Long noncoding RNAs (lncRNAs) have emerged as important regulators in a variety of human diseases, including cancers. However, the overall biological roles and clinical significance of most lncRNAs in gastric carcinogenesis are not fully understood. We investigated the clinical significance, biological function, and mechanism of LINC01234 in gastric cancer. First, we analyzed LINC01234 alterations in gastric cancerous and noncancerous tissues through an analysis of sequencing data obtained from The Cancer Genome Atlas. Next, we evaluated the effect of LINC01234 on the gastric cancer cell proliferation and apoptosis, and its regulation of miR-204-5p by acting as a competing endogenous RNA (ceRNA). The animal model was used to support the experimental findings. We found that LINC01234 expression was significantly upregulated in gastric cancer tissues and was associated with larger tumor size, advanced TNM stage, lymph node metastasis, and shorter survival time. Furthermore, knockdown of LINC01234-induced apoptosis and growth arrest and inhibited tumorigenesis in mouse xenografts. Mechanistic investigations indicated that LINC01234 functioned as a ceRNA for miR-204-5p, thereby leading to the derepression of its endogenous target core-binding factor β (CBFB). LINC01234 is significantly overexpressed in gastric cancer, and LINC01234-miR-204-5p-CBFB axis plays a critical role in gastric cancer tumorigenesis. Our findings may provide a potential new target for gastric cancer diagnosis and therapy. .

Spexin mRNA and protein are widely expressed in rat tissues and associate with weight loss in rodents of diet-induced obesity. Its location in endocrine and epithelial cells has also been suggested. Spexin is a novel peptide that involves weight loss in rodents of diet-induced obesity. Therefore, we aimed to examine its expression in human tissues and test whether spexin could have a role in glucose and lipid metabolism in type 2 diabetes mellitus (T2DM). The expression of the spexin gene and immunoreactivity in the adrenal gland, skin, stomach, small intestine, liver, thyroid, pancreatic islets, visceral fat, lung, colon, and kidney was higher than that in the muscle and connective tissue. Immunoreactive serum spexin levels were reduced in T2DM patients and correlated with fasting blood glucose (FBG, r=-0.686, P<0.001), hemoglobin A1c (HbA1c, r=-0.632, P<0.001), triglyceride (TG, r=-0.236, P<0.001) and low density lipoprotein-cholesterol (LDL-C, r=-0.382, P<0.001). A negative correlation of blood glucose with spexin was observed during oral glucose tolerance test (OGTT). Spexin is intensely expressed in normal human endocrine and epithelial tissues, indicating that spexin may be involved in physiological functions of endocrine and in several other tissues. Circulating spexin levels are low in T2DM patients and negatively related to blood glucose and lipids suggesting that the peptide may play a role in glucose and lipid metabolism in T2DM.

BackgroundNumerous studies have shown that long non-coding RNAs (lncRNAs) behave as a novel class of transcript during multiple cancer processes, such as cell proliferation, apoptosis, migration, and invasion. LINC00152 is located on chromosome 2p11.2, and has a transcript length of 828 nucleotides. The biological role of LINC00152 in LAD(lung adenocarcinoma) remains unknown.MethodsQuantitative reverse transcription PCR(qRT-PCR) was used to detect LINC00152 expression in 60 human LAD tissues and paired normal tissues. In vitro and in vivo studies showed the biological function of LINC00152 in tumour progression. RNA transcriptome sequencing technology was performed to identify the downstream suppressor IL24(interleukin 24) which was further examined by qRT-PCR, western bolt and rescue experiments. RNA immunoprecipitation (RIP), RNA pulldown, and Chromatin immunoprecipitation (ChIP) assays were carried out to reveal the interaction between LINC00152, EZH2 and IL24.ResultsLINC00152 expression was upregulated in 60 human LAD tissues and paired normal tissues. High levels of LINC00152 expression were correlated with advanced TNM stage, larger tumor size, and lymph node metastasis, as well as shorter survival time. Silencing of LINC00152 suppressed cell growth and induced cell apoptosis. LINC00152 knockdown altered the expression of many downstream genes, including IL24. LINC00152 could interact with EZH2 and inhibit IL24 transcription. Moreover, the ectopic expression of IL24 repressed cell proliferation and partly reversed LINC00152 overexpression-induced promotion of cell growth in LAD.ConclusionsOur study reveals an oncogenic role for LINC00152 in LAD tumorigenesis, suggesting that it could be used as a therapeutic target in LAD treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0581-3) contains supplementary material, which is available to authorized users.

Interacting with proteins is a crucial way for long noncoding RNAs (lncRNAs) to exert their biological responses. Here we report a high throughput strategy to characterize lncRNA interacting proteins in vivo by combining tobramycin affinity purification and mass spectrometric analysis (TOBAP-MS). Using this method, we identify 140 candidate binding proteins for lncRNA highly upregulated in liver cancer (HULC). Intriguingly, HULC directly binds to two glycolytic enzymes, lactate dehydrogenase A (LDHA) and pyruvate kinase M2 (PKM2). Mechanistic study suggests that HULC functions as an adaptor molecule that enhances the binding of LDHA and PKM2 to fibroblast growth factor receptor type 1 (FGFR1), leading to elevated phosphorylation of these two enzymes and consequently promoting glycolysis. This study provides a convenient method to study lncRNA interactome in vivo and reveals a unique mechanism by which HULC promotes Warburg effect by orchestrating the enzymatic activities of glycolytic enzymes.

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Cholangiocarcinoma (CCA) is the most common biliary tract malignancy, with a low survival rate and limited treatment options. Long non-coding RNAs (lncRNAs) have recently been verified to have significant regulatory functions in many kinds of human cancers. It was discovered in this study that the lncRNA PVT1, whose expression is significantly elevated in CCA, could be a molecular marker of CCA. Experiments indicated that PVT1 knockdown greatly inhibited cell migration and proliferation in vitro and in vivo. According to RNA sequencing (RNA-seq) analysis, PVT1 knockdown dramatically influenced target genes associated with cell angiogenesis, cell proliferation, and the apoptotic process. RNA immunoprecipitation (RIP) analysis demonstrated that, by binding to epigenetic modification complexes (PRC2), PVT1 could adjust the histone methylation of the promoter of ANGPTL4 (angiopoietin-like 4) and, thus, promote cell growth, migration, and apoptosis progression. The data verified the significant functions of PVT1 in CCA oncogenesis, and they suggested that PVT1 could be a target for CCA intervention.

Cholangiocarcinoma (CCA) is the as the most frequently observed biliary tract malignancy, which has low survival rate in addition to constrained treatment options; nevertheless, the fundamental molecular phenomenon underlying malignant progression of CCA is quite ambiguous. Recently long non-coding RNAs (lncRNAs) have been found to have significant regulatory functions in several human cancers. Herein, we have figured out that lncRNA SNHG1, with substantially enhanced expression in CCA, is capable of acting as the oncogenic molecule of CCA. As revealed by our data, SNHG1 knockdown extensively inhibited CCA cell migration as well as proliferation in vitro and in vivo. In addition, in accordance with the findings of the RNA-Seq analysis, SNHG1 knockdown exhibited a significant impact on the target genes that were linked to cell migration and regulation of cell proliferation, in addition to the apoptotic phenomenon. In a mechanistic manner, we also showed that SNHG1 bound to the histone methyltransferase enhancer of the zeste homolog 2 (EZH2, which is regarded as the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is an extremely conserved protein complex regulating gene expression with the help of methylating lysine 27 on histone H3), specifying the histone alteration pattern on the target genes, including CDKN1A, and, as a result, altered the CCA cell biology. These data verified a major function of the epigenetic regulation of SNHG1 in CCA oncogenesis, in addition to its likely function as a target for CCA interruption.

Gluconeogenesis is drastically increased in patients with type 2 diabetes and accounts for increased fasting plasma glucose concentrations. Circulating levels of prostaglandin (PG) F are also markedly elevated in diabetes; however, whether and how PGF regulates hepatic glucose metabolism remain unknown. Here, we demonstrated that PGF receptor (F-prostanoid receptor [FP]) was upregulated in the livers of mice upon fasting- and diabetic stress. Hepatic deletion of the FP receptor suppressed fasting-induced hepatic gluconeogenesis, whereas FP overexpression enhanced hepatic gluconeogenesis in mice. FP activation promoted the expression of gluconeogenic enzymes (PEPCK and glucose-6-phosphatase) in hepatocytes in a FOXO1-dependent manner. Additionally, FP coupled with G in hepatocytes to elicit Ca release, which activated Ca/calmodulin-activated protein kinase IIγ (CaMKIIγ) to increase FOXO1 phosphorylation and subsequently accelerate its nuclear translocation. Blockage of p38 disrupted CaMKIIγ-induced FOXO1 nuclear translocation and abrogated FP-mediated hepatic gluconeogenesis in mice. Moreover, knockdown of hepatic FP receptor improved insulin sensitivity and glucose homeostasis in / mice. FP-mediated hepatic gluconeogenesis via the CaMKIIγ/p38/FOXO1 signaling pathway, indicating that the FP receptor might be a promising therapeutic target for type 2 diabetes.