68Ga-PSMA-11 PET and mpMRI in the diagnosis of initial lymph node staging of prostate cancer: a head-to-head comparative meta-analysis.

Purpose: This meta-analysis evaluates the comparative diagnostic efficacy of 68Ga-prostate-specific membrane antigen-11 PET (68Ga-PSMA-11 PET) and multiparametric MRI (mpMRI) for the initial lymph node staging of prostate cancer. Methods: We searched PubMed and Embase databases through October 2023 for studies that provide a head-to-head comparison of 68Ga-PSMA-11 PET and mpMRI, using pelvic lymph node dissection as the gold standard. We assessed sensitivity and specificity using the DerSimonian and Laird method, with variance stabilization via the Freeman-Tukey double inverse sine transformation. The quality of included studies was evaluated using the Quality Assessment of Diagnostic Performance Studies (QUADAS-2) tool. Results: The meta-analysis incorporated 13 articles, involving a total of 1,527 patients. 68Ga-PSMA-11 PET demonstrated an overall sensitivity of 0.73 (95% CI: 0.51-0.91) and a specificity of 0.94 (95% CI: 0.88-0.99). In comparison, mpMRI showed a sensitivity of 0.49 (95% CI: 0.30-0.68) and a specificity of 0.94 (95% CI: 0.88-0.99). Although 68Ga-PSMA-11 PET appeared to be more sensitive than mpMRI, the differences in sensitivity (p = 0.11) and specificity (p = 0.47) were not statistically significant. Conclusion: Our findings indicated that 68Ga-PSMA-11 PET and mpMRI exhibit similar sensitivity and specificity in the diagnosis of initial lymph node staging of prostate cancer. However, given that most included studies were retrospective, further prospective studies with larger sample sizes are essential to validate these results. Systematic Review Registration: PROSPERO code is CRD42023495266.

Matrix stiffness affects tumor-associated macrophage functional polarization and its potential in tumor therapy.

The extracellular matrix (ECM) plays critical roles in cytoskeletal support, biomechanical transduction and biochemical signal transformation. Tumor-associated macrophage (TAM) function is regulated by matrix stiffness in solid tumors and is often associated with poor prognosis. ECM stiffness-induced mechanical cues can activate cell membrane mechanoreceptors and corresponding mechanotransducers in the cytoplasm, modulating the phenotype of TAMs. Currently, tuning TAM polarization through matrix stiffness-induced mechanical stimulation has received increasing attention, whereas its effect on TAM fate has rarely been summarized. A better understanding of the relationship between matrix stiffness and macrophage function will contribute to the development of new strategies for cancer therapy. In this review, we first introduced the overall relationship between macrophage polarization and matrix stiffness, analyzed the changes in mechanoreceptors and mechanotransducers mediated by matrix stiffness on macrophage function and tumor progression, and finally summarized the effects of targeting ECM stiffness on tumor prognosis to provide insight into this new field.

Risk factors for hypotension in patients with hemodialysis-associated superior vena cava syndrome.

OBJECTIVE: We analyzed the risk factors for hypotension in patients with hemodialysis-associated superior vena cava syndrome (SVCS) and effectiveness of endovascular intervention in hypotension related to SVCS. METHODS: This was a retrospective cohort study. A total of 194 maintenance hemodialysis patients diagnosed with SVCS who were admitted to the Department of Nephrology, West China Hospital of Sichuan University from January 2019 to December 2021 were selected and divided into a hypotension group and a nonhypotension group. Demographic and clinical data were compared. Hypotension simply refers to blood pressure levels of <90/60 mm Hg on a nondialysis day. All patients received endovascular intervention. RESULTS: Hypotension was found in 85 of the 194 patients. The following factors were significantly different between the hypotension and nonhypotension groups: body mass index, history of hypertension, tunneled-cuffed catheter as the means of dialysis access, azygos ectasis, SVC stenosis of >70% or occlusion, occlusion at the cavitary junction, serum calcium, diastolic left ventricular (LV) posterior wall thickness, LV end-diastolic volume, stroke output, and LV ejection fraction. Multivariate logistic regression analysis showed that hypertension history (OR, 0.314; P = .027), tunneled-cuffed catheter as vascular access (OR, 3.997; P < .001), SVC stenosis of >70% or occlusion (OR, 5.243; P < .001), LV posterior wall thickness (OR, 0.772; P = .044), and serum calcium (OR, 0.146; P = .005) were independent risk factors for hypotension. The mean values of systolic and diastolic blood pressure after intravascular treatment were significantly elevated from those before intervention (P < .001). The primary patency rates of SVC were 66.8%, 58.7%, and 50.0% at 3, 6, and 12 months after the procedure. CONCLUSIONS: The incidence of hypotension in patients with hemodialysis-associated SVCS is high. The identification of risk factors of hemodialysis-related hypotension provides insight into potential treatment strategies. Endovascular treatment is expected to improve hypotension related to SVCS in hemodialysis patients.

Identification of a potential prognostic model combining pyroptosis-related gene with immune microenvironment for pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a fatal tumor with grave prognosis. Pyroptosis, a programmed cell death, is involved in tumorigenesis. However, a few studies have elucidated the functions of pyroptosis in PDAC. METHODS: The mRNA expression profiles were downloaded from the TCGA and GEO databases. Univariate and LASSO Cox regression analyses were used to screen out differentially expressed genes (DEGs) and construct the pyroptosis-related genes (PRGs) risk model. The efficiency of model was examined by Kaplan-Meier curve, ROC curve, and nomogram. Univariate and multivariate Cox regression analyses were utilized to assess whether the risk model could be used as an independent prognostic factor. The biological function was analyzed by GO, KEGG, and GSEA enrichment analysis. qRT-PCR and immunohistochemical staining detected gene expression. RESULTS: Totally 9 PRGs with differential expression were identified between normal and PDAC tissues. Then, according to PRGs, we filtered out three key DEGs and constructed the prognostic risk model. Kaplan-Meier curve, ROC curve, and nomogram indicated that the prognostic risk model had high survival prediction efficiency. Meanwhile, the risk model had also shown to be an independent prognostic factor. Further functional enrichment analysis showed that cell adhesion, PI3K-AKT signaling pathway, and dysregulated immune status may be associated with PDAC development. External validation of the model was carried out in the GEO cohort, and the results were similar to that in the TCGA cohort. Finally, the expression of three genes was verified by qRT-PCR and immunohistochemical staining. CONCLUSION: The prognostic risk model established in this study can give a good prediction of the prognosis of PDAC patients, which might provide insights into clinical treatments and prognostic prediction of PDAC.

Cuproptosis-related miRNAs signature and immune infiltration characteristics in colorectal cancer.

BACKGROUND: A novel form of cell death termed cuproptosis was proposed recently. miRNAs play important roles in colorectal cancer (CRC). However, their relationships have not been reported. METHODS: miRNAs that negatively regulate 16 cuproptosis regulators were predicted using Targetscan database. The univariate Cox, LASSO, and multivariate Cox regression analyses were performed to select cuproptosis-related miRNAs. GSEA and ssGSEA analysis was carried out for functional enrichment analysis. The immune cell proportion score (IPS) and the efficiencies of multiple chemotherapy drugs were compared between different risk groups. The CCK8, cell colony, edu, and flow cytometry assays were performed to validate the roles of miRNA. Luciferase reporter assay confirmed the regulatory mechanism of miRNA on cuproptosis. RESULTS: Six cuproptosis-related miRNAs (hsa-miR-653, hsa-miR-216a, hsa-miR-3684, hsa-miR-4437, hsa-miR-641, and hsa-miR-552) were screened out for model construction. The risk score could act as an independent prognostic indicator in CRC (p < 0.001, 95% HR = 1.243 (1.129-1.369)). The nomogram could efficiently predict the overall survival rate (AUC = 0.836). Then, the level of immunosuppressive pathways, immunosuppressive cells, stromal-activated genes, and stromal score was higher in the high-risk group. The IPS analysis showed a better response to immunotherapy in the low-risk group. Also, the risk score was closely correlated with efficiencies of multiple chemotherapy drugs. Furthermore, miR-653 was highly expressed in CRC tissues (p < 0.001), closely correlated with T stage (p < 0.001), metastasis (p < 0.001), and tumor stage (p < 0.001). High expression of miR-653 predicted a shorter overall survival (p = 0.0282) and disease-free survival (p = 0.0056). In addition, miR-653 promoted cell proliferation, inhibited apoptosis, and negatively regulated the expression of DLD through directly binding to the 3'-UTR of DLD mRNA. CONCLUSION: We constructed a cuproptosis-related miRNA signature for the prediction of CRC patient survival and immunotherapy sensitivity. miR-653 was highly expressed in CRC tissues, promoted cell proliferation, and inhibited apoptosis by negatively regulating the expression of DLD.

(-)-Epigallocatechin-3-Gallate Attenuates the Adverse Reactions Triggered by Selenium Nanoparticles without Compromising Their Suppressing Effect on Peritoneal Carcinomatosis in Mice Bearing Hepatocarcinoma 22 Cells.

Increasing evidence shows that selenium and polyphenols are two types of the most reported compounds in tumor chemoprevention due to their remarkable antitumor activity and high safety profile. The cross-talk between polyphenols and selenium is a hot research topic, and the combination of polyphenols and selenium is a valuable strategy for fighting cancer. The current work investigated the combination anti-peritoneal carcinomatosis (PC) effect of selenium nanoparticles (SeNPs) and green tea (Camellia sinensis) polyphenol (-)-epigallocatechin-3-gallate (EGCG) in mice bearing murine hepatocarcinoma 22 (H22) cells. Results showed that SeNPs alone significantly inhibited cancer cell proliferation and extended the survival time of mice bearing H22 cells. Still, the potential therapeutic efficacy is accompanied by an approximately eighty percent diarrhea rate. When EGCG was combined with SeNPs, EGCG did not affect the tumor proliferation inhibition effect but eliminated diarrhea triggered by SeNPs. In addition, both the intracellular selectively accumulated EGCG without killing effect on cancer cells and the enhanced antioxidant enzyme levels in ascites after EGCG was delivered alone by intraperitoneal injection indicated that H22 cells were insensitive to EGCG. Moreover, EGCG could prevent SeNP-caused systemic oxidative damage by enhancing serum superoxide dismutase, glutathione, and glutathione peroxidase levels in healthy mice. Overall, we found that H22 cells are insensitive to EGCG, but combining EGCG with SeNPs could protect against SeNP-triggered diarrhea without compromising the suppressing efficacy of SeNPs on PC in mice bearing H22 cells and attenuate SeNP-caused systemic toxicity in healthy mice. These results suggest that EGCG could be employed as a promising candidate for preventing the adverse reactions of chemotherapy including chemotherapy-induced diarrhea and systemic toxicity in cancer individuals.

NAT10-mediated AXL mRNA N4-acetylcytidine modification promotes pancreatic carcinoma progression.

Although the patient's survival time in various cancers has significantly increased in recent decades, the overall 5-year survival rate of pancreatic ductal adenocarcinoma (PDAC) has remained virtually unchanged due to rapid progression and metastasis. While N-acetyltransferase 10 (NAT10) has been identified as a regulator of mRNA acetylation in many malignancies, its role in PDAC remains unclear. Here, we found that NAT10 mRNA and protein levels were upregulated in PDAC tissues. Increased NAT10 protein expression was significantly correlated with poor prognosis in PDAC patients. Through our experiments, we demonstrated that NAT10 acted as an oncogene to promote PDAC tumorigenesis and metastasis in vitro and in vivo. Mechanistically, NAT10 exerts its oncogenic effects by promoting mRNA stability of receptor tyrosine kinase AXL in an ac4C-dependent manner leading to increased AXL expression and further promoting PDAC cell proliferation and metastasis. Together, our findings highlight the critical of NAT10 in PDAC progression and reveal a novel epigenetic mechanism by which modified mRNA acetylation promotes PDAC metastasis.

Antioxidant, antihyperglycemic, and antihyperlipidemic properties of Chimonanthus salicifolius S. Y. Hu leaves in experimental animals: modulation of thioredoxin and glutathione systems, renal water reabsorption, and gut microbiota.

Introduction: Excessive calorie intake and physical inactivity have dramatically increased nutrient overload-associated disease, becoming a global public health issue. Chimonanthus salicifolius S. Y. Hu (CHI) is a homology plant of food and medicine in China and shows several health benefits. Methods: This work investigated the antioxidant activity, the alleviating effects, and the mechanism of action on diabetes and hyperlipidemia of CHI leaves. Results and discussion: Results showed that CHI leaves infusion displayed in vitro antioxidant activity measured by ABTS and ferric reducing antioxidant power methods. In wild-type Kunming mice, CHI leaves infusion consumption activated the hepatic antioxidant enzymes, including glutathione reductase, glutathione S-transferase, glutathione peroxidase and thioredoxin reductase as well as thioredoxin reductase 1. In alloxan-induced type 1 diabetic mice, CHI leaves infusion ameliorated diabetic symptoms, including polyuria, polydipsia, polyphagia and hyperglycemia, in a dose-dependent and time-course manners. The mechanism involved CHI leaves up-regulating renal water reabsorption associated protein - urine transporter A1-and promoting the trafficking of urine transporter A1 and aquaporin 2 to the apical plasma membrane. Despite this, in high-fat diet-induced hyperlipidemic golden hamsters, CHI leaves powder did not significantly effect on hyperlipidemia and body weight gain. This might be attributed to CHI leaves powder increasing the calorie intake. Interestingly, we found that CHI leaves extract containing a lower dose of total flavonoid than CHI leaves powder pronouncedly reduced the levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol in serum in golden hamsters fed a high-fat diet. Furthermore, CHI leaves extract elevated the diversity of gut microbiota and the abundance of Bifidobacterium and Ruminococcaceae_UCG-014. It also decreased the abundance of Lactobacillus at the genus level in golden hamsters fed a high-fat diet. Overall, CHI leaves benefit oxidative stress prevention and metabolic syndrome amelioration in vivo.

Percutaneous superior vena cava puncture for hemodialysis catheter placement.

OBJECTIVE: Central venous occlusion (CVO) refractory to endovascular angioplasty is a critical challenge that threatens hemodialysis vascular access. In the present study, we evaluated the efficacy and safety of tunneled, cuffed central venous catheter (tCVC) placement via percutaneous superior vena cava (SVC) puncture in patients with refractory CVO. METHODS: Patients requiring maintenance hemodialysis with refractory CVO who had undergone percutaneous SVC puncture and tCVC insertion at a university-affiliated hospital from January 2016 to June 2020 were included. The patients were followed up until May 2021. The demographic information, complications, and catheter patency were analyzed. RESULTS: A total of 205 patients (105 women [51.2%]; mean age, 61 ± 15 years) were included. The SVC puncture and tCVC insertion were successfully performed in 194 patients, for a technical success rate of 94.6%. One patient had experienced a pleura injury and hemothorax and had required urgent thoracotomy. A total of 37 patients had presented with mild chest pain and were prescribed oral nonsteroidal anti-inflammatory drugs. During follow-up of the 194 patients with a successful procedure, catheter dysfunction due to thrombosis had occurred in 66 patients, catheter malposition had occurred in 5 patients, and catheter-related blood stream infection had developed in 6 patients. The 3-year primary patency rate was 64.2%, and the 3-year secondary patency rate was 76.3%. CONCLUSIONS: A tCVC placed through a percutaneous SVC puncture had a satisfactory technical success rate and long-term patency rate in patients requiring hemodialysis, providing an optional vascular access for those with exhausted central vein resources. SVC puncture also avoided the use of left-sided catheters and preserved central vein resources. Caution should be given to avoid potential complications such as pleura injury and hemothorax.

Comprehensive analysis of cuproptosis-related lncRNAs to predict prognosis and immune infiltration characteristics in colorectal cancer.

Background: Cuproptosis is a novel form of cell death discovered in recent. A great quantity of researches has confirmed the close relationships and crucial roles between long non-coding RNAs (lncRNAs) with the progression of colorectal cancer (CRC). However, the relationship between cuproptosis and lncRNAs remains unclear in CRC. Methods: 1,111 co-expressed lncRNAs with 16 cuproptosis regulators were retrieved from CRC samples of The Cancer Genome Atlas (TCGA) database. Through univariate Cox and least absolute shrinkage and selection operator regression analysis, a prognosis model was constructed with 15 lncRNAs. The Kaplan-Meier, receiver operating characteristic curve, C-index and principal component analysis identified the prognostic power. Furthermore, a cuproptosis-related cluster was generated based on the 15 lncRNAs by unsupervised methods. The correlations between the cuproptosis-related signatures with immune cell infiltration and anti-tumor therapy were explored by multiple algorithms. Results: A risk score and nomogram with great prediction ability were constructed for CRC prognosis evaluation. The immune activate pathways, immune infiltration cells, immune functions, immune score and immune activation genes were remarkably enriched in the high risk group. The cuproptosis-related cluster was generated, of which the cluster 2 showed longer overall survival. The immune cell infiltration analysis indicated the similar results of cluster 2 with the high risk group, implying a significant marker for "hot tumor." The cluster 2 also presented high expression of immune checkpoint molecules, MSI-H status and higher susceptibility to multiple immunotherapy drugs. Conclusion: We appraised a novel cuproptosis-related prognosis model and molecular signature associated with prognosis, immune infiltration and immunotherapy. The identification of cuproptosis-related lncRNAs improved our understanding of immune infiltration and provided a significant marker for prognosis and immunotherapy in CRC.

Decidual macrophages in recurrent spontaneous abortion.

Recurrent spontaneous abortion (RSA) is defined as two or more pregnancy loss, affecting the happiness index of fertility couples. The mechanisms involved in the occurrence of RSA are not clear to date. The primary problem for the maternal immune system is how to establish and maintain the immune tolerance to the semi-allogeneic fetuses. During the pregnancy, decidual macrophages mainly play an important role in the immunologic dialogue. The purpose of this study is to explore decidual macrophages, and to understand whether there is a connection between these cells and RSA by analyzing their phenotypes and functions. Pubmed, Web of Science and Embase were searched. The eligibility criterion for this review was evaluating the literature about the pregnancy and macrophages. Any disagreement between the authors was resolved upon discussion and if required by the judgment of the corresponding author. We summarized the latest views on the phenotype, function and dysfunction of decidual macrophages to illuminate its relationship with RSA.

Hypoxia-induced circRNF13 promotes the progression and glycolysis of pancreatic cancer.

Pancreatic cancer (PC) is one of the most malignant tumors. Rapid progression and distant metastasis are the main causes of patient death. Hypoxia is a hallmark of multiple cancers and is involved in tumor biology. However, little is known about the roles of circRNAs in glycolysis and hypoxia-mediated progression of PC. Here, the expression pattern of hypoxia-related circRNAs was analyzed using RNA sequencing. A unique circRNA termed circRNF13 was found to be upregulated in PC tissues and may be a potential prognostic indicator. HIF-1α and EIF4A3 are involved in regulating the biogenesis of circRNF13. Furthermore, circRNF13 was validated to exert a stimulative effect on cell proliferation, angiogenesis, invasion and glycolysis. Importantly, we found that circRNF13 promoted PDK3 levels by acting as a miR-654-3p sponge, thus promoting the PC malignant process. Collectively, our results reveal that hypoxia-induced circRNF13 mediated by HIF-1α and EIF4A3 promotes tumor progression and glycolysis in PC, indicating the potential of circRNF13 as a prognostic biomarker and therapeutic target for PC.

A novel cuproptosis-related molecular pattern and its tumor microenvironment characterization in colorectal cancer.

Cuproptosis, or copper-induced cell death, has been reported as a novel noncanonical form of cell death in recent times. However, the potential roles of cuproptosis in the alteration of tumor clinicopathological features and the formation of a tumor microenvironment (TME) remain unclear. In this study, we comprehensively analyzed the cuproptosis-related molecular patterns of 1,274 colorectal cancer samples based on 16 cuproptosis regulators. The consensus clustering algorithm was conducted to identify cuproptosis-related molecular patterns and gene signatures. The ssGSEA and ESTIMATE algorithms were used to evaluate the enrichment levels of the infiltrated immune cells and tumor immune scores, respectively. The cuproptosis score was established to assess the cuproptosis patterns of individuals with principal component analysis algorithms based on the expression of cuproptosis-related genes. Three distinct cuproptosis patterns were confirmed and demonstrated to be associated with distinguishable biological processes and clinical prognosis. Interestingly, the three cuproptosis patterns were revealed to be consistent with three immune infiltration characterizations: immune-desert, immune-inflamed, and immune-excluded. Enhanced survival, activation of immune cells, and high tumor purity were presented in patients with low cuproptosisScore, implicating the immune-inflamed phenotype. In addition, low scores were linked to high tumor mutation burden, MSI-H and high CTLA4 expression, showing a higher immune cell proportion score (IPS). Taken together, our study revealed a novel cuproptosis-related molecular pattern associated with the TME phenotype. The formation of cuproptosisScore will further strengthen our understanding of the TME feature and instruct a more personalized immunotherapy schedule in colorectal cancer.

RELA-induced MiR-21 Exerts Oncogenic Effects on PDAC via Targeting of ARHGAP24.

Inflammation is one of the inducing factors of pancreatic ductal adenocarcinoma (PDAC), and microRNAs have been confirmed to be involved in the occurrence and development of PDAC. However, whether RELA, an inflammatory regulator, is involved in the regulation of PDAC by miRNA remains to be further studied. In the present study miR-21 was characterized and its upstream regulatory mechanism was investigated, as well as its functional effects and target genes in pancreatic ductal adenocarcinoma (PDAC). In situ hybridization analysis confirmed increased miR-21 expression levels in PDAC tissues. The results of the chromatin immunoprecipitation and dual-luciferase reporter assays demonstrated that transcription factor RELA modulated miR-21 transcription in the PDAC, PANC-1 and MIA PaCa-2 cell lines. Subsequently, a cell viability assay, EdU staining assay and flow cytometry analysis, demonstrated that miR-21 promoted cell proliferation and cell cycle progression, but inhibited cell apoptosis in vitro. Furthermore, a xenograft assay demonstrated that miR-21 accelerated tumor growth in vivo. Mechanistically, miR-21 directly regulated the expression of Rho GTPase activating protein 24 (ARHGAP24), which was indicated to be a tumor suppressor gene. Moreover, both miR-21 and ARHGAP24 were strongly associated with clinical features and may therefore serve as valuable biomarkers in PDAC prognosis.

Peptide amphiphile inspired self-assembled, ordered gold nanocomposites for improved sensitivity of electrochemical immunosensor: Applications in determining the total aflatoxin amount in food stuffs.

In peptide amphiphile, The positively charged amino acid arginine can inspire the ordered self-assembly of gold nanocomposites (AuNPs), transfer positive charge to AuNPs, and weaken the aggregation of AuNPs by electrostatic repulsion, whereas hydrophobic fatty acid chains regulate the self-assembly of AuNPs through hydrophobic interaction, which may be a novel strategy to overcome disordered arrangement and aggregation of AuNPs to obtain an ultra-sensitive electrochemical immunosensor for determining the total aflatoxin amount. In this study, a peptide amphiphile (C14R5), composed of five arginine residues as the hydrophilic chain and myristic acid as the hydrophobic chain, inspired AuNPs to form monodispersed hollow raspberry-like AuNPs (rasAuNPs). rasAuNPs could captured and immobilized large amounts of aflatoxin antigens via the Au-S bonds, resulting in binding to more anti-aflatoxin antibodies. In the absence of aflatoxins, the enriched antigens bound to abundant antibodies, resulting in a low blank signal current. By contrast, in the presence of aflatoxins, enough antibodies could bind to the targets and less antibodies could recognize the antigens, increasing the detection signal intensity. Under the optimal conditions, the developed sensor demonstrated a wide linear range (0.13-29.06 pg mL-1) and a low limit of detection for total aflatoxins (0.05 pg mL-1) using a mixed standard (AFB1: AFB2: AFG1: AFG2 with a weight ratio of 1:1:1:1) in peanut, peanut milk, and maize powder samples. Hence, this novel strategy improves the sensitivity of electrochemical sensors and can be easily applied to detect other small molecule compound for the purpose of food safety.

Circular RNA circ_0047744 suppresses the metastasis of pancreatic ductal adenocarcinoma by regulating the miR-21/SOCS5 axis.

There is increasing evidence that circular RNAs (circRNAs) can serve as microRNA (miRNA) sponges to regulate metastasis of multiple tumors, including pancreatic ductal adenocarcinoma (PDAC). However, the role of the circRNA/miRNA regulatory network in metastasis of PDAC has not been elucidated. The purpose of this study is to explore the role of circ_0047744/miR-21/SOCS5 in the metastasis of PDAC. We found that circRNA_0047744 was weakly expressed in PDAC tissues and cell lines. The expression of circ_0047744 was negatively correlated with lymph node metastasis and positively correlated with overall survival in PDAC patients. Functionally, the overexpression of circ_0047744 suppressed cell migration and invasion in vitro and in vivo. Mechanistically, circ_0047744 could regulate SOCS5 expression by acting as a sponge of miR-21 to inhibit migration and invasion of PDAC cells. Our study demonstrates that circ_0047744 acts as an anti-oncogene to inhibit PDAC metastasis by regulating the miR-21/SOCS5 axis, indicating that circ_0047744 may be a potential novel therapeutic target for PDAC patients.

Long noncoding RNA LINC00958 suppresses apoptosis and radiosensitivity of colorectal cancer through targeting miR-422a.

BACKGROUND: Long noncoding RNAs (lncRNAs) have been elucidated to participate in the development and progression of various cancers. In this study, we aimed to explore the underlying functions and mechanisms of LINC00958 in colorectal cancer. METHODS: LINC00958 expression in colorectal cancer tissues was examined by qRT-PCR. The correlations between LINC00958 expression and clinical characteristics and prognosis were evaluated. The biological functions of LINC00958 were detected by CCK-8, MTT, colony formation and flow cytometric analyses. RNA pulldown, RIP and luciferase reporter assays were used to confirm the regulatory effects of LINC00958 on miR-422a. Rescue experiments were performed to detect the effects of miR-422a on the roles of LINC00958. RESULTS: LINC00958 was upregulated in colorectal cancer tissues and cell lines. High LINC00958 levels were positively associated with T stage and predicted poor prognosis. Cell experiments showed that LINC00958 promoted cell proliferation and suppressed apoptosis and sensitivity to radiotherapy in vitro and promoted tumor growth in vivo. Bioinformatics analysis predicted the binding site of miR-422a on LINC00958. Mechanistically, RNA pulldown, RIP and luciferase reporter assays demonstrated that LINC00958 specifically targeted miR-422a. In addition, we found that miR-422a suppressed MAPK1 expression by directly binding to the 3'-UTR of MAPK1, thereby inhibiting cell proliferation and enhancing cell apoptosis and radiosensitivity. Furthermore, miR-422a rescued the roles of LINC00958 in promoting MAPK1 expression and cell proliferation and decreasing cell apoptosis and radiosensitivity. CONCLUSIONS: LINC00958 promoted MAPK1 expression and cell proliferation and suppressed cell apoptosis and radiosensitivity by targeting miR-422a, which suggests that it is a potential biomarker for the prognosis and treatment of colorectal cancer.

ELK3 Mediated by ZEB1 Facilitates the Growth and Metastasis of Pancreatic Carcinoma by Activating the Wnt/ß-Catenin Pathway.

Rapid progression and metastasis are the major causes of death in patients with pancreatic ductal adenocarcinoma (PDAC). ELK3, a member of the ternary complex factor (TCF), has been associated with the initiation and progression of various cancers. However, the role of ELK3 in PDAC is not yet fully understood. Online databases and immunohistochemistry were used to analyze the ELK3 levels in PDAC tissues. The function of ELK3 was confirmed by a series of in vivo and in vitro studies. Western blotting and immunofluorescence were used to detect the molecular mechanisms of PDAC. ChIP-qPCR was used to study the mechanism responsible for the elevation of ELK3 expression in PDAC. The ELK3 levels were higher in PDAC tissues than in adjacent normal tissues. Functionally, we demonstrated that ELK3 acted as an oncogene to promote PDAC tumorigenesis and metastasis. Further study suggested that ELK3 promoted PDAC cell migration and invasion by activating the Wnt/ß-catenin pathway, and proved that ZEB1 could directly bind to the promoter of ELK3 to increase its transcription. Finally, both were associated with the patients' clinicopathological features and worse overall survival. Conclusively, our findings enrich the role of ELK3 in PDAC, and provide potential avenues for exploring more effective biomarkers and therapeutic strategies for the treatment of PDAC.