Circ_0036412 affects the proliferation and cell cycle of hepatocellular carcinoma via hedgehog signaling pathway.

BACKGROUND: Hepatocellular carcinoma (HCC), as the most common type of liver cancer, is characterized by high recurrence and metastasis. Circular RNA (circRNA) circ_0036412 was selected for studying the underlying mechanisms of HCC. METHODS: Quantitative real time-polymerase chain reaction (qRT-PCR) and western blot analyzed gene and protein expression. Functional experiments evaluated HCC cell proliferation, apoptosis and cell cycle in vitro. In vivo experiments detected HCC carcinogenesis in vivo. Fluorescence in situ hybridization (FISH) assays evaluated the subcellular distribution. Luciferase reporter, Chromatin immunoprecipitation (ChIP), DNA pulldown, RNA-binding protein immunoprecipitation (RIP), and RNA pulldown assays detected the underlying mechanisms. RESULTS: Circ_0036412 is overexpressed in HCC cells and features circular structure. PRDM1 activates circ_0036412 transcription to regulate the proliferation and cell cycle of HCC cells in vitro. Circ_0036412 modulates Hedgehog pathway. GLI2 propels HCC growth in vivo. Circ_0036412 up-regulates GLI2 expression by competitively binding to miR-579-3p, thus promoting the proliferation and inhibiting cell cycle arrest of HCC cells. Circ_0036412 stabilizes GLI2 expression by recruiting ELAVL1. Circ_0036412 propels the proliferation and inhibits cell cycle arrest of HCC cells in vitro through Hedgehog pathway. CONCLUSIONS: Circ_0036412 affects the proliferation and cell cycle of HCC via Hedgehog signaling pathway. It offers an insight into the targeted therapies of HCC.

Exosomal miR-628-5p from M1 polarized macrophages hinders m6A modification of circFUT8 to suppress hepatocellular carcinoma progression.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. CircFUT8 has been shown to be upregulated in cancers, but its function in HCC remains unclear. Tumor-associated macrophages (TAMs) are one of the main components of the tumor microenvironment (TME), and M1 macrophages function as tumor suppressors in cancers. Exosomes exert an important role in the TME, and circRNAs can be modified by m6A. We investigated the function of circFUT8 in HCC and its interaction with exosomes, M1 macrophages, and m6A. METHODS: CircFUT8 expression was detected in HCC cells, and its effects on HCC cell growth were verified through functional assays. Mechanism assays including RNA pull down, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter assays were undertaken to verify how circFUT8 may interact with miR-628-5p, and how these molecules may modulate HCC cell malignancy via interacting with exosomes and macrophages. RESULTS: CircFUT8 was upregulated in HCC cells and it accelerated HCC cell growth. Exosomes derived from M1 macrophages transferred miR-628-5p to HCC cells to inhibit human methyltransferase-like 14 (METTL14) expression. METTL14 promoted circFUT8 m6A modification and facilitated its nuclear export to the cytoplasm, where M1 macrophages regulated the circFUT8/miR-552-3p/CHMP4B pathway, thereby suppressing HCC progression. CONCLUSION: M1 macrophages-derived exosomal miR-628-5p inhibited the m6A modification of circFUT8, inhibiting HCC development.

Linked Color Imaging Can Improve Detection Rate of Early Gastric Cancer in a High-Risk Population: A Multi-Center Randomized Controlled Clinical Trial.

BACKGROUND: Early diagnosis of gastric cancer is difficult in China due to the lack of a valid method for endoscopic screening. Early gastric cancer, especially flat gastric cancer, lacks specific endoscopic features. Many cases appear to be similar to ordinary gastritis cases under normal white light endoscopy, which can lead to misdiagnosis. AIMS: In order to find a new method to improve detection rate of early gastric cancer in China, we designed a trial to validate linked color imaging (LCI) for screening of early gastric cancer in a high-risk population, as compared to white light imaging (WLI). METHOD: Subjects were randomly allocated to either the LCI + WLI or WLI group and then subjected to gastroscopy and all endoscopies were made after special preparation. All endoscopists had knowledge of this experiment. The main indicator was the rate of detection of gastric neoplastic lesions. The difference in the detection rate between the two groups is reported. RESULTS: The detection rate was 4.31% in the WLI group and 8.01% in the LCI + WLI group. This is a difference of 3.70% with a P value < 0.001 and an OR (95% CI) of 1.934 (1.362, 2.746). The lower limit of the 95% CI was greater than 0, and the superiority margin was 1%. CONCLUSION: The detection rate of gastric neoplastic lesions was higher in the LCI + WLI group than in the WLI group, LCI might be an effective method for screening early gastric cancer.

Circular RNA circRHOT1 promotes hepatocellular carcinoma progression by initiation of NR2F6 expression.

BACKGROUND: Increasing evidence has revealed a close relationship between non-coding RNAs and cancer progression. Circular RNAs (circRNAs), a recently identified new member of non-coding RNAs, are demonstrated to participate in diverse biological processes, such as development, homeostatic maintenance and pathological responses. The functions of circRNAs in cancer have drawn wide attention recently. Until now, the expression patterns and roles of circRNAs in hepatocellular carcinoma (HCC) have remained largely unknown. METHODS: Bioinformatics method was used to screen differentially expressed novel circRNAs in HCC. Northern blotting, qRT-PCR, in situ hybridization (ISH) and RNA-FISH were utilized to analyzed the expression of circRHOT1 in HCC tisues.CCK8, colony formation, EdU assays were used to analyze proliferation of HCC cells. Transwell assay was utilized to analyze HCC cell migration and invasion. FACS was used for apoptosis analysis. Xenograft experiments were used to analyze tumor growth in vivo. Mass spectrum, RNA pulldown, RIP and EMSA was utilized to test the interaction between circRHOT1 and TIP60. RNA-sequencing method was used to analyze the downstream target gene of circRHOT1. RESULTS: We identified circRHOT1 (hsa_circRNA_102034) as a conserved and dramatically upregulated circRNA in HCC tissues. HCC patients displaying high circRHOT1 level possessed poor prognosis. Through in vitro and in vivo experiments, we demonstrated circRHOT1 significantly promoted HCC growth and metastasis. Regarding the mechanism, we conducted a RNA pulldown with a biotin-labeled circRHOT1-specific probe and found that circRHOT1 recruited TIP60 to the NR2F6 promoter and initiated NR2F6 transcription. Moreover, NR2F6 knockout inhibited growth, migration and invasion, whereas rescuing NR2F6 in circRHOT1-knockout HCC cells rescued the proliferation and metastasis abilities of HCC cells. CONCLUSION: Taken together, circRHOT1 inhibits HCC development and progression via recruiting TIP60 to initiate NR2F6 expression, indicating that circRHOT1 and NR2F6 may be potential biomarkers for HCC prognosis.

Cell-Membrane-Coated Metal-Organic Framework Nanocarrier Combining Chemodynamic Therapy for the Inhibition of Hepatocellular Carcinoma Proliferation.

Chemodynamic therapy (CDT) employs hydrogen peroxide (H2O2) within the tumor microenvironment (TME) to initiate the Fenton reaction and catalyze the generation of hydroxyl radicals (·OH) for targeted therapy. Metal ion-based nanomaterials have garnered significant attention as catalysts due to their potent anti-tumor effects. Hypoxia in the TME is often associated with cancer cell development and metastasis, with HIF-1α being a pivotal factor in hypoxia adaptation. In this study, an organic framework called MIL-101 (Fe) was designed and synthesized to facilitate H2O2-induced ·OH production while also serving as a carrier for the HIF-1α inhibitor Acriflavine (ACF). A biomimetic nanomedical drug delivery system named MIL-101/ACF@CCM was constructed by encapsulating liver cancer cell membranes onto the framework. This delivery system utilized the homologous targeting of tumor cell membranes to transport ACF, inhibiting HIF-1α expression, alleviating tumor hypoxia, and catalyzing ·OH production for effective tumor eradication. Both in vivo and in vitro experiments confirmed that combining ACF with chemotherapy achieved remarkable tumor inhibition by enhancing ROS production and suppressing HIF-1α expression.

Case report: Complete response after transcatheter arterial chemoembolization combined with donafenib plus tislelizumab therapy for hepatocellular carcinoma with main trunk portal vein tumor thrombus in a patient coinfected with HIV and HBV.

Background: Coinfection with the human immunodeficiency virus (HIV) and the hepatitis B virus (HBV) occurs in 5-67% of patients with HIV. HIV weakens the human immune system and leads to various tumors. Patients with unresectable hepatocellular carcinoma (HCC) and HIV experience poor treatment efficacy and have a short survival period. Approximately 70% of cases of HCC are diagnosed at advanced stages due to the subtle onset of the disease. As a result, most cases are not suits for curative therapy. Transcatheter arterial chemoembolization (TACE) is the first-line treatment for intermediate-stage HCC and is commonly used to treat unresectable HCC in China. Recent advancements in systemic treatments have significantly enhanced the effectiveness of unresectable HCC treatment. Several previous study showed that combination treatment combination therapy can enhance the efficacy. Notably, studies proposed that TACE combined targeted drugs with immune checkpoint inhibitors results in a high objective response rate and overall survival. However, the novelty of this study lies in its report of a complete response using a triple combination in patients with HIV and HCC with main trunk portal vein tumor thrombus. Case presentation: A 57-year-old woman was diagnosed with HCC with a main trunk portal vein tumor thrombus combined with HIV infection, cirrhosis, and chronic viral hepatitis. She underwent TACE and was administered donafenib and tislelizumab. This triple therapy treatment regimen resulted in a clinical complete response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) based on contrast-enhanced computed tomography. Conclusion: We first used TACE combined with donafenib and tislelizumab for HCC patients with main trunk portal vein tumor thrombus and HIV-HBV coinfection and achieved complete response.

Nomogram for predicting severe abdominal pain after initial conventional transarterial chemoembolisation for hepatocellular carcinoma: a retrospective study.

Transarterial chemoembolisation (TACE) is a standard therapy for hepatocellular carcinoma (HCC). However, adverse events, including abdominal pain, are common. This study aimed to investigate and verify the feasibility of a nomogram model to predict severe abdominal pain after first conventional TACE (cTACE) among patients with HCC. Patients with HCC treated with cTACE between October 28, 2019, and August 5, 2022, at a single centre were enrolled (n = 216). Patients were divided into training and validation cohorts (ratio, 7:3). A visual analogue scale score between 7 and 10 was considered severe abdominal pain. A total of 127 (58.8%) patients complained of severe abdominal pain after first cTACE treatment. The nomogram considered age and tumour number and size. The nomogram demonstrated good discrimination, with a C-index of 0.749 (95% confidence interval [CI], 0.617, 0.881). Further, the C-index in the validation cohort reached 0.728 (95% CI 0.592, 0.864). The calibration curves showed ideal agreement between the prediction and real observations, and the nomogram decision curve analysis performed well. The nomogram model can provide an accurate prediction of severe abdominal pain in patients with HCC after first cTACE, aiding in the personalization of pain management and providing novel insights into hospital nursing.

Hypoxia-induced LncRNA DACT3-AS1 upregulates PKM2 to promote metastasis in hepatocellular carcinoma through the HDAC2/FOXA3 pathway.

Growing evidence has revealed that hypoxia is involved in multiple stages of cancer development. However, there are limited reports on the effects of long noncoding RNAs (lncRNAs) on hepatocellular carcinoma (HCC) progression under hypoxia. The main purposes of this study were to analyze the effect of the novel lncRNA DACT3-AS1 on metastasis in HCC and to elucidate the related molecular mechanism. Bioinformatics tools were employed. RT-qPCR or western blot assays were conducted to detect RNA or protein expression. Clinical samples and in vivo assays were utilized to reveal the role of DACT3-AS1 in HCC. Other mechanism and functional analyses were specifically designed and performed as well. Based on the collected data, this study revealed that HIF-1α transcriptionally activates DACT3-AS1 expression under hypoxia. DACT3-AS1 was verified to promote metastasis in HCC. Mechanistically, DACT3-AS1 promotes the interaction between HDAC2 and FOXA3 to stimulate FOXA3 deacetylation, which consequently downregulates the FOXA3 protein. Furthermore, FOXA3 serves as a transcription factor that can bind to the PKM2 promoter region, thus hindering PKM2 expression. To summarize, this study uncovered that HIF-1α-induced DACT3-AS1 promotes metastasis in HCC and can upregulate PKM2 via the HDAC2/FOXA3 pathway in HCC cells.

Collagenous gastritis in a young Chinese woman: A case report.

BACKGROUND: Collagenous gastritis (CG) is a rare condition whose pathogenesis may be related to immune abnormalities. We report a case of CG from China. CASE SUMMARY: A 24-year-old woman presented with recurrent abdominal distension and discomfort for 3 mo. Upper gastrointestinal endoscopy found diffuse nodular elevation-depression changes in the mucosa of the entire gastric corpus. Endoscopic ultrasound showed predominant involvement of the lamina propria and submucosa, and computed tomography imaging showed mild enhancement of the gastric wall. Pathological histology revealed that the thickness of the subepithelial collagen band was about 40 µm, and the Masson trichrome staining result was positive and the Congo red staining result was negative. This case is consistent with the child-adolescent type of CG. CONCLUSION: Serum pepsinogen I, pepsinogen II, pepsinogen I/II ratio, and gastrin-17 may be potential non-invasive monitoring markers. Currently, treatments for CG vary, and the likely prognosis is unknown. Individual cases of gastric cancer in patients with CG have been reported.

Circ_SMAD4 promotes gastric carcinogenesis by activating wnt/ß-catenin pathway.

OBJECTIVES: Circular RNAs (circRNAs) are essential participants in tumour progression. This study focused on investigating the mechanism of a novel functional circRNA in gastric cancer (GC). METHODS: Gene expression was detected by qRT-PCR or Western blot. Survival curves were generated via Kaplan-Meier method. In vitro and in vivo assays were used to investigate the impact of circ_SMAD4 on GC cell growth and tumorigenesis. Agarose gel electrophoresis assay, RNase R treatment and Sanger sequencing were utilized for confirming the circular structure of circ_SMAD4. Relationship between molecules was monitored by a series of mechanical experiments, as needed. RESULTS: Circ_SMAD4 expression was potentiated in GC. Circ_SMAD4 depletion impeded GC cell growth in vitro and restrained tumorigenesis in vivo. Mechanically, nuclear circ_SMAD4 recruited TCF4 to facilitate CTNNB1 transcription, while cytoplasmic circ_SMAD4 sequestered miR-1276 to prevent the silence of CTNNB1 mRNA, leading to activation of Wnt/ß-catenin pathway. Rescue experiments validated that circ_SMAD4 depended on miR-1276/TCF4-regulated CTNNB1 to elicit accelerating effects on GC cell growth. CONCLUSION: Circ_SMAD4 facilitated GC tumorigenesis by activating CTNNB1-dependent Wnt/ß-catenin pathway. Hopefully, the findings could provide new clues for improving GC prognosis and treatment.

Role of N6-Methyladenosine (m6A) Methylation Regulators in Hepatocellular Carcinoma.

Liver cancer is the fifth most common malignant tumor in terms of incidence and the third leading cause of cancer-related mortality globally. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Although great progress has been made in surgical techniques, hepatic artery chemoembolization, molecular targeting and immunotherapy, the prognosis of liver cancer patients remains very poor. N6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotic cells and regulates various stages of the RNA life cycle. Many studies have reported that the abnormal expression of m6A-related regulators in HCC represent diagnostic and prognostic markers and potential therapeutic targets. In this review, firstly, we introduce the latest research on m6A-related regulators in detail. Next, we summarize the mechanism of each regulator in the pathogenesis and progression of HCC. Finally, we summarize the potential diagnostic, prognostic and therapeutic value of the regulators currently reported in HCC.

Exosome-transferred LINC01559 promotes the progression of gastric cancer via PI3K/AKT signaling pathway.

Increasing evidence indicates that long non-coding RNAs (lncRNAs) are associated with the progression of human cancers. However, the expression level and function of LINC01559 (long intergenic non-protein coding RNA 1559) in gastric cancer (GC) are rarely reported. Here we found that LINC01559 was upregulated in GC tissues based on GEPIA (Gene Expression Profiling Interactive Analysis) and TCGA (The Cancer Genome Atlas) databases. Also, LINC01559 was expressed at a lower level in GC cells than in mesenchymal stem cells (MSCs). In vitro experiments revealed that silencing LINC01559 remarkably hindered GC cell proliferation, migration and stemness. Then, we identified that LINC01559 was transmitted form MSCs to GC cells via the exosomes. Immunofluorescence staining and electron microscope validated the existence of exosomes in GC cells. Mechanistically, LINC01559 sponged miR-1343-3p to upregulate PGK1 (phosphoglycerate kinase 1), therefore activating PI3K/AKT pathway. Moreover, LINC01559 recruited EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) to PTEN (phosphatase and tensin homolog) promoter, inducing the methylation of PTEN promoter and finally resulting in PTEN repression. Of note, LINC01559 targeted both PGK1 and PTEN to promote GC progression by activating PI3K/AKT pathway. Taken together, our study demonstrated that LINC01559 accelerated GC progression via upregulating PGK1 and downregulating PTEN to trigger phosphatidylinositol 3-kinase/AKT serine/threonine kinase (PI3K/AKT) pathway, indicating LINC01559 as a potential biomarker for GC treatment.

Solvent Vapor-Assisted Magnetic Manipulation of Molecular Orientation and Carrier Transport of Semiconducting Polymers.

Effective control of the molecular orientation and the degree of ordering in organic semiconductors is important to achieve high-performance organic electronics. Herein, we have successfully achieved highly oriented films in centimeter scale for a naphthalenedicarboximide-based semiconducting polymer (P(NDI2OD-T2)) by solvent vapor annealing (SVA) of precast films under a high magnetic field (HMF). As revealed by the microstructural studies, the SVA-HMF films exhibit a remarkably higher degree of chain alignment and high morphological uniformity compared to the HMF-guided drop-cast films. Based on the structural evolution of the films with the SVA time, a mechanism is proposed to elucidate the alignment process, which emphasizes that the chain aggregates re-formed in the swollen films trigger magnetic alignment and determine the film order. Compared with the unaligned films, field-effect transistors of the magnetic aligned P(NDI2OD-T2) films have exhibited a 19-fold enhancement of electron mobility and an extraordinarily large mobility anisotropy of 125. Furthermore, a significantly reduced energetic barrier for activated transport is observed on the aligned devices from temperature-variable measurements. The improved performance achieved by the HMF-SVA process has indicated its potential for high-performance organic electronic applications.

Enhanced Spin Transport of Conjugated Polymer in the Semiconductor/Insulating Polymer Blend.

Conjugated polymers are of high potential in the development of spintronic devices. In this paper, we report systematic studies on spin transport properties of a semiconducting polymer PBDTTT-C-T in the permalloy/polymer/Pt trilayer using the spin pumping method. Pure spin current with long spin relaxation time is observed via the inverse spin Hall effect (ISHE) measurements. Furthermore, spin current is also found to propagate through the blend film consisting of a small amount of PBDTTT-C-T in an insulating matrix. The polymer blend exhibits a remarkably enhanced spin relaxation length (56 nm) and carrier mobility compared to pristine PBDTTT-C-T. From film microstructural characterizations, we propose that the enhanced spin/carrier transport properties are attributed to the formation of interlinked nanonetwork comprising of the PBDTTT-C-T chain bundles in the inert matrix to afford efficient intrachain charge conduction pathway. Temperature- dependent ISHE measurements support the spin-orbit coupling dominated spin relaxation mechanism.

miR-296 inhibits proliferation and induces apoptosis by targeting FGFR1 in human hepatocellular carcinoma.

MiR-296 was previously reported to be underexpressed in hepatocellular carcinoma (HCC). However, the clinical value of miR-296 and its function in HCC remain poorly understood. In this study, we found that miR-296 levels are decreased in HCC specimens and cells, and that the underexpression of miR-296 is associated with adverse clinical parameters and poor overall survival rate. In vitro experiments indicate that miR-296 inhibits proliferation, colony formation, and cell cycle progression, and enhances apoptosis in HCC cells. Notably, we found that the fibroblast growth factor receptor 1 (FGFR1) is a downstream target that mediates the functions of miR-296 in HCC. Thus, our findings indicate that miR-296 exerts a tumor suppressive role in HCC and is a potential biomarker and drug-target.

A soluble bis-chelated gold(I) diphosphine compound with strong anticancer activity and low toxicity.

Gold-containing compounds have shown anticancer potential, but their clinical applications have been severely limited by poor stability and high toxicity in vivo. Here, we report a novel soluble bis-chelated gold(I)-diphosphine compound (GC20) with strong anticancer activity and low toxicity. GC20 shows strong antiproliferation potency against a broad spectrum of cancer cell lines including cisplatin-resistant cancer cells (IC50 ≈ 0.5 µM) and significantly reduces tumor growth in several tumor xenografts in mouse models at doses as low as 2 mg/kg. Studies of its mechanism revealed that GC20 specifically inhibits the enzymatic activity of thioredoxin reductase by binding to selenocysteine residue, without targeting other well-known selenol and thiol groups contained in biomolecules. Remarkably, in animal studies GC20 was shown to be well tolerated even at the high dose of 8 mg/kg. Our results strongly suggest that GC20 represents a promising candidate for the development of novel anticancer drugs.