Marshalllong6871
RUNX1-IT1 suppresses colorectal cancer and liver cancer, while its role in other cancers is unknown. This study was performed to investigate the role of RUNX1-IT1 in endometrial cancer (EC).
EC and paired non-tumor tissues were collected from 62 EC patients, and the expression of RUNX1-IT1, mature miR-21 and miR-21 precursor in these tissue samples were determined by RT-qPCR. Correlations were analyzed by linear regression. Overexpression of RUNX1-IT1 was achieved in EC cells and the expression of mature miR-21 and miR-21 precursor were analyzed by RT-qPCR. CCK-8 assay was used for cell proliferation analysis.
We found that RUNX1-IT1 was downregulated in EC and inversely correlated with mature miR-21 but not miR-21 precursor. RUNX1-IT1 was predicted to bind with miR-21 precursor. The interaction between them was verified by dual-luciferase activity assay and RNA pull-down assay. In EC cells, overexpression of RUNX1-IT1 downregulated mature miR-21, but not miR-21 precursor. Overexpression of RUNX1-IT1 suppressed the role of miR-21 in increasing cell proliferation.
RUNX1-IT1 is downregulated in EC and inhibits cancer cell proliferation by suppressing the maturation of miR-21.
RUNX1-IT1 is downregulated in EC and inhibits cancer cell proliferation by suppressing the maturation of miR-21.
Renal cell carcinoma (RCC) is one of the most common malignancies globally, among which clear cell carcinoma (ccRCC) accounts for 85-90% of all pathological types. This study aims to screen out potential genes in metastatic ccRCC so as to provide novel insights for ccRCC treatment.
GSE53757 and GSE84546 datasets in the Gene Expression Omnibus (GEO) were profiled to identify differentially expressed genes (DEGs) from ccRCC samples with or without metastasis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and the gene ontology (GO) analysis were performed to analyze pathway enrichment and functional annotation of DEGs. Protein-protein interaction (PPI) network was constructed, and survival analysis was conducted to evaluate the clinical values of the identified hub genes. In vitro loss-of-function assays were performed to explore the biological roles of these genes.
The bioinformatic analysis indicated that 312 DEGs were identified, including 148 upregulated genes and 164 downregulated ones. Using PPI and Cytoscape, 10 hub genes were selected (
,
,
,
,
,
,
,
,
, and
) from DEGs which might be closely related with ccRCC metastasis. In Kaplan-Meier analysis, three potential prognostic biomarkers (
,
and
) were identified. Finally, cell proliferative and invasive assays further verified that
,
and
were associated with the proliferation and invasion of ccRCC cells.
Our results demonstrated that metastatic ccRCC was partially attributed to the aberrant expression of
,
and
, and more personalized therapeutic approaches should be explored targeting these hub genes.
Our results demonstrated that metastatic ccRCC was partially attributed to the aberrant expression of KIF20A, CCNB2 and CDCA8, and more personalized therapeutic approaches should be explored targeting these hub genes.
The acquisition of chemoresistance to methotrexate (MTX) still remains one of the major challenges for choriocarcinoma treatment. Herein, we aimed to evaluate the potential role of Signaling Lymphocytic Activation Molecule Family Member 1 (SLAMF1) as a possible regulator of chemoresistance to MTX in choriocarcinoma.
MTX-resistant JEG3 and JAR sublines (JEG3/MTX, JAR/MTX) were used to study SLAMF1 function. CCK8 assay and soft agar assay were conducted to measure the cell viability and clonogenesis of choriocarcinoma cells, respectively; MDC incorporation assay was conducted for the quantification of intracellular autophagy; BrdU labeling was used to assess the proliferative potential of choriocarcinoma cells; SLAMF1 protein expression was analyzed by Western blotting.
Upregulation of SLAMF1 expression was observed in MTX-resistant JEG3/MTX and JAR/MTX sublines compared to their parental JEG3 and JAR cell lines, respectively. Knockdown of SLAMF1 markedly attenuated cell viability and soft agar clonogenesful therapeutic strategy to sensitize choriocarcinoma cells to MTX-based regimens.
Medulloblastoma (MB) is the most common malignant brain tumor during childhood. Circular RNA (circSKA3) was identified to function as an oncogene in MB. However, the mechanism of circSKA3 in MB remains unclear.
The levels of circSKA3, microRNA-383-5p (miR-383-5p), and forkhead box M1 (
) in MB tissues were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The cell viability and apoptotic rate were assessed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry, respectively. The protein levels of B-cell lymphoma 2 (Bcl-2), C-Caspase3, and FOXM1 were detected via Western blot assay. Cell cycle was detected by flow cytometry. The migration and invasion abilities were monitored by Transwell assay. The dual-luciferase reporter assay was constructed to verify the interactions between miR-383-5p and circSKA3 or
. The mice model experiment was carried out to validate the effects of circSKA3 in vivo.
The levels of circSKA3 and
were significantly elevated, while the level of miR-383-5p was notably declined in MB tissues. CircSKA3 was validated to sponge miR-383-5p, and
was a candidate target of miR-383-5p. ARRY-575 solubility dmso CircSKA3 silencing impeded cell proliferation, migration, and invasion while promoted apoptosis by targeting miR-383-5p in vitro and retarded xenograft tumor growth in vivo. miR-383-5p suppressed cell proliferation, migration, and invasion but promoted apoptosis in MB cells by regulating FOXM1. CircSKA3 depletion decreased
expression via miR-383-5p in MB cells.
CircSKA3 augmented MB progression partly through miR-383-5p/
axis.
CircSKA3 augmented MB progression partly through miR-383-5p/FOXM1 axis.
Thyroid cancer (TC) is an endocrine tumor whose risk of onset has been rising, so the deep understanding of its molecular mechanism helps formulate new treatment strategies.
This paper was aimed at exploring the regulatory mechanism of long non-coding RNA (LncRNA) plasmacytoma variant translocation 1 (PVT1) in TC. The expression of PVT1, miR-423-5p and p21-activated kinase 3 (PAK3) in TC tissues and cell lines was detected by real-time PCR. PAK3 levels were detected by Western blot. Regulatory relationships between target genes and the proliferation, invasion and apoptosis of cells and genes were analyzed.
PVT1 and PAK3 upregulated while miR-423-5p downregulated in the tissues and cell lines. PVT1 downregulation inhibited TC cells from malignantly proliferating and invading, and promoted their apoptosis. PVT1 specifically regulated miR-423-5p, and its overexpression could weaken the anti-tumor effect of this miR on TC cells. In addition, miR-423-5p directly targeted PAK3, and knocking down its expression could weaken the inhibitory effect of PAK3 downregulation on TC progression. Besides, PVT1 acted as a competitive endogenous RNA to sponge this miR and thus regulate PAK3 expression.
In conclusion, PVT1 can mediate the molecular mechanism of the miR-423-5p-PAK3 axis regulatory network on regulating TC, so it is a new direction of treating the disease.
In conclusion, PVT1 can mediate the molecular mechanism of the miR-423-5p-PAK3 axis regulatory network on regulating TC, so it is a new direction of treating the disease.
Evaluate changes from baseline in health-related quality of life (QoL) in Japanese patients with episodic migraine receiving preventive treatment with galcanezumab (GMB).
Preventive treatments for migraine have been shown to improve QoL, but few clinical trials have examined QoL outcomes in Japanese patients. This phase 2, randomized, double-blind, placebo-controlled study was conducted at 40 centers in Japan. Patients aged 18-65 years with episodic migraine (4-14 monthly migraine headache days) received GMB 120 mg (n=115), 240 mg (n=114), or placebo (PBO, n=230) as monthly subcutaneous injections for 6 months. QoL was measured monthly using the Migraine-Specific Quality-of-Life Questionnaire (MSQ) version 2.1. Prespecified analyses were differences between GMB and PBO for change from baseline in all 3 domains of the MSQ and MSQ-Total, for each month and the average over Months 4-6.
Treatment with GMB significantly increased MSQ scores from baseline vs PBO. Average change ± SE from baseline across Monthered November 7, 2016).
ClinicalTrials.gov, NCT02959177 (registered November 7, 2016).
Despite the increasing prevalence of opioid use disorder (OUD) in pregnant women, there are limited studies on their anesthesia care and analgesic outcomes after cesarean delivery (CD).
Patients with OUD on either buprenorphine or methadone maintenance therapy who underwent CD at our institution from 2011 to 2018 were identified. Anesthetic details and analgesic outcomes, including daily opioid consumption and pain scores, were compared between patients maintained on buprenorphine and methadone. Analgesic outcomes were also evaluated according to anesthetic type (neuraxial or general anesthesia) and daily buprenorphine/methadone dose to determine if these factors impacted pain after delivery.
A total of 146 patients were included (buprenorphine n=99 (67.8%), methadone n=47 (32.2%)). Among all patients 74% had spinal/CSE, 15% epidural, and 11% general anesthesia. Anesthesia types were similar among buprenorphine and methadone patients. For spinal anesthetics, intrathecal fentanyl (median 15 µg) and morph as a useful reference for future prospective investigations and aid in the clinical care of these patients.
Patients on buprenorphine and methadone had similar high opioid consumption and pain scores after CD. The anesthetic details and analgesic outcomes reported in this investigation may serve as a useful reference for future prospective investigations and aid in the clinical care of these patients.
Identifying patients with atherosclerotic renal artery stenosis (ARAS) who will be improved in renal function after percutaneous transluminal renal artery stenting (PTRAS) is crucial since most patients show no worthwhile benefit of PTRAS. Although the assessment of renal parenchymal perfusion is useful for the identification, few studies predict the renal functional improvement by evaluating the characteristics of renal perfusion.
The aim of this study was to assess the renal parenchymal perfusion in ARAS patients with contrast-enhanced ultrasonography (CEUS) and predict the benefits of renal function after PTRAS utilizing time-intensity curve (TIC) parameters.
Thirty-eight kidneys in 30 ARAS patients received PTRAS in this study. They were divided into moderate stenosis group (n=25) and severe stenosis group (n=13) and mild dysfunction group (n=14) and moderate dysfunction group (n=24) according to the degree of renal stenosis and radioisotope glomerular filtration rate (rGFR). The baseline assessment after PTRAS.
CEUS could accurately assess renal parenchymal perfusion and identify ARAS patients with potential benefit after PTRAS. The combination of TIC parameters (AUC and PI) is valuable in the prediction of improved renal function after PTRAS.
