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.

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.

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.

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.

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.

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.

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.