Identifying survival-associated modules from the dysregulated triplet network in glioblastoma multiforme.

BACKGROUND: Long noncoding RNAs (lncRNAs) can act as competitive endogenous RNAs (ceRNAs) to compete with mRNAs for binding miroRNAs (miRNAs). The dysregulated triplets, composed by mRNAs, lncRNAs, and miRNAs, contributed to the development and progression of diseases, such as cancer. However, the roles played by triplet biomarkers are not fully understand in glioblastoma multiforme (GBM) patient survival. OBJECTIVES: Here, we constructed a differential triplet interaction network (TriNet) between GBM and normal tissues and identified GBM survival related triplets. METHODS: Four significantly dysregulated modules, enriched differentially expressed molecules, were identified by integrating affinity propagation method and hypergeometric method. Furthermore, knockdown of TP73-AS1 was implemented by siRNA and the expression of RFX1 was examined in U87 cells by qRT-PCR. The apoptosis of U87 cells was investigated using MTT assay and Acridine orange/Ethidium bromide (AO/EB) assay. RESULTS: We randomly split GBM samples into training and testing sets, and found that these four modules can robustly and significantly distinguish low- and high-survival patients in both two sets. By manually curated literatures for triplets mediated by core interactions, we found that members involved tumor invasion, proliferation, and migration. The dysregulated triplets may cause the poor survival of GBM patients. We finally experimentally verified that knockdown of TP73-AS1, an lncRNA of one triplet, could not only reduce the expression of RFX1, an mRNA of this triplet, but also induce apoptosis in U87 cells. CONCLUSIONS: These results can provide further insights to understand the functions of triplet biomarkers that associated with GBM prognosis.

S100B and ADMA in cerebral small vessel disease and cognitive dysfunction.

BACKGROUND: Glial cell activation and endothelial dysfunction are thought to contribute to the pathophysiology of cerebral small vessel disease (SVD). The purpose of the present study was to determine if levels of S100B, a protein highly expressed in glial cells, and asymmetric dimethylarginine (ADMA), which promotes endothelial dysfunction, are elevated in the serum of patients with SVD and correlate with their cognitive functioning. METHODS: The serum levels of S100B and ADMA were measured with enzyme-linked immunosorbent assays in 210 patients with SVD and 207 controls. Cognitive functioning was evaluated using the Montreal Cognitive Assessment. SVD lesions were categorized as isolated lacunar infarcts (ILI), multiple lacunar infarcts, leukoaraiosis (LA), and LA with cerebral atrophy using magnetic resonance imaging. RESULTS: SVD patients were significantly older, and more likely to have hypertension, diabetes, and heart disease, and smoke compared to controls (Ps<0.05). Plasma levels of S100B and ADMA were significantly higher in SVD patients (Ps<0.05), though only S100B was significant after adjusting for the confounding factors. Subtype analyses indicated that ADMA levels were differentially altered depending on lesion type, particularly in cases with ILI and LA (Ps<0.05). Compared with controls, SVD patients had significant cognitive impairment that was most profound in the cases with LA (all Ps<0.05). Levels of S100B and ADMA were significantly correlated with cognitive decline in patients with LA (P<0.05). CONCLUSION: S100B and ADMA are elevated in SVD, and are associated with cognitive impairment in patients with LA lesions.