Identification and diagnostic potential of hsa_circ_101303 in colorectal cancer: unraveling a regulatory network.

BACKGROUND: The role of novel circular RNAs (circRNAs) in colorectal cancer (CRC) remains to be determined. This study aimed to identify a novel circRNA involved in CRC pathogenesis, assess its diagnostic value, and construct a regulatory network. METHODS: Differential expression analysis was conducted using circRNA datasets to screen for differentially expressed circRNAs. The expression of selected circRNAs was validated in external datasets and clinical samples. Diagnostic value of plasma circRNA levels in CRC was assessed. A competing endogenous RNA (ceRNA) network was constructed for the circRNA using TCGA dataset. RESULTS: Analysis of datasets revealed that hsa_circ_101303 was significantly overexpressed in CRC tissues compared to normal tissues. The upregulation of hsa_circ_101303 in CRC tissues was further confirmed through the GSE138589 dataset and clinical samples. High expression of hsa_circ_101303 was associated with advanced N stage, M stage, and tumor stage in CRC. Plasma levels of hsa_circ_101303 were markedly elevated in CRC patients and exhibited moderate diagnostic ability for CRC (AUC = 0.738). The host gene of hsa_circ_101303 was also found to be related to the TNM stage of CRC. Nine miRNAs were identified as target miRNAs for hsa_circ_101303, and 27 genes were identified as targets of these miRNAs. Subsequently, a ceRNA network for hsa_circ_101303 was constructed to illustrate the interactions between the nine miRNAs and 27 genes. CONCLUSIONS: The study identifies hsa_circ_101303 as a highly expressed circRNA in CRC, which is associated with the progression of the disease. Plasma levels of hsa_circ_101303 show promising diagnostic potential for CRC. The ceRNA network for hsa_circ_101303 provides valuable insights into the regulatory mechanisms underlying CRC.

Multimodal imaging findings of sarcomatoid carcinoma of the urinary bladder.

Sarcomatoid carcinoma, a rare and aggressive subtype of bladder cancer, accounting for 0.3% of cases, is more aggressive than urothelial carcinomas. Accurate diagnosis, crucial for treatment, can be challenging. We present a characterized case of sarcomatoid carcinoma of the urinary bladder using multimodal imaging and pathology.

Ultrasonographic and pathological findings of syringocystadenoma papilliferum in the skin.

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Imaging findings of succinate dehydrogenase-deficient renal cell carcinoma.

Key Clinical Message: A 50-year-old man with a mass located in the left kidney was described by multimodal images, including ultrasonography, computed tomography, and magnetic resonance imaging. After surgical resection of the mass, pathological examination confirmed succinate dehydrogenase-deficient renal cell carcinoma. Abstract: Succinate dehydrogenase-deficient renal cell carcinoma (SDH-deficient RCC) is a malignant tumor in the kidney associated with the loss of mitochondrial enzyme II. Due to its rarity, SDH-deficient RCC is frequently misdiagnosed. We present multimodal imaging and pathologic findings in a 50-year-old male with SDH-deficient RCC.

Local Sustained Chemotherapy of Pancreatic Cancer Using Endoscopic Ultrasound-Guided Injection of Biodegradable Thermo-Sensitive Hydrogel.

Purpose: Endoscopic ultrasound-guided fine-needle injection (EUS-FNI) offers a promising minimally invasive approach for locally targeted management of advanced pancreatic cancer. However, the efficacy is limited due to the rapid plasma clearance of chemotherapeutic agents. Injectable hydrogels can form drug release depots, which provide a feasible solution for optimizing targeted chemotherapy through EUS-FNI. Methods: A drug delivery system was developed, consisting of gemcitabine (GEM) and thermo-sensitive hydrogel (PLGA-PEG-PLGA, PPP). The injectability, gel formation ability, biocompatibility and sustained drug delivery properties of PPP hydrogel were verified in vitro and in vivo. The effects of GEM/PPP hydrogel on cell proliferation, invasion, metastasis, and apoptosis were explored through co-culturing with PANC-1 cells. The therapeutic effects of GEM/PPP hydrogel on xenograft mice were compared with those of GEM, ethanol and polidocanol using the precisely targeted EUS-FNI technology. Tumor sections were examined by H&E, Ki-67, and TUNEL staining. Results: GEM/PPP hydrogel exhibited excellent injectability, biocompatibility, and the capability of sustained drug delivery for up to 7 days by forming a gel triggered by body temperature. It demonstrated the best therapeutic effects, significantly reducing proliferation, invasion and migration of PANC-1 cells while promoting apoptosis. After precise injection using EUS-FNI technology, GEM/PPP hydrogel resulted in a reduction of tumor weight by up to 75.96% and extending the survival period by 14.4 days with negligible adverse effects. Pathological examination revealed no systemic toxicity and significant apoptosis and minimal proliferation as well. Conclusion: The combination of GEM/PPP hydrogel and EUS-FNI technology provides an optimal approach of precise chemotherapy for pancreatic cancer, builds a bridge for clinical translation of basic research, and brings great hope for innovation of minimally invasive treatment modalities. The first-hand EUS image data obtained in this study also serves as a crucial reference for future clinical trials.

Long noncoding RNA GHET1 promotes cell proliferation through oxidative stress in prostate cancer.

Gastric carcinoma high expressed transcript 1 (GHET1) is an oncogenic Long noncoding RNA. GHET1 expression promotes multiple levels of developing a complex molecular network. The main purpose of the study was to investigate the mechanism by which long noncoding RNA (lncRNA) GHET1 promotes prostate cancer cell proliferation and related metabolism. In vitro study, lncRNA GHET1 was overexpressed in LN-cap, PC-3, 22RV1, and C4-2 cells. The cell viability was measured by MTT and trans-well assay. A flow cytometer was also used to detect cell cycles and apoptosis. Western blot analysis was used for protein expression validation. mRNA expression was detected by real-time PCR. lncRNA GHET1 enhanced cell proliferation, migration, and could resist paclitaxel-induced apoptosis and cell cycle arrest GHET1 expression stimulates reactive oxygen species (ROS) level upregulated in prostate cancer cells, increased the expression of HIFα, IL-1B and IL-6, and activated ROS/STAT-3/Twsit1 signaling pathway. Knockdown GHET1 could reduce cell proliferation and migration due to the overexpression of GHET1. lncRNA GHET1 promotes prostate cancer growth through oxidative stress signaling pathways and resists the antineoplastic drug paclitaxel, which can be used as a target for antineoplastic therapy and drug resistance therapy in the future in clinics.

Identification of ZBTB4 as an immunological biomarker that can inhibit the proliferation and invasion of pancreatic cancer.

BACKGROUND: Zinc finger and BTB domain-containing protein 4 (ZBTB4) belongs to the zinc finger protein family, which has a role in regulating epigenetic inheritance and is associated with cell differentiation and proliferation. Previous studies have identified aberrant ZBTB4 expression in cancer and its ability to modulate disease progression, but studies on the immune microenvironment, immunotherapy and its role in cancer are still lacking. METHODS: Human pan-cancer and normal tissue transcriptome data were obtained from The Cancer Genome Atlas. The pan-cancer genomic alteration landscape of ZBTB4 was investigated with the online tool. The Kaplan-Meier method was used to evaluate the prognostic significance of ZBTB4 in pancreatic cancer. In parallel, ZBTB4 interacting molecules and potential functions were analyzed by co-expression and the correlation between ZBTB4 and immune cell infiltration, immune modulatory cells and efficacy of immune checkpoint therapy was explored. Next, we retrieved the Gene Expression Omnibus database expression datasets of ZBTB4 and investigated ZBTB4 expression and clinical significance in pancreatic cancer by immunohistochemical staining experiments. Finally, cell experiments were performed to investigate changes in pancreatic cancer cell proliferation, migration and invasion following overexpression and knockdown of ZBTB4. FINDINGS: ZBTB4 showed loss of expression in the majority of tumors and possessed the ability to predict cancer prognosis. ZBTB4 was closely related to the tumor immune microenvironment, immune cell infiltration and immunotherapy efficacy. ZBTB4 had good diagnostic performance for pancreatic cancer in the clinic, and ZBTB4 protein expression was lost in pancreatic cancer tumor tissues. Cell experiments revealed that overexpression of ZBTB4 inhibited the proliferation, migration and invasion of pancreatic cancer cells, while silencing ZBTB4 showed the opposite effect. CONCLUSIONS: According to our results, ZBTB4 is present in pancreatic cancer with aberrant expression and is associated with an altered immune microenvironment. We show that ZBTB4 is a promising marker for cancer immunotherapy and cancer prognosis and has the potential to influence pancreatic cancer progression.

The Long Noncoding RNA Gm9866/Nuclear Factor-κB Axis Promotes Macrophage Polarization.

Macrophages are a type of immune cells with high levels of plasticity and heterogeneity. They can polarize into M1 or M2 functional phenotypes. These two phenotypes exhibit a dynamic balance during polarization-related diseases and play opposing roles. Long noncoding RNAs (lncRNAs) play an important role in biological processes such as cell proliferation, death, and differentiation; however, how long noncoding RNAs affect the cellular functionality of macrophages remains to be studied. Long noncoding RNA Gm9866 was found to be closely related to macrophage polarization through bioinformatics analysis. In this study, by conducting real-time polymerase chain reaction analysis, it was observed that long noncoding RNA Gm9866 expression significantly increased after treatment with interleukin-4 but significantly decreased after treatment with lipopolysaccharide. Fluorescence in situ hybridization revealed that long noncoding RNA Gm9866 was expressed mainly in the nucleus. Real-time polymerase chain reaction analysis showed that overexpression of long noncoding RNA Gm9866 in RAW264.7 cells further promoted the expression of M2 markers MRC1 (macrophage mannose receptor 1) and MRC2 (macrophage mannose receptor 2). Western blotting analysis demonstrated inhibition of nuclear factor-κB (NF-κB) expression. EdU (5-ethynyl-2'-deoxyuridine) and TUNEL (TdT-mediated dUTP nick-end labeling) staining assays revealed that overexpression of long noncoding RNA Gm9866 promoted cell proliferation and inhibited apoptosis. These findings thus indicated that long noncoding RNA Gm9866 promoted macrophage polarization and inhibited the nuclear factor-κB signaling pathway. Thus, long noncoding RNA Gm9866 may serve as a potential diagnostic and therapeutic target for polarization-related diseases such as infectious diseases, inflammatory diseases, liver fibrosis, and tumors.

5-Iodotubercidin Inhibits the Growth of Insulinoma Cells by Inducing Apoptosis.

INTRODUCTION: 5-Iodotubercidin, a type of purine derivative, has attracted increasing attention in tumor chemotherapy because of its potential as an antitumor agent in recent years. In this study, we confirmed the effects on apoptosis in insulinoma cell lines induced by 5-iodotubercidin and tried to illuminate the underlying mechanisms. METHODS: We used 5-iodotubercidin in the treatment of insulinoma cells and the cell proliferation was examined using CCK-8 assay, colony-forming assays, and insulinoma animal models. Cell apoptosis was examined using TUNEL assays and Western blotting. Cellular DNA damage was shown by comet assay and immunofluorescence. The expression of apoptosis-regulating proteins and DNA damage biomarker was investigated by Western blotting. Subcutaneous inoculation of the insulinoma cells into nude mice was to measure blood glucose, insulin levels, and tumor growth. ATM siRNA and p53 siRNA were used as loss-of-function targets to evaluate 5-iodotubercidin treatment. RESULTS: 5-Iodotubercidin inhibited the proliferation of insulinoma cells and induced DNA damage and cell apoptosis. Moreover, 5-iodotubercidin induced ATM and p53 activated. In vivo, 5-iodotubercidin inhibited the growth of Ins-1 and Min-6 cells xenografts in nude mice. CONCLUSION: 5-Iodotubercidin induces DNA damage leading to insulinoma cells apoptosis by activating ATM/p53 pathway. Therefore, this is a potential strategy for treating insulinoma.

Imaging manifestations of small cell neuroendocrine carcinoma of the ureter.

Small cell neuroendocrine carcinoma (SCNEC) of the ureter is a rare malignant tumor originating from the metaplasia of urothelial cells. This report presents a case of ureteral SCNEC that was preliminarily disclosed by computed tomography; thereafter, transabdominal ultrasonography, transrectal ultrasonography, and magnetic resonance urography were performed to characterize the mass.

Differential Plasma Proteins Identified via iTRAQ-Based Analysis Serve as Diagnostic Markers of Pancreatic Ductal Adenocarcinoma.

Objective: We aimed to identify differentially expressed proteins in the plasma of patients with pancreatic cancer and control subjects, which could serve as potential tumor biomarkers. Methods: Differentially expressed proteins were determined via isostatic labeling and absolute quantification (iTRAQ). Potential protein biomarkers were identified via enzyme-linked immunosorbent assay (ELISA) in 40 patients and 40 control subjects, and those eventually selected were further validated in 40 pancreatic cancer and normal pancreatic tissues. Results: In total, 30 proteins displayed significant differences in expression among which 21 were downregulated and 9 were upregulated compared with the control group. ELISA revealed downregulation of peroxiredoxin-2 (PRDX2) and upregulation of alpha-1-antitrypsin (AAT), Ras-related protein Rab-2B (RAB2B), insulin-like growth factor-binding protein 2 (IGFBP2), Rho-related GTP-binding protein RhoC (RHOC), and prelamin-A/C (LMNA) proteins in 40 other samples of pancreatic cancer. Notably, only AAT, RAB2B, and IGFBP2 levels were consistent with expression patterns obtained with iTRAQ. Moreover, all three proteins displayed a marked increase in pancreatic cancer tissues. Data from ROC curve analysis indicated that the diagnostic ability of AAT, RAB2B, and IGFBP2 combined with carbohydrate antigen 19-9 (CA19-9) for pancreatic cancer was significantly greater than that of the single indexes (area under the curve (AUC): 90% vs. 75% (CA19-9), 76% (AAT), 71% (RAB2B), and 71% (IGFBP2), all P < 0.01). Conclusion: AAT, RAB2B, and IGFBP2 could serve as effective biomarkers to facilitate the early diagnosis of pancreatic cancer.

HSA-miR-34a-5p regulates the SIRT1/TP53 axis in prostate cancer.

SIRT1 is tightly associated with the progression of prostate cancer while the role of Hsa-miR-34a-5p in SIRT1-mediated prostate cancer is not fully understood. We have thoroughly mined the data from two databases, namely the Lipidemia and the cancer genome atlas (TCGA) and found that SIRT1 was highly expressed in human carcinoma tissues as compared to normal tissues, and patients with high SIRT1 expression level had a shorter survival time. The online tool "Gene-RADAR" was applied to investigate the interaction among SIRT1, the TP53 gene and miR-34a-5p. We found that SIRT1 was up-regulated in cancer tissues from patients diagnosed with prostate and castration-resistant prostate cancer when compared to healthy controls. Pearson analysis indicated a positive correlation between SIRT1 and miR-34a-5p, while data mining on the TargetScan database predicted the binding site between the two. An apoptosis assay of prostate cancer cells (PRAD) confirmed that the overexpression of miR-34a-5p inhibited paclitaxel-induced apoptosis and promoted cell proliferation. Cell cycle analysis verified that miR-34a-5p overexpression blocked PRAD cells in the G2/S phase of the cell cycle. Moreover, the Western blotting (WB) and quantitative PCR (qPCR) assays demonstrated that the overexpression of miR-34a-5p induced down-regulation of the SIRT-related proteins HIF2α and PGC1α, while on the contrary, it up-regulated the expression of two tumour suppressor genes, TP53 and VEGF. In conclusion, we have shown that miR-34a-5p is involved in the oncogenesis of PRAD cells via the SIRT1/TP53 axis.

Establishment of Prognostic Signatures of N6-Methyladenosine-Related lncRNAs and Their Potential Functions in Hepatocellular Carcinoma Patients.

N6-methyladenosine (m6a)-related mRNAs and lncRNAs have been explored for their functions in several cancers. The present study aimed to identify potential signatures of m6a-related lncRNAs in hepatocellular carcinoma (HCC). We downloaded the expression and clinical data from The Cancer Genome Atlas (TCGA) database. The interacted mRNAs and lncRNAs, prognosis-related lncRNAs, potential metabolic pathways of lncRNAs, immune infiltration of various cells, and CD274 (PD-L1) -related lncRNAs were analyzed. Then, in vitro experiments explored the role of AC012073.1 (LOC105377626) in HCC cell lines. We found that candidate 14 lncRNA signatures play functions in HCC maybe by affecting immune infiltration, cell cycle, Notch signaling pathway, etc. LncRNA AC012073.1 (LOC105377626) functions as oncogenic roles in affecting HCC prognosis.

Imaging findings of the primary mucoepidermoid carcinoma of the breast.

Mucoepidermoid carcinoma (MEC) is an invasive tumor that has been reported in many organs, such as the salivary glands, lungs, esophagus, and thymus; however, it rarely affects the breast. Here, we report a case of primary breast MEC with imaging, including mammography, ultrasonography, and magnetic resonance imaging.

Cancer-secreted exosomal miR-21-5p induces angiogenesis and vascular permeability by targeting KRIT1.

Cancer-secreted exosomes are critical mediators of cancer-host crosstalk. In the present study, we showed the delivery of miR-21-5p from colorectal cancer (CRC) cells to endothelial cells via exosomes increased the amount of miR-21-5p in recipient cells. MiR-21-5p suppressed Krev interaction trapped protein 1 (KRIT1) in recipient HUVECs and subsequently activated ß-catenin signaling pathway and increased their downstream targets VEGFa and Ccnd1, which consequently promoted angiogenesis and vascular permeability in CRC. A strong inverse correlation between miR-21-5p and KRIT1 expression levels was observed in CRC-adjacent vessels. Furthermore, miR-21-5p expression in circulating exosomes was markedly higher in CRC patients than in healthy donors. Thus, our data suggest that exosomal miR-21-5p is involved in angiogenesis and vascular permeability in CRC and may be used as a potential new therapeutic target.

SETD4 in the Proliferation, Migration, Angiogenesis, Myogenic Differentiation and Genomic Methylation of Bone Marrow Mesenchymal Stem Cells.

Epigenetic modification is a crucial mechanism affecting the biological function of stem cells. SETD4 is a histone methyltransferase, and its biological role in bone marrow mesenchymal stem cells (BMSCs) is currently unknown. In this study, we employed CRISPR/Cas9 technology edited mouse model and found that SETD4 knockout significantly promoted the proliferation of BMSCs, impaired BMSCs migration and differentiation potentials of lineages of cardiacmyocyte and smooth muscle cell, and even the angiogenesis via paracrine of VEGF. Through Reduced Representation Bisulfite Sequencing (RRBS) method, we verified that the overall genomic methylation of BMSCs in the SETD4 knockout group only was decreased by 0.47 % compared with wild type. However, the changed genomic methylation covers a total of 96,331 differential methylated CpG sites and 8,692 differential methylation regions (DMRs), with part of them settled in promoter regions. Bioinformatic analysis revealed that differential CpG islands and DMRs in promoter impacted 270 GO functions and 34 KEGG signaling pathways, with some closely related to stem cell biology. Mechanismly, SETD4 knockout inhibited sets of monomethylases and dimethylases for histone lysine, along with significant changes in some factors including Nkx2.5, Gata4, Gli2, Grem2, E2f7, Map7, Nr2f2 and Shox2 that associated with stem cell biology. These results are the first to reveal that even though SETD4 changes the genome's overall methylation to a limited extent in BMSCs, it still affects the numerous cellular functions and signaling pathways, implying SETD4-altered genomic methylation serves a crucial molecular role in BMSCs' biological functions.

[Construction and Identification of Acute Myeloid Leukemia NOD/SCID Mouse Model by Tail Vein Injection of THP-1 Cells].

OBJECTIVE: To construct NOD/SCID mouse leukemia model by using THP-1 cells. METHODS: Eighteen female NOD/SCID mice aged 3 to 4 weeks were randomly divided into control group, model group A and model group B (6 in each group). Before inoculation, each mouse was intraperitoneally injected with cyclophosphamide 2 mg/(kg·d) for 2 d, and the mice in model groups were inoculated with cells within 24 h after pretreatment. The mice in model group were inoculated with THP-1 cell suspension in logarithmic growth phase by 1×107 cells/group (group A) and 5×106 cells/group (group B), the mice in the control group were injected with the same amount of normal saline in the tail vein. The general situation was observed, blood routine test and peripheral blood leukocyte classification were performed at 7, 14, 21, 28 d of inoculation before the pre-treatment, and at the time sacrifice. Before dying, tissue of mice were collected and histological examination was performed. RESULTS: Pilereation, droopiness and hypkinesia could be observed from d 7 and d 10 of inoculation cells in model group. Compared with the control group, the body weight of the mice in model group A and B decreased significantly after 21 days of inoculation (P<0.01), and the white blood cell counts increased significantly after 28 days of modeling (P<0.01). Among them, the above-mentioned presentation in inoculation of 1×107 group A was the most significant. Histopathological sections showed diffuse infiltration of leukemia cells in the spleen of the model group. The immunohistochemistry results indicated that the leukemia cells were positive for anti-human CD13, which confirmed the successful establishment of the model. CONCLUSION: After pretreatment with intraperitoneal injection of CTX in NOD/SCID mice, the injection of 1×107 or 5×106 THP-1 cells in tail vein of each mouse can successfully construct an acute myeloid leukemia animal model. The tumor formation is more much faster by injection of high concentration THP-1 cells.