Case report: Clinical features of pediatric acute myeloid leukemia presenting with cardiac tamponade: a case series study and literature review.

Objective: This study aims to elucidate the clinical features observed in cases of pediatric acute myeloid leukemia (AML) initially presenting with cardiac tamponade and to share treatment experiences. Materials and methods: Five pediatric patients were initially diagnosed with AML accompanied by cardiac myeloid sarcoma (MS). The diagnosis was established by examining our hospital records and reviewing pertinent literature from 1990 to July 2023, accessible through MEDLINE/PubMed. We comprehensively assessed the clinical characteristics and treatment modalities employed for these patients. Result: Five pediatric patients presented with acute symptoms, including shortness of breath, malaise, cough, and fever, leading to their hospitalization. Physical examination revealed irritability, hypoxia, tachypnea, tachycardia, and hypotension. Initial detection utilized chest X-ray or echocardiogram, leading to subsequent diagnoses based on pericardial effusion and/or bone marrow examination. Two patients received chemotherapy at the time of initial diagnosis, one with cytarabine and etoposide, and the other with cytarabine and cladribine. Post-treatment, their bone marrow achieved remission, and over a 2.5-year follow-up, their cardiac function remained favorable. Unfortunately, the remaining three patients succumbed within two weeks after diagnosis, either due to receiving alternative drugs or without undergoing chemotherapy. Conclusion: This is the first and largest case series of pediatric AML patients with cardiac MS, manifesting initially with cardiac tamponade. It highlights the rarity and high mortality associated with this condition. The critical factors for reducing mortality include identifying clinical manifestations, conducting thorough physical examinations, performing echocardiography promptly, initiating early and timely pericardial drainage, and avoiding cardiotoxic chemotherapy medications.

DLEU2/EZH2/GFI1 Axis Regulates the Proliferation and Apoptosis of Human Bone Marrow Mesenchymal Stem Cells.

Long non-coding RNAs (lncRNAs) has become a vital regulator in the pathogenesis of osteoporosis (OP). This study aimed to investigate the role of lncRNA DLEU2 in the development of proliferation and apoptosis of human bone marrow mesenchymal stem cells (hBMSCs). High-throughput sequencing in bone tissues from 3 pairs of healthy donors and OP patients was used to search for differential lncRNAs. The expression of DLEU2 was also verified in bone tissues. The hBMSCs were transfected with DLEU2 ASO. Cell viability was detected suing MTT. Cell proliferation was determined using colony formation and EdU assays. Cell cycle and apoptosis was detected using flow cytometry. RIP, RNA pulldown, and Co-IP assays were carried out to verify the interaction between protein and protein/RNA. The binding sites between GFI1 and the promoter of DLEU2 was verified using ChIP and luciferase assays. DLEU2 expression was down-regulated in OP patients. Knockdown of DLEU2 expression significantly inhibited proliferation and promoted apoptosis of hBMSCs. Moreover, DLEU2 could interact with EZH2 to induce the activation of GFI1. Additionally, GFI1 transcriptionally activated DLEU2. Taken together, DLEU2/EZH2/GFI1 axis suppressed proliferation and enhanced hBMSC apoptosis. This may provide novel strategy for OP.

A deep learning model adjusting for infant gender, age, height, and weight to determine whether the individual infant suit ultrasound examination of developmental dysplasia of the hip (DDH).

Objective: To examine the correlation between specific indicators and the quality of hip joint ultrasound images in infants and determine whether the individual infant suit ultrasound examination for developmental dysplasia of the hip (DDH). Method: We retrospectively selected infants aged 0-6 months, undergone ultrasound imaging of the left hip joint between September 2021 and March 2022 at Shenzhen Children's Hospital. Using the entropy weighting method, weights were assigned to anatomical structures. Moreover, prospective data was collected from infants aged 5-11 months. The left hip joint was imaged, scored and weighted as before. The correlation between the weighted image quality scores and individual indicators were studied, with the last weighted image quality score used as the dependent variable and the individual indicators used as independent variables. A Long-short term memory (LSTM) model was used to fit the data and evaluate its effectiveness. Finally, The randomly selected images were manually measured and compared to measurements made using artificial intelligence (AI). Results: According to the entropy weight method, the weights of each anatomical structure as follows: bony rim point 0.29, lower iliac limb point 0.41, and glenoid labrum 0.30. The final weighted score for ultrasound image quality is calculated by multiplying each score by its respective weight. Infant gender, age, height, and weight were found to be significantly correlated with the final weighted score of image quality (P < 0.05). The LSTM fitting model had a coefficient of determination (R2) of 0.95. The intra-class correlation coefficient (ICC) for the α and ß angles between manual measurement and AI measurement was 0.98 and 0.93, respectively. Conclusion: The quality of ultrasound images for infants can be influenced by the individual indicators (gender, age, height, and weight). The LSTM model showed good fitting efficiency and can help clinicians select whether the individual infant suit ultrasound examination of DDH.

LncRNA PTTG3P promotes tumorigenesis and metastasis of NSCLC by binding with ILF3 to maintain mRNA stability and form a positive feedback loop with E2F1.

Non-small cell lung cancer (NSCLC) is a highly lethal disease worldwide. We found the pseudogene-derived lncRNA PTTG3P is upregulated in NSCLC and associated with larger tumor size, advanced staging, and poor prognosis. This study investigated the oncogenic roles and mechanisms of PTTG3P in NSCLC. We demonstrate that PTTG3P promoted NSCLC cell proliferation, migration, tumorigenesis, and metastasis while inhibiting apoptosis in vitro and in vivo. Mechanistically, PTTG3P formed an RNA-protein complex with ILF3 to maintain MAP2K6 and E2F1 mRNA stability, two oncogenic factors involved in NSCLC progression. RNA-seq revealed MAP2K6 and E2F1 were downregulated upon PTTG3P knockdown. RIP and RNA stability assays showed PTTG3P/ILF3 interaction stabilized MAP2K6 and E2F1 transcripts. Interestingly, E2F1 transcriptionally upregulated PTTG3P by binding its promoter, forming a positive feedback loop. Knockdown of E2F1 or PTTG3P attenuated their mutual regulatory effects on cell growth and migration. Thus, a PTTG3P/ILF3/E2F1 axis enhances oncogene expression to promote NSCLC pathogenesis. Our study reveals PTTG3P exerts oncogenic functions in NSCLC via mRNA stabilization and a feedback loop, highlighting its potential as a prognostic biomarker and therapeutic target.

Efficacy of tolvaptan in postoperative volume therapy for acute Stanford type A aortic dissection.

BACKGROUND: Despite the increasing application of tolvaptan in cardiac surgery, there is no information on the use of tolvaptan in Stanford patients with type A aortic dissection. This study aimed to evaluate the postoperative clinical effects of tolvaptan in patients with type A aortic dissection  after tafter surgery. METHODS: A retrospective analysis was performed on 45 patients treated for type A aortic dissection in our hospital from 2018 to 2020. These included 21 patients who were treated with tolvaptan (Group T) and 24 patients who received traditional diuretics (Group L). The hospital's electronic health records were used to obtain perioperative data. RESULTS: Group T did not differ significantly from Group L in terms of the duration of mechanical ventilation, postoperative blood required, length of catecholamine use, or the amount of intravenous diuretic drugs administered (all P > 0.05). The development of postoperative atrial fibrillation was significantly less in the tolvaptan group (P = 0.023). The urine volumes and change in body weight loss were slightly higher in group T than in group L but the differences were non-significant (P > 0.05). Serum potassium, creatinine, and urea nitrogen levels did not differ between the groups in the week after surgery, At the same time, sodium was significantly higher in the Group T group on day 7 after transfer from the ICU (P = 0.001). In Group L, sodium levels were also elevated by day 7 (P = 0.001). On days 3 and 7, serum creatinine and urea nitrogen levels increased in both groups (both P < 0.05). CONCLUSIONS: Both tolvaptan and traditional diuretics were found to be effective and safe for patients with acute Stanford type A aortic dissection. Moreover, tolvaptan may be associated with reducing the incidence of postoperative atrial fibrillation.

Artificial Intelligence-Assisted Ultrasound Diagnosis on Infant Developmental Dysplasia of the Hip Under Constrained Computational Resources.

OBJECTIVES: Ultrasound (US) is important for diagnosing infant developmental dysplasia of the hip (DDH). However, the accuracy of the diagnosis depends heavily on expertise. We aimed to develop a novel automatic system (DDHnet) for accurate, fast, and robust diagnosis of DDH. METHODS: An automatic system, DDHnet, was proposed to diagnose DDH by analyzing static ultrasound images. A five-fold cross-validation experiment was conducted using a dataset containing 881 patients to verify the performance of DDHnet. In addition, a blind test was conducted on 209 patients (158 normal and 51 abnormal cases). The feasibility and performance of DDHnet were investigated by embedding it into ultrasound machines at low computational cost. RESULTS: DDHnet obtained reliable measurements and accurate diagnosis predictions. It reported an intra-class correlation coefficient (ICC) on α angle of 0.96 (95% CI: 0.93-0.97), ß angle of 0.97 (95% CI: 0.95-0.98), FHC of 0.98 (95% CI: 0.96-0.99) and PFD of 0.94 (95% CI: 0.90-0.96) in abnormal cases. DDHnet achieved a sensitivity of 90.56%, specificity of 100%, accuracy of 98.64%, positive predictive value (PPV) of 100%, and negative predictive value (NPV) of 98.44% for the diagnosis of DDH. For the measurement task on the US device, DDHnet took only 1.1 seconds to operate and complete, whereas the experienced senior expert required an average 41.4 seconds. CONCLUSIONS: The proposed DDHnet demonstrate state-of-the-art performance for all four indicators of DDH diagnosis. Fast and highly accurate DDH diagnosis is achievable through DDHnet, and is accessible under constrained computational resources.

MNX1-AS1 Promotes Phase Separation of IGF2BP1 to Drive c-Myc-Mediated Cell-Cycle Progression and Proliferation in Lung Cancer.

c-Myc and E2F1 play critical roles in many human cancers. As long noncoding RNAs (lncRNA) are known to regulate various tumorigenic processes, elucidation of mechanisms of cross-talk between lncRNAs and c-Myc/E2F1-related signaling pathways could provide important insights into cancer biology. In this study, we used integrated bioinformatic analyses and found that the lncRNA MNX1-AS1 is upregulated in non-small cell lung cancer (NSCLC) via copy-number gain and c-Myc-mediated transcriptional activation. High levels of MNX1-AS1 were associated with poor clinical outcomes in patients with lung cancer. MNX1-AS1 promoted cell proliferation and colony formation in vitro and tumor growth in vivo. MNX1-AS1 bound and drove phase separation of IGF2BP1, which increased the interaction of IGF2BP1 with the 3'-UTR (untranslated region) of c-Myc and E2F1 mRNA to promote their stability. The c-Myc/MNX1-AS1/IGF2BP1 positive feedback loop accelerated cell-cycle progression and promoted continuous proliferation of lung cancer cells. In a lung cancer patient-derived xenograft model, inhibition of MNX1-AS1 suppressed cancer cell proliferation and tumor growth. These findings offer new insights into the regulation and function of c-Myc and E2F1 signaling in NSCLC tumorigenesis and suggest that the MNX1-AS1/IGF2BP1 axis may serve as a potential biomarker and therapeutic target in NSCLC. SIGNIFICANCE: MNX1-AS1 drives phase separation of IGF2BP1 to increase c-Myc and E2F1 signaling and to activate cell-cycle progression to promote proliferation in NSCLC.

Case Report: Long-term follow-up of desert hedgehog variant caused 46, XY gonadal dysgenesis with multiple complications in a Chinese child.

Background: Desert hedgehog (DHH), as a member of the Hedgehog (HH) family, is mainly involved in testicular development and peripheral nerve sheath formation. A DHH variant has been identified in patients with 46, XY gonadal dysgenesis (46, XY GD) with or without neuropathy, but few reports mention the involvement of other complications. Case presentation: Here, we report a Chinese female patient who was hospitalized at 14.3 years old due to slow breast development for more than 1 year. She had a female genitalia phenotype and breast development started at 13 years old but progressed slowly. She was not yet menarche on admission, and she had intermittent muscle cramps in her hands and feet. Her karyotype analysis was 46, XY and the SRY gene was positive. Surgical exploration revealed no uterus or ovaries, and the pathology of bilateral gonads was dysplastic testis tissue, which was consistent with partial gonadal dysgenesis (PGD). Genetic analysis identified a homozygous pathogenic variant in DHH exon 3 (c.1027T>C, p. Cys343Arg). During the 6-year follow-up, she received estrogen replacement therapy, resulting in breast development progression without gender dysphoria. However, her peripheral neuropathy became more obvious, and a nerve conduction study (NCS) indicated decreased nerve conduction velocity and action potential. In addition, she also suffered complications such as obesity, insulin resistance, fatty liver, and gastric ulcers. Conclusion: In the present study, we reported a case of 46, XY GD with minifascicular neuropathy caused by a DHH homozygous variant, and we summarized the reported cases worldwide. For the first time in such patients, we showed a comparison of NCS changes with age as well as the presence of multiple complications not previously reported.

The short-term efficacy of adventitial inversion with graft eversion anastomosis for the reconstruction of the aortic sinus in the root treatment of aortic dissection.

Background: The surgical approaches for a mildly affected aortic sinus (AS) are varied and controversial. Here, the AS was reconstructed using the extended adventitial inversion with graft eversion anastomosis technique before its perioperative and short-term efficacy was compared with that of the vascular grafts that wrap the aortic wall and the right atrial shunt technique, providing a new basis for surgical management strategies. Method: A total of 101 patients with mildly affected AS were enrolled in the clinical trial. The extended adventitial inversion suture and the graft eversion anastomosis technique was performed in group A. Aorta wrapping and the right atrial shunt technique were performed in group B. The primary endpoints were reoperation-related events and fatal events related to the aorta, while the secondary endpoints were the duration of surgery and structural changes in the aortic root. Cardiac ultrasound and aortic computed tomography angiography examinations were performed before surgery, 2 weeks after surgery, and 1 year after surgery. Results: Compared to group B (n = 56), group A (n = 36) had a significantly shorter duration of surgery (the time from skin incision to skin closure) and a reduced time from shutdown to skin closure (P < 0.05). Cardiovascular ultrasound examinations performed at follow-up 12 months after surgery and 2 weeks after surgery revealed a significant increase in the diameter of the aortic sinotubular junction (STJ) of group B (n = 50) (P < 0.05). The extended adventitial inversion suture and the graft eversion anastomosis technique (n = 33) performed better than Aorta wrapping and the right atrial shunt technique in terms of persistence of the false lumen closure effect, anastomotic leakage, and reduction in aortic valve (P < 0.05), and there was a significant difference between the two groups in terms of the incidence of events related to reoperation (P < 0.05). Conclusion: Compared with the aorta wrapping and the right atrial shunt technique, the extended adventitial inversion suture and the graft eversion anastomosis technique allow shortening of the operation time and preventing near-term dilation of the STJ, with improved safety and an improved short-term surgical effect.

Construction of a new automatic grading system for jaw bone mineral density level based on deep learning using cone beam computed tomography.

To develop and verify an automatic classification method using artificial intelligence deep learning to determine the bone mineral density level of the implant site in oral implant surgery from radiographic data obtained from cone beam computed tomography (CBCT) images. Seventy patients with mandibular dentition defects were scanned using CBCT. These Digital Imaging and Communications in Medicine data were cut into 605 training sets, and then the data were processed with data standardization, and the Hounsfiled Unit (HU) value level was determined as follows: Type 1, 1000-2000; type 2, 700-1000; type 3, 400-700; type 4, 100-400; and type 5, - 200-100. Four trained dental implant physicians manually identified and classified the area of the jaw bone density level in the image using the software LabelMe. Then, with the assistance of the HU value generated by LabelMe, a physician with 20 years of clinical experience confirmed the labeling level. Finally, the HU mean values of various categories marked by dental implant physicians were compared to the mean values detected by the artificial intelligence model to assess the accuracy of artificial intelligence classification. After the model was trained on 605 training sets, the statistical results of the HU mean values of various categories in the dataset detected by the model were almost the same as the HU grading interval on the data annotation. This new classification provides a more detailed solution to guide surgeons to adjust the drilling rate and tool selection during preoperative decision-making and intraoperative hole preparation for oral implant surgery.

Copy number amplification and SP1-activated lncRNA MELTF-AS1 regulates tumorigenesis by driving phase separation of YBX1 to activate ANXA8 in non-small cell lung cancer.

Long non-coding RNAs (lncRNAs) are reported to play key roles in tumorigenesis. However, the mechanisms underlying lncRNA-mediated regulation of RNA-binding protein phase separation in tumorigenesis have not been completely elucidated. In this study, an oncogenic lncRNA MELTF-AS1 was identified using systematic data analysis, screening, and verification. MELTF-AS1 was markedly upregulated in non-small cell lung cancer (NSCLC). High MELTF-AS1 levels were associated with advanced tumor-node-metastasis stage (TNM), high tumor size, and decreased survival time. Functionally, MELTF-AS1 regulated cell proliferation and metastasis in vitro and in vivo. RNA sequencing analysis revealed that MELTF-AS1 knockdown specifically modulated genes associated with cell proliferation, apoptosis, and migration. Mechanistically, at the genome level, copy number amplification promoted MELTF-AS1 expression. At the transcriptional level, the transcription factor SP1 directly activated MELTF-AS1 transcription by binding to its promoter. Furthermore, MELTF-AS1 could directly bind and drive the phase separation of YBX1, which was an RNA-binding protein and involved in tumorigenesis, thus activating ANXA8 transcription and promoting tumorigenesis of NSCLC. Aberrant activation of ANXA8 and promotion of tumorigenesis have been found in a variety of tumors. These novel findings demonstrated the critical role of MELTF-AS1-driven phase separation-mediated transcriptional regulation and provided a potential novel diagnostic and therapeutic target for NSCLC.

Comparative Efficacy of Dapagliflozin and Empagliflozin of a Fixed Dose in Heart Failure: A Network Meta-Analysis.

Background: The efficacy of dapagliflozin and empagliflozin in sodium-glucose cotransport-2 inhibitors (SGLT-2i) in patients with heart failure (HF) has been discovered. However, which drug could improve varied prognostic outcomes has not been elucidated. Hence, we compared their efficacies on the prognostic improvement of HF. Methods: Databases including PubMed, EMBASE, Scopus, Google Scholars, and the Cochrane Library were searched for all related randomized controlled trials (RCTs) published from inception to 13 October 2021. Network meta-analyses were performed to generate matrices to show the effect size for pairwise comparison regarding all the interventions. Results: Eventually a total of 11 RCTs were included in this study. For the primary endpoints, dapagliflozin was comparable with empagliflozin in hospitalization for HF, and empagliflozin (OR=0.70, 95%CI: 0.59-0.84) decreased the risk of exacerbation of HF over dapagliflozin. For the secondary endpoints, dapagliflozin was comparable with empagliflozin in cardiovascular (CV) death /hospitalization for HF, and for CV death, dapagliflozin (OR=0.78, 95%CI: 0.65-0.92) significantly reduced mortality over the placebo. For the tertiary endpoints, dapagliflozin (OR=0.80, 95%CI: 0.66-0.98) significantly decreased the mortality over empagliflozin in all-cause death, and neither drug significantly increased the risk of hypoglycemia. Recommendations: Overall, 10 mg/day dapagliflozin may be the optimal recommendation for its premium and comprehensive effect on improving the prognosis of patients with HF compared to 10 mg/day empagliflozin.

EZH2-mediated epigenetic suppression of lncRNA PCAT18 predicts a poor prognosis and regulates the expression of p16 by interacting with miR-570a-3p in gastric cancer.

It was recently demonstrated that long noncoding RNAs (lncRNAs) have key regulation functions in the biology of human cancer. The current study aimed to determine the expression, clinicopathological characteristics and functional roles of lncRNA PCAT18 in gastric cancer (GC). By analysis of (Gene Expression Omnibus) GEO and TCGA data, following experimental verification, we identified the function role and molecular mechanism of PCAT18 in tumorigenesis of GC. We discovered that PCAT18 is significantly decreased in paired GC tissues and correlates with a poor outcome. Mechanistic studies found that suppression of the expression of EZH2 could prevent its binding to the PCAT18's promoter region and decrease H3K27's trimethylation modification. In addition, PCAT18 could adjust cell proliferation of GC in vitro as well as in vivo. Further mechanism research revealed that PCAT18 could regulate the expression of p16 by interacting with miR-570a-3p, thus inhibiting cell proliferation of GC. Our results have shown that the histone modification-mediated epigenetic suppression of PCAT18 and its essential role of PCAT18 in GC oncogenesis, which could provide a theoretical basis for GC therapy.

CircETFA upregulates CCL5 by sponging miR-612 and recruiting EIF4A3 to promote hepatocellular carcinoma.

As a kind of malignant tumors, hepatocellular carcinoma (HCC) has been studied continuously, but the mechanisms are not well understood. Circular RNAs (circRNAs) are widespread in eukaryotes and play an important role in the growth of organisms and in the occurrence of diseases. The role of circRNAs in HCC remains to be further explored. In this study, CircRNA microarray analysis was used to assess the plasma from HCC patients and healthy controls and to identify circRNAs involved in HCC tumorigenesis. CircETFA was overexpressed in HCC tissues, plasma, and cells. Clinicopathological data revealed that abnormally high circETFA expression was associated with a poor prognosis. In function, circETFA promotes the malignant phenotype of HCC cells in vivo and in vitro, inhibits cycle arrest, and decreases the proportion of apoptotic cells. In mechanism, it can upregulate C-C motif chemokine ligand 5 (CCL5) in HCC cells, thereby regulating the phosphoinositide 3-kinase (PI3K)/Akt pathway and other key downstream effectors (e.g., FoxO6). Furthermore, circETFA prolonged the half-life of CCL5 mRNA by recruiting the eukaryotic initiation factor 4A3 (EIF4A3) and acted as a sponge of hsa-miR-612 to suppress the silencing effect of hsa-miR-612 on CCL5. In conclusion, CircETFA can increase the expression of CCL5 to promote the progression of HCC by sponging hsa-mir-612 and recruiting EIF4A3, and is promising as a novel biomarker and therapeutic target.

ELF3-AS1 contributes to gastric cancer progression by binding to hnRNPK and induces thrombocytosis in peripheral blood.

Numerous studies have reported that a variety of long noncoding RNAs (lncRNAs) can promote the proliferation, invasion, and migration of different tumor cells. However, different lncRNAs regulate cell functions in various forms, and the exact mechanisms are not clear. Here, we investigated the effect of the lncRNA ELF3-AS1 on gastric cancer (GC) cell function and explored the exact mechanism. Quantitative real-time polymerase chain reaction was used to detect the expression of ELF3-AS1 in GC tissues and adjacent nontumor tissues. Knockdown and overexpression of ELF3-AS1 was used to detect the effect of ELF3-AS1 on cell function. Potential downstream target genes were identified using RNA transcriptome sequencing, while RNA immunoprecipitation, chromatin immunoprecipitation, and Western blotting were performed to explore the tumor promotion mechanisms of ELF3-AS1. We observed that ELF3-AS1 was highly expressed in GC tissues, and high ELF3-AS1 expression predicted poor prognosis. The knockdown of ELF3-AS1 significantly inhibited cell proliferation, migration, and epithelial-mesenchymal transition and promoted apoptosis. Mechanistic investigations revealed that ELF3-AS1 may regulate the downstream target gene, C-C motif chemokine 20, by binding with the RNA-binding protein hnRNPK. Additionally, we found that high ELF3-AS1 expression was associated with thrombocytosis. Interleukin-6 and thrombopoietin may be involved in ELF3-AS1-induced paraneoplastic thrombocytosis. Together, our results demonstrate that aberrantly expressed ELF3-AS1 in GC may play important roles in oncogenesis and progression and is expected to become a new target for the diagnosis and treatment of GC.

MicroRNA-146b-3p regulates the dysfunction of vascular smooth muscle cells via repressing phosphoinositide-3 kinase catalytic subunit gamma.

MicroRNAs are crucial regulators in the phenotype switch of vascular smooth muscle cells (VSMCs). Nonetheless, the role of miR-146b-3p in VSMCs remains unclear. In the present study, platelet-derived growth factor-BB (PDGF-BB) at different concentrations was employed to stimulate VSMCs for different times, to establish the model of VSMC dysfunction. The relative expression of miR-146b-3p was quantified by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation of VSMCs was measured by BrdU assay. Flow cytometry analysis was employed for the analysis of cell cycle. VSMC migration was detected by Transwell assay. Phosphoinositide-3 kinase catalytic subunit-gamma (PIK3CG) and markers of VSMC differentiation, including α-SMA, SM-22α, SMMHC, and Calponin were examined employing Western blot. The targeting relationship between miR-146b-3p and PIK3CG 3'-UTR was affirmed by dual-luciferase gene assay. We report that the reduction of miR-146b-3p expression was induced by PDGF-BB in a time-dependent and dose-dependent manner (P < 0.05). The overexpression of miR-146b-3p counteracted the effects of PDGF-BB on the proliferation and migration of VSMCs and increased the expressions of differentiation markers (P < 0.05). Additionally, PIK3CG expression was negatively regulated by miR-146b-3p, and the restoration of PIK3CG partly eliminated the effects of miR-146b-3p on VSMCs (P < 0.05). In summary, miR-146b-3p represses the proliferation, migration, and phenotype switch of VSMCs induced by PDGF-BB via targeting PIK3CG. Therefore, miR-146b-3p/PIK3CG may be a potential target for the treatment of atherosclerosis.

A novel long noncoding RNA, TMEM92-AS1, promotes gastric cancer progression by binding to YBX1 to mediate CCL5.

Numerous studies have revealed that long noncoding RNAs (lncRNAs) with oncogene properties play vital roles in gastric cancer (GC). In this study, we aimed to elucidate the function of TMEM92-AS1 in GC progression and to investigate its underlying mechanisms. TMEM92-AS1 was filtered from the Gene Expression Omnibus database. GC tissues and adjacent normal tissues were used to detect the expression level of TMEM92-AS1. MTT, colony-formation assays, Edu, cell cycle, apoptosis and subcutaneous tumour formation assays were used to detect the role of TMEM92-AS1 in cell function. RNA transcriptome sequencing was used to seek downstream target genes. Reverse transcription (RT)-qPCR, western blot, RNA and chromatin immunoprecipitation assays were used to investigate the mechanisms involved. TMEM92-AS1 was significantly overexpressed in GC tissues and correlated with poor overall survival and disease-free survival. Furthermore, TMEM92-AS1 promoted GC cell proliferation and migration in vitro and tumorigenic ability in vivo. RNA transcriptome sequence analysis revealed a potential downstream target gene, C-C motif chemokine ligand 5 (CCL5), and a mechanistic study found that TMEM92-AS1 regulated CCL5 by binding to the transcription factor Y-box binding protein 1(YBX1), which has oncogene properties. In addition, TMEM92-AS1 was found to be associated with peripheral blood leukocyte counts, especially neutrophils. Further investigation found that TMEM92-AS1 may affect leukocytes via regulation of the expression of granulocyte colony-stimulating factor in GC tissues. Our data provide an in-depth insight into the mechanism behind the lncRNA TMEM92-AS1, how it promotes GC progression and the possible mechanism in affecting peripheral leukocyte counts. Therefore, TMEM92-AS1 is a potential target for GC individualized therapy and prognostic assessment.

lncRNA UCA1 Predicts a Poor Prognosis and Regulates Cell Proliferation and Migration by Repressing p21 and SPRY1 Expression in GC.

Dysregulated expression of long non-coding RNAs (lncRNAs) has been reported in many types of cancers, indicating that it has important regulatory roles in human cancer biology. Recently, lncRNA urothelial cancer-associated 1 (UCA1) was shown to be dysregulated in many cancer types, but the detailed mechanisms remain largely unknown. In our study, we found that upregulated UCA1 is associated with poor prognosis in gastric cancer patients. Further experiments revealed that UCA1 knockdown significantly repressed the proliferation and migration both in vitro and in vivo. Moreover, RNA sequencing (RNA-seq) analysis revealed that UCA1 knockdown preferentially affected genes that are linked to cell proliferation, cell cycle, and cell migration. Mechanistically, UCA1 promotes cell proliferation progression through repressing p21 and Sprouty RTK signaling antagonist 1 (SPRY1) expression by binding to EZH2. We found that UCA1 could mediate the trimethylation of H3K27 in promoters of p21 and SPRY1. To our knowledge, this is the first report showing the global gene profile of downstream targets of UCA1 in the progression of gastric cancer. Collectively, our data reveal the important roles of UCA1 in gastric cancer (GC) oncogenesis.

Long Non-coding RNA PVT1 Promotes Cell Proliferation and Migration by Silencing ANGPTL4 Expression in Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is the most common biliary tract malignancy, with a low survival rate and limited treatment options. Long non-coding RNAs (lncRNAs) have recently been verified to have significant regulatory functions in many kinds of human cancers. It was discovered in this study that the lncRNA PVT1, whose expression is significantly elevated in CCA, could be a molecular marker of CCA. Experiments indicated that PVT1 knockdown greatly inhibited cell migration and proliferation in vitro and in vivo. According to RNA sequencing (RNA-seq) analysis, PVT1 knockdown dramatically influenced target genes associated with cell angiogenesis, cell proliferation, and the apoptotic process. RNA immunoprecipitation (RIP) analysis demonstrated that, by binding to epigenetic modification complexes (PRC2), PVT1 could adjust the histone methylation of the promoter of ANGPTL4 (angiopoietin-like 4) and, thus, promote cell growth, migration, and apoptosis progression. The data verified the significant functions of PVT1 in CCA oncogenesis, and they suggested that PVT1 could be a target for CCA intervention.