Long non-coding RNA (lncRNA) is emerging as an critical regulator in multiple cancers, including pancreatic cancer (PC). Recently, lncRNA SNHG15 was found to be up-regulated in gastric cancer and hepatocellular carcinoma, exerting oncogenic effects. Nevertheless, the biological function and regulatory mechanism of SNHG15 remain unclear in pancreatic cancer (PC). In this study, we reported that SNHG15 expression was also upregulated in PC tissues, and its overexpression was remarkably associated with tumor size, tumor node metastasis (TNM) stage and lymph node metastasis in patients with PC. SNHG15 knockdown inhibited proliferative capacities and suppressed apoptotic rate of PC cells in vitro, and impaired in-vivo tumorigenicity. Additionally, RNA immunoprecipitation (RIP) assays showed that SNHG15 epigenetically repressed the P15 and Kruppel-like factor 2 (KLF2) expression via binding to enhancer of zeste homolog 2 (EZH2), and chromatin immunoprecipitation assays (CHIP) assays demonstrated that EZH2 was capable of binding to promoter regions of P15 and KLF2 to induce histone H3 lysine 27 trimethylation (H3K27me3). Furthermore, rescue experiments indicated that SNHG15 oncogenic function partially involved P15 and KLF2 repression. Consistently, an inverse correlation between the expression of SNHG15 and traget genes were found in PC tissues. Our results reported that SNHG15 could act as an oncogene in PC, revealing its potential value as a biomarker for early detection and individualized therapy.
Neurodevelopmental biology, coupled with the application of advanced histological, imaging, molecular, cellular, biochemical, and genetic approaches, has provided new insights into these intricate genetic, cellular, and molecular events. During telencephalic development, specific neural progenitor cells (NPCs) proliferate, differentiate into numerous cell types, migrate to their apposite positions, and form an integrated circuitry. Critical disturbance to this dynamic process via genetic and environmental risk can cause neurological disorders and disability. The phosphatidylinositol-3-OH kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling cascade contributes to mediate various cellular processes, including cell proliferation and growth, and nutrient uptake. In light of its critical function, dysregulation of this node has been regarded as a root cause of several neurodevelopmental diseases, such as megalencephaly (“big brain”), microcephaly (“small brain”), autism spectrum disorders, intellectual disability, schizophrenia, and epilepsy. In this review, particular emphasis will be given to the PI3K-Akt-mTOR signaling pathway and their paramount importance in neurodevelopment of the cerebral neocortex, because of its critical roles in complex cognition, emotional regulation, language, and behaviors.
Long non-coding RNAs (lncRNAs) are a group of non-coding RNAs (ncRNAs) >200 nucleotides in length that govern diverse biological processes. Recent evidence suggests that lncRNAs are involved in cancer cell proliferation, apoptosis, invasion, migration, and metastasis. Dysregulation of lncRNAs has been observed in various tumors, and lncRNAs act as oncogenes or tumor suppressors in these malignancies. It has been revealed that lncRNA highly upregulated in liver cancer (HULC) is tightly correlated with a number of cancers such as hepatocellular carcinoma, gastric cancer, colorectal cancer, osteosarcoma, and diffuse large B-cell lymphoma. Depletion of HULC suppressed cancer cell proliferation, migration, and invasion and induced apoptosis. Additionally, HULC may function as a diagnostic biomarker and prognostic indicator for some tumors. In this review, we summarize the current knowledge of the role of HULC in cancer progression and the clinical management of human cancers.
Copper is an essential element in human beings, alterations in serum copper levels could potentially have effect on human health. To date, no data are available regarding how serum copper affects cardiovascular disease (CVD) risk factors in children and adolescents. We examined the association between serum copper levels and CVD risk factors in children and adolescents. We analyzed data consisting of 1427 subjects from a nationally representative sample of the US population in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. The CVD risk factors included total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, fasting glucose, glycohemoglobin, fasting insulin, and blood pressure. Multivariate and generalized linear regressions were performed to investigate associations adjusted for age, gender, ethnicity, poverty:income ratio (PIR), BMI, energy intake, and physical activity. We found significant associations between serum copper and total cholesterol (coefficient = 0.132; 95% CI 0.081, 0.182; P for trend < 0.001), glycohemoglobin (coefficient = 0.044; 95% CI 0.020, 0.069; P < 0.001), and fasting insulin (coefficient = 0.730; 95% CI 0.410, 1.050; P < 0.001) among the included participants. Moreover, in the generalized linear models, subjects with the highest copper levels demonstrated a 0.83% (95% CI 0.44%, 1.24%) greater increase in serum total cholesterol (p for trend < 0.001) when compared to participants with the lowest copper concentrations. Our results provide the first epidemiological evidence that serum copper concentrations are associated with total cholesterol concentrations in children and adolescents. However, the underlying mechanisms still need further exploration.
Musculoskeletal disorders are a group of conditions that affect the motor system, including bones, muscles, tendons, ligaments and joints. 1 People with multiple disorders are particularly vulnerable, especially in the context of an ageing population. Musculoskeletal disorders include a variety of conditions such as osteoarthritis (OA), rheumatoid arthritis (RA), osteopenia, osteoporosis, fractures, sarcopenia, etc. 2 Non-protein-coding RNA makes up 98% of the whole human genome. 3,4 These functional RNAs can be divided into two groups according to the threshold of 200 nucleotides (NTS): small and long non-coding RNAs (lncRNAs). 5,6 LncRNAs regulate the activities of both nearby and distant genes by multiple mechanisms. It could act as a scaffold for transcription factors and other molecules involved in transcription initiation. 7 Moreover, it could serve as protein and microRNA decoys to interfere with cell division by regulating a series of key genes. 8 For those mainly located in the cytoplasm, it could directly target mRNA and induce translation. 9 Currently, an increased number of lncRNAs are found to be involved in the regulation of development and homeostasis of skeletal muscle system. 10,11 It is notable that lncRNAs take key roles in musculoskeletal disorders.
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