophagy was detected by labeling mitochondria and lysosomes with MitoTracker and LysoTracker probes, respectively. Apoptosis was detected by flow cytometry. Results: Sirt3 expression was reduced in the high glucose group, inhibiting the AMPK/mTOR/ULK1 pathway, with diminished mitophagy and increased intracellular ROS production. The overexpression of Sirt3, increased expression of p-AMPK/AMPK and p-ULK1/ULK1, and decreased expression of p-mTOR/mTOR inhibited cell apoptosis and enhanced mitophagy. Conclusions: Sirt3 protected RPE cells from high glucose-induced injury by activating the AMPK/mTOR/ULK1 signaling pathway. Translational Relevance: By identifying new targets of action, we aimed to establish effective therapeutic targets for diabetic retinopathy treatment.

The effect of blood flow restriction exercise on N-lactoylphenylalanine and appetite regulation in obese adults: a cross-design study.

Background: N-lactoylphenylalanine (Lac-Phe) is a new form of "exerkines" closely related to lactate (La), which may be able to inhibit appetite. Blood flow restriction (BFR) can lead to local tissue hypoxia and increase lactate accumulation. Therefore, this study investigated the effects of combining Moderate-intensity Continuous Exercise (MICE) with BFR on Lac-Phe and appetite regulation in obese adults. Methods: This study employed the cross-design study and recruited 14 obese adults aged 18-24 years. The participants were randomly divided into three groups and performed several tests with specific experimental conditions: (1) M group (MICE without BFR, 60%VO2max, 200 kJ); (2) B group (MICE with BFR, 60%VO2max, 200 kJ); and (3) C group (control session without exercise). Participants were given a standardized meal 60 min before exercise and a ad libitum 60 min after exercise. In addition, blood and Visual Analogue Scale (VAS) were collected before, immediately after, and 1 hour after performing the exercise. Results: No significant difference in each index was detected before exercise. After exercise, the primary differential metabolites detected in the M and B groups were xanthine, La, succinate, Lac-Phe, citrate, urocanic acid, and myristic acid. Apart from that, the major enrichment pathways include the citrate cycle, alanine, aspartate, and glutamate metabolism. The enhanced Lac-Phe and La level in the B group was higher than M and C groups. Hunger of the B group immediately after exercise substantially differed from M group. The total ghrelin, glucagon-like peptide-1 and hunger in the B group 1 hour after exercise differed substantially from M group. The results of calorie intake showed no significant difference among the indexes in each group. Conclusions: In conclusion, this cross-design study demonstrated that the combined MICE and BFR exercise reduced the appetite of obese adults by promoting the secretion of Lac-Phe and ghrelin. However, the exercise did not considerably affect the subsequent ad libitum intake.

Pangenome graph layout by Path-Guided Stochastic Gradient Descent.

Motivation: The increasing availability of complete genomes demands for models to study genomic variability within entire populations. Pangenome graphs capture the full genomic similarity and diversity between multiple genomes. In order to understand them, we need to see them. For visualization, we need a human readable graph layout: A graph embedding in low (e.g. two) dimensional depictions. Due to a pangenome graph's potential excessive size, this is a significant challenge. Results: In response, we introduce a novel graph layout algorithm: the Path-Guided Stochastic Gradient Descent (PG-SGD). PG-SGD uses the genomes, represented in the pangenome graph as paths, as an embedded positional system to sample genomic distances between pairs of nodes. This avoids the quadratic cost seen in previous versions of graph drawing by Stochastic Gradient Descent (SGD). We show that our implementation efficiently computes the low dimensional layouts of gigabase-scale pangenome graphs, unveiling their biological features. Availability: We integrated PG-SGD in ODGI which is released as free software under the MIT open source license. Source code is available at https://github.com/pangenome/odgi.

The 100 top-cited articles in uveitis from 1950 to 2022.

OBJECTIVES: This bibliometric analysis aimed to clarify research characteristics and trends in research on uveitis by analyzing the top 100 most-cited articles. METHODS: We used the Web of Science database to search articles published in English from January 1, 1950, to February 10, 2022, without other restrictions. The 100 most-cited articles related to uveitis were screened. The publication year, institution, author, journal, country, research topic, and research type of each article were analyzed. RESULTS: The citations of the top 100 articles ranged from 144 to 2292 times. The years 2004 and 2005 included the largest number of articles published, with 17 in total. Most of the papers were published in Ophthalmology (n = 19), a specialized ophthalmology journal. The top 100 articles originated from 14 countries, with the most from the USA (n = 44). Twenty research institutions and 18 authors contributed two or more articles, with the National Eye Institute (USA) (n = 10) and Robert B. Nussenblatt (n = 10) contributing the most. The types of studies were mainly clinical studies (n = 64), focusing on the treatment of uveitis (n = 36). CONCLUSION: This study summarizes and analyzes the research characteristics and trends of uveitis. The contribution of the USA is explained, the past and current treatments of uveitis are emphasized, and the directions of future research are clarified.

The Top 100 Most Cited Manuscripts in Retinopathy of Prematurity: A Bibliometric Analysis.

PURPOSE: To systematically summarize the research trends and emphases of ROP in the past decades by analyzing the characteristics of the top 100 cited ROP articles. METHODS: The 100 most cited articles on ROP published from January 1, 1950 to December 31, 2021 were searched by Web of Science. Information such as year of publication, number of citations, journal and impact factor, type of research and topic, country of origin, institution and authorship of each article was extracted to analyze its characteristics. RESULTS: A total of 15,928 articles were returned. These articles were published in 43 journals between 1952 and 2018, originating from 14 countries. The most widely published journal was Pediatrics (n = 19, IF = 8.109), followed by Archives of Ophthalmology (n = 15, IF = 4.399). The most cited paper (Gole et al. Archives of Ophthalmology 2005 Jul, 1614 citations) reported on the international classification of ROP. The most prevalent topic was the pathophysiology of ROP (n = 39), followed by the treatment of ROP (n = 32). Most were original research (n = 72), mainly based on research design of basic science. The most published articles were published in the United States (n = 61), and the institutions were Oregon Health & Science University, Dept Ophthalmol (n = 7). CONCLUSIONS: These 100 most frequently cited papers reflect the significant progress and several hot topics of ROP in recent decades, and this paper will help us further understand the knowledge and progress of ROP diagnosis and treatment.

Electronic health records in nursing from 2000 to 2020: A bibliometric analysis.

Background: Electronic health records (EHR) is the longitudinal data generated by patients in medical institutions and recorded by electronic medical information systems in the form of digital, which is also the most widespread application of big data in medicine. The purpose of this study was to explore the application of electronic health records in the field of nursing and determine the current research status and hotspots. Methods: A bibliometric analysis of electronic health records in nursing was undertaken from 2000 to 2020. The literature comes from Web of Science Core Collection database. We used CiteSpace (version 5.7 R5; Drexel University), which is a Java-based software that especially visualized collaborative networks and research topics. Results: A total of 2616 publications were included in the study. We found that publications increased year by year. The Journal of American Medical Informatics Association (n = 921) is the most cited. The United States (n = 1,738) has the most publications in this field. University Penn (n = 63) is the institution with the most publications. There is no influential cooperation network among the authors, of which Bates, David W (n = 12) have the largest number of publications. The relevant publications also focus on the fields of health care science and services, and medical informatics. In keywords, EHR, long-term care, mobile application, inpatient falls, and advance care planning has been researching hotspots in recent years. Conclusion: With the popularization of information systems, the publications of EHR in the nursing field have increased year by year. This study provides the basic structure, potential cooperation, and research trends of EHR in the field of nursing from 2000 to 2020, and provides a reference for nurses to effectively use EHR to help clinical work or scientific researchers explore the potential significances of EHR.

Inflammation in the peripheral blood system of Crohn's Disease.

Crohn's disease (CD) is an inflammatory bowel disease that is characterized by chronic inflammation of digestive system and has a nickname "green cancer" because of its sustained alternation of periods of flares and remissions. Here, we investigated the inflammation changes in peripheral blood system of CD patients, which are less reported in China. Peripheral blood samples of 167 CD patients and 30 healthy people, as well as their clinical information, were collected at the Second Affiliated Hospital of Soochow University. Flow cytometry was performed to analyze the ratio of CD4 T cells to CD8 T cells. Cytometric Bead Array kit was used to detect the cytokines in peripheral blood in CD patients. Moreover, the expression of inflammasomes was also detected by RT-PCR. The percentage and cell number of lymphocytes in CD patients' peripheral blood system decreased significantly, while monocytes increased remarkably. Interestingly, there was an inversion of the CD4 T cells/CD8 T cells ratio in peripheral blood of CD patients. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) increased significantly in CD patients' peripheral blood, and lipopolysaccharide (LPS) stimulation aggravate inflammatory response. In addition, the expression of nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 1 (NLRP1) and NLRP3 in peripheral blood mononuclear cells (PBMC) of CD patients increased significantly after LPS stimulation. The inflammation in peripheral blood of CD patients had significant changes, including PBMC, cytokines and inflammasomes. These results are helpful to get a deeper understanding of CD and improve the efficiency of diagnosis and treatment in China.

Remodelling of tumour microenvironment by microwave ablation potentiates immunotherapy of AXL-specific CAR T cells against non-small cell lung cancer.

The complex immunosuppressive tumour microenvironment (TME) and lack of tumour-specific targets hinder the application of chimeric antigen receptor (CAR) T cells in the treatment of solid tumours. Combining local treatment with CAR T cell immunotherapy may regulate the TME and enhance the killing potency of CAR T cells in solid tumours. Here, we show that AXL, which is highly expressed in non-small cell lung cancer (NSCLC) but not in normal tissues, might be a target for CAR T cell therapy. AXL-CAR T cells alone cause moderate tumour regression in subcutaneous and pulmonary metastatic lung cancer cell-derived xenograft models. Combination of microwave ablation (MWA) and AXL-CAR T cells have superior antitumour efficacy. MWA enhances the activation, infiltration, persistence and tumour suppressive properties of AXL-CAR T cells in AXL-positive NSCLC patient-derived xenograft tumours via TME remodelling. The combination therapy increases the mitochondrial oxidative metabolism of tumour-infiltrating CAR T cells. Combination treatment induces significant tumour suppression without observed toxicities in humanized immunocompetent mice. The synergistic therapeutic effect of MWA and AXL-CAR T cells may be valuable for NSCLC treatment.

Quantitative vessel density analysis of macular and peripapillary areas by optical coherence tomography angiography in adults with primary nephrotic syndrome.

PURPOSE: To compare the microvascular parameters of macular and peripapillary areas in adults with primary nephrotic syndrome (PNS) and healthy controls (HCs). METHODS: In this cross-sectional study, optical coherence tomography angiography (OCTA) was used to evaluate the changes in retinal microvascular in 37 adult patients with PNS and 30 HCs in this study. All subjects underwent OCTA for measuring vascular density (VD), perfusion density (PD), and foveal avascular zone (FAZ) in the superficial capillary plexus (SCP) and optical coherence tomography (OCT) for measuring central macular thickness (CMT) and retinal nerve fiber layer (RNFL) thickness. The following clinical data of the PNS group were collected: hemoglobin, platelet, total protein, albumin, prealbumin, creatinine, urea nitrogen, glomerular filtration rate, blood lipid, urinary protein, urine microalbumin, urine microalbumin/creatinine, 24-h urine volume, and 24-h urine protein quantification. The OCTA data were compared between patients with PNS and HCs, and the correlation between the OCTA data and clinical data was analyzed in the PNS group. RESULTS: VD and PD in the macular area of the PNS group were significantly lower than those in the HC group (VD: 17.025 ± 2.229 vs. 18.290 ± 0.721, P = 0.001; PD: 0.417 ± 0.058 vs. 0.450 ± 0.019, P = 0.003). No significant differences in the FAZ area and perioptic disc microvascular parameters were observed between the two groups, and patients in the PNS group showed consistent changes in the left and right eyes. VD and PD in the central macular area were positively correlated with plasma prealbumin level (VD: ρ = 0.541, P = 0.001; PD: ρ = 0.562, P < 0.001) and negatively correlated with urinary protein level (VD: ρ = -0.579, P < 0.001; PD: ρ = -0.596, P < 0.001). CONCLUSIONS: In adult patients with PNS, the decrease in VD and PD was mainly occurred in the macular area. Partly vascular density of the macular area was positively correlated with plasma prealbumin level and negatively correlated with urinary protein level. OCTA provides a convenient, non-invasive and effective method for evaluating and monitoring retinal microcirculation damage in patients with PNS.

Extracellular vesicles derived from human umbilical cord mesenchymal stem cells relieves diabetic retinopathy through a microRNA-30c-5p-dependent mechanism.

AIMS: Extracellular vesicle (EV)-transferred microRNAs (miRNAs) are proved to be potentially therapeutic candidates. Here, we attempted to unveil the role of delivery of miR-30c-5p by human umbilical cord mesenchymal stem cells (hUCMSCs)-derived EVs in diabetic retinopathy (DR). METHODS: miR-30c-5p and PLCG1 expression in streptozotocin-induced diabetes mellitus (DM) rats and high glucose (HG)-treated human retinal endothelial cells (HRECs) was quantified, followed by analysis on their interaction. EVs were isolated from hUCMSCs and co-cultured with HRECs. Through gain- and loss-of-function assays, the role of hUCMSCs-derived EV containing miR-30c-5p in DR involving PLCG1 and NF-κB pathway was analyzed in vitro and in vivo. RESULTS: Elevated PLCG1 was found in DM rats and HG-treated HRECs where miR-30c-5p was reduced while increased in hUCMSC-derived EVs. PLCG1 was pinpointed as a target gene of miR-30c-5p, which consequently disrupted the PKC/NF-κB pathway. hUCMSC-derived EVs decreased inflammation reaction by transferring miR-30c-5p in DM rats and HG-treated HRECs. Furthermore, similar changing tendency was observed in HG-treated HRECs induced by overexpressed miR-30c-5p through downregulation of PLCG1 in vivo. CONCLUSION: Overall, our findings underlined delivery of miR-30c-5p by hUCMSC-derived EVs as a novel suppressor in the inflammatory response following DR.

Effect of Sirt3 on retinal pigment epithelial cells in high glucose through Foxo3a/ PINK1-Parkin pathway mediated mitophagy.

Sirt3 is closely associated with mitophagy. This study aimed to investigate the effect and potential mechanism of Sirt3 on mitophagy in retinal pigment epithelium (RPE) in a high glucose environment. The expression levels of Sirt3, Foxo3a, PINK1, Parkin and LC3B in RPE subjected to high-glucose (HG, 30 mM D-glucose) conditions were detected by RT-PCR and western blotting. Dichloro-dihydro-fluorescein diacetate (DCFH-DA) staining was used to detect the level of reactive oxygen species (ROS) in RPE treated with HG. MitoTracker and LysoTracker probes were used to label mitochondria and lysosomes, respectively, to observe the occurrence of autophagy. Sirt3-dependent regulation of mitophagy through the Foxo3a/PINK1-Parkin pathway was further investigated by virus transfection-mediated Sirt3 overexpression and PINK1 silencing. The effect of Sirt3 overexpression on apoptosis was detected by flow cytometry. The Sirt3 expression was decreased, the Foxo3a/PINK1-Parkin pathway was inhibited, intracellular ROS level was increased, and mitophagy was attenuated in RPE under HG condition. Sirt3 overexpression activated the Foxo3a/PINK1-Parkin signaling pathway and mitophagy, and inhibited cell apoptosis. Silencing PINK1 inhibited the effect of Sirt3 overexpression on mitophagy. In summary, Sirt3 can activate mitophagy through the Foxo3a/PINK1-Parkin pathway and reduce HG-induced apoptosis of RPE. This study provides a new direction to understand the pathogenesis and develop a potential therapeutic target for diabetic retinopathy.

DRAIC promotes growth of breast cancer by sponging miR-432-5p to upregulate SLBP.

Mounting evidence suggests that lncRNAs can exert functions in cancer progression in multiple manners. In recent years, competing endogenous RNA (ceRNA) has been widely reported in human cancers as a lncRNA-dominant molecular pathway. The current study aimed at proving the role of lncRNA downregulated RNA in cancer (DRAIC) in breast cancer (BRCA) progression. To be specific, qRT-PCR assay was conducted to measure the expression of DRAIC and other downstream target genes. It was uncovered that DRAIC was expressed at a high level in BRCA cells. Functional analyses, including CCK-8, colony formation, and EdU assays demonstrated that DRAIC depletion suppressed BRCA cell proliferation. In addition, cell apoptosis was promoted due to DRAIC knockdown. The inhibitory effect of DRAIC reduction on BRCA cell migration and invasion was proven by transwell assays. Mechanistically, DRAIC was confirmed to predominantly distribute in the cytoplasm and could interact with miR-432-5p. In addition, stem-loop binding protein (SLBP) was verified to be a downstream target of miR-432-5p and was positively regulated by DRAIC. Taken together, DRAIC sponged miR-432-5p to enhance SLBP expression, by which malignant behaviors of BRCA cells were promoted. Our findings may help to provide a promising therapeutic target for BRCA patients.

The 100 top-cited articles in macular edema from 1950 to 2020.

OBJECTIVES: Systematically summarize the trend of research and the orientation of macular edema in recent decades by analyzing the characteristics of the 100 top-ranked articles. METHODS: The 100 most cited papers on macular edema published from January 1, 1950, to August 27, 2020, were reviewed by Web of Science (including the Scientific Citation Index). The each article is analyzed by extracting information such as the publication date, journal, author, country of origin, institution, number of citations, research topics, and research design types. RESULTS: Among the 100 articles, the highest cited number was 1907, and the lowest cited number was 166. These articles were published in 18 journals from 1983 to 2016, as well as in 10 countries. The most published newspapers were Ophthalmology (n = 51). The countries were the USA (n = 66). Out of 100 articles, 12 institutions and 10 authors contributed over 3 articles. The emphasis of these studies was placed on clinical studies. The most prevalent design type was the randomized controlled trial (n = 42). The etiology on macular edema can be divided into diabetic (n = 68), retinal vein occlusion (n = 21), and other (n = 11), of which the most common research topic is the non-surgical treatment of macular edema (n = 65). CONCLUSION: This study analyzed the research trends and progress of macular edema in the past 70 years, emphasizing the treatment of diabetic macular edema and the contribution of USA in the study of macular edema.

LINC01234 aggravates cell growth and migration of triple-negative breast cancer by activating the Wnt pathway.

Triple-negative breast cancer (TNBC) is a common cancer with increasing incidence and mortality in female. Increasing studies have revealed that long noncoding RNAs (lncRNAs) are novel molecules regulating tumors. Long intergenic non-protein coding RNA 1234 (LINC01234) has been demonstrated to function as an oncogene in several tumors. However, the role of LINC01234 in TNBC remains unelucidated. Herein, RT-qPCR showed that LINC01234 expression was upregulated in both TNBC tissues and cell lines. Functionally, knockdown of LINC01234 suppressed proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) process, and promoted apoptosis in TNBC cells. Xenograft mouse models revealed that LINC01234 downregulation inhibited TNBC tumor growth in vivo. Furthermore, LINC01234 was transcriptionally elevated by Sp1 transcription factor (SP1) in TNBC cells. Mechanistically, LINC01234 interacted with miR-525-5p and miR-525-5p targeted MEIS2. Rescue assays manifested that MEIS2 overexpression rescued the cellular processes inhibited by silenced LINC01234. Moreover, we validated that LINC01234 regulated the activation of the Wnt pathway through modulating MEIS2 in TNBC cells. In conclusion, LINC01234 aggravated TNBC cell growth, migration, invasion and EMT by modulating the miR-525-5p/MEIS2 axis and activating the Wnt/ß-catenin signaling pathway.

AutoBridge: Coupling Coarse-Grained Floorplanning and Pipelining for High-Frequency HLS Design on Multi-Die FPGAs.

Despite an increasing adoption of high-level synthesis (HLS) for its design productivity advantages, there remains a significant gap in the achievable frequency between an HLS design and a handcrafted RTL one. A key factor that limits the timing quality of the HLS outputs is the difficulty in accurately estimating the interconnect delay at the HLS level. This problem becomes even worse when large HLS designs are implemented on the latest multi-die FPGAs. To tackle this challenge, we propose AutoBridge, an automated framework that couples a coarse-grained floorplanning step with pipelining during HLS compilation. First, our approach provides HLS with a view on the global physical layout of the design, allowing HLS to more easily identify and pipeline the long wires, especially those crossing the die boundaries. Second, by exploiting the flexibility of HLS pipelining, the floorplanner is able to distribute the design logic across multiple dies on the FPGA device without degrading clock frequency. This prevents the placer from aggressively packing the logic on a single die which often results in local routing congestion that eventually degrades timing. Since pipelining may introduce additional latency, we further present analysis and algorithms to ensure the added latency will not compromise the overall throughput. AutoBridge can be integrated into the existing CAD toolflow for Xilinx FPGAs. In our experiments with a total of 43 design configurations, we improve the average frequency from 147 MHz to 297 MHz (a 102% improvement) with no loss of throughput and a negligible change in resource utilization. Notably, in 16 experiments we make the originally unroutable designs achieve 274 MHz on average. The tool is available at https://github.com/Licheng-Guo/AutoBridge.

Circ_0000511 accelerates the proliferation, migration and invasion, and restrains the apoptosis of breast cancer cells through the miR­326/TAZ axis.

Circular RNA 0000511 (circ_0000511) has been observed to be dysregulated in breast cancer (BC). However, the functions of circ_0000511 in breast cancer remain unknown. The expression levels of circ_0000511, ribonuclease P RNA component H1, microRNA­326 (miR­326) and transcriptional co­activator with PDZ­binding motif (TAZ) were examined by reverse transcription­quantitative PCR. Colony formation and MTT assays were conducted to analyze the cellular proliferative ability. The apoptotic rate was assessed by flow cytometry. Western blot analysis was used to evaluate the expression levels of B cell leukemia/lymphoma 2 (Bcl­2), Bcl­2 associated X apoptosis regulator, cleaved caspase­3 and TAZ. Transwell assays were performed to evaluate the migration and invasion of BC cells. The target interaction between miR­326 and circ_0000511 or TAZ was confirmed by dual­luciferase reporter assay. Xenograft assay was used to identify the function of circ_0000511 in vivo. Circ_0000511 abundance was abnormally elevated in BC tissue samples and cell lines compared with in matched normal cases. Circ_0000511 interference suppressed the proliferation, migration and invasion, and induced apoptosis of BC cells. miR­326 was a direct target of circ_0000511, and circ_0000511 silencing­mediated effects in BC cells were largely reversed by the knockdown of miR­326. miR­326 directly bound to TAZ mRNA, and TAZ accumulation largely attenuated miR­326 overexpression­induced effects in BC cells. Circ_0000511 upregulated the expression levels of TAZ partly via targeting miR­326 in BC cells. Circ_0000511 silencing restrained tumor growth in vivo. Circ_0000511 accelerated the proliferation, migration and invasion, while inhibiting the apoptosis of BC cells through upregulating TAZ expression via sponging miR­326. The circ_0000511/miR­326/TAZ axis may be a novel therapeutic target for BC treatment.

STAT3-induced HLA-F-AS1 promotes cell proliferation and stemness characteristics in triple negative breast cancer cells by upregulating TRABD.

Breast cancer (BC) is one of the most common malignances and is a leading cause of cancer-related deaths in women globally. Triple negative breast cancer (TNBC) is a common subtype of BC. Emerging evidence has indicated the crucial roles of long noncoding RNAs (lncRNAs) in the tumorigenesis of TNBC. Our aim was to explore the role and regulatory mechanism of lncRNA HLA-F antisense RNA 1 (HLA-F-AS1) in TNBC cells. Cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry analysis and western blot analysis were used to measure HLA-F-AS1-mediated cellular behaviors in TNBC. Xenograft tumor assay was applied to assess biological function of HLA-F-AS1 in vivo. Luciferase reporter assay and RNA pull down assay were used to verify the binding ability between molecules. Our findings demonstrated that HLA-F-AS1 expression was significantly upregulated in TNBC tissues and cells, and high level of HLA-F-AS1 indicated the poor prognosis of patients with TNBC. HLA-F-AS1 promoted TNBC progression by facilitating cell proliferation and stemness maintenance and inhibiting cell cycle arrest at G0/G1 stage and apoptosis in vitro as well as inducing tumor growth in vivo. HLA-F-AS1. In addition, signal transducer and activator of transcription 3 (STAT3) transcriptionally induced HLA-F-AS1 upregulation in TNBC cells via interacting with HLA-F-AS1 promoter. Moreover, HLA-F-AS1 acted as the molecular sponge of microRNA 541-3p (miR-541-3p) to elevate TRABD (TraB domain containing) expression in TNBC cells. Rescue experiments confirmed that the decrease of cell proliferation and stemness characteristics under silenced HLA-F-AS1 was rescued by TRABD overexpression in TNBC cells. In conclusion, STAT3-induced HLA-F-AS1 facilitates cell proliferation and stemness characteristics in TNBC by miR-541-3p-dependent upregulation of TRABD, which might provide a potential novel direction for the treatment of TNBC.