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.

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.

Multiple m6A RNA methylation modulators promote the malignant progression of hepatocellular carcinoma and affect its clinical prognosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world. N6-methyladenosine (m6A) RNA methylation is dynamically regulated by m6A RNA methylation modulators ("writer," "eraser," and "reader" proteins), which are associated with cancer occurrence and development. The purpose of this study was to explore the relationships between m6A RNA methylation modulators and HCC. METHODS: First, using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we compared the expression levels of 13 major m6A RNA methylation modulators between HCC and normal tissues. Second, we applied consensus clustering to the expression data on the m6A RNA methylation modulators to divide the HCC tissues into two subgroups (clusters 1 and 2), and we compared the clusters in terms of overall survival (OS), World Health Organization (WHO) stage, and pathological grade. Third, using least absolute shrinkage and selection operator (LASSO) regression, we constructed a risk signature involving the m6A RNA methylation modulators that affected OS in TCGA and ICGC analyses. RESULTS: We found that the expression levels of 12 major m6A RNA methylation modulators were significantly different between HCC and normal tissues. After dividing the HCC tissues into clusters 1 and 2, we found that cluster 2 had poorer OS, higher WHO stage, and higher pathological grade. Four m6A RNA methylation modulators (YTHDF1, YTHDF2, METTL3, and KIAA1429) affecting OS in the TCGA and ICGC analyses were selected to construct a risk signature, which was significantly associated with WHO stage and was also an independent prognostic marker of OS. CONCLUSIONS: In summary, m6A RNA methylation modulators are key participants in the malignant progression of HCC and have potential value in prognostication and treatment decisions.

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.

Paired box 8 suppresses tumor angiogenesis and metastasis in gastric cancer through repression of FOXM1 via induction of microRNA-612.

BACKGROUND: Paired box 8 (PAX8) has been documented to be downregulated in gastric cancer. However, its biological function in this malignancy is poorly understood. METHODS: In the present work, we investigated the effects of PAX8 overexpression and knockdown on the aggressive phenotype of gastric cancer cells. We further checked the involvement of forkhead box M1 (FOXM1), a ubiquitously expressed oncogene that can facilitate gastric cancer progression, in the action of PAX8. RESULTS: Ectopic expression of PAX8 blocked the migration and invasion of both AGS and SGC-7901 cells, but had no effect on cell proliferation. Conversely, knockdown of PAX8 enhanced gastric cancer cell migration and invasion. PAX8 overexpression inhibited epithelial-mesenchymal transition (EMT) and pro-angiogenic activity of gastric cancer cells. Mechanistically, PAX8 overexpression downregulated FOXM1 by stimulating microRNA (miR)-612 expression. Ectopic expression of miR-612 recapitulated the effect of PAX8 overexpression on gastric cancer cells, causing an inhibition of migration, invasion, EMT, and angiogenesis. Knockdown of miR-612 or overexpression of FOXM1 significantly reversed the tumor-suppressive activity of PAX8. In vivo studies further demonstrated that PAX8 overexpression restrained tumor angiogenesis and metastasis in nude mice, which was accompanied by increased expression of miR-612 and decreased expression of FOXM1. CONCLUSIONS: PAX8 exerts a tumor-suppressive effect against gastric cancer cells, largely through induction of miR-612 and repression of FOXM1. Therefore, restoration of PAX8 expression may offer therapeutic benefits in the treatment of gastric cancer.

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.