Epstein–Barr virus noncoding RNAs from the extracellular vesicles of nasopharyngeal carcinoma (NPC) cells promote angiogenesis via TLR3/RIG-I-mediated VCAM-1 expression

Viral noncoding RNAs (Epstein–Barr virus-encoded RNAs, EBERs) are believed to play a critical role in the progression of lymphoma and nasopharyngeal carcinoma (NPC). However, the accurate mechanisms accounting for their oncogenic function have not been elucidated, especially in terms of interaction between tumor cells and mesenchymal cells. Here, we report that, in addition to NPC cells, EBERs are also found in endothelial cells in Epstein–Barr virus (EBV)-infected NPC parenchymal tissues, which implicates NPC-derived extracellular vesicles (EVs) in transmitting EBERs to endothelial cells. In support of this hypothesis, we first ascertained if EBERs could be transferred to endothelial cells via EVs isolated from NPC culture supernatant. Then, we clarified that EVs-derived EBERs could promote angiogenesis through stimulation of VCAM-1 expression. Finally, we explored the involvement of EBER recognition by TLR3 and RIG-I in NPC angiogenesis. Our observations collectively illustrate the significance and mechanism of EVs-derived EBERs in angiogenesis and underlie the interaction mechanisms between EBV-infected NPC cells and the tumor microenvironment.     

The nucleolar detention pathway: A cellular strategy for regulating molecular networks

Molecular dynamics ensures that proteins and other factors reach their site of action in a timely and efficient manner. This is essential to the formation of molecular complexes, as they require an ever-changing framework of specific interactions to facilitate a model of self-assembly. Therefore, the absence or reduced availability of any key component would significantly impair complex formation and disrupt all downstream molecular networks. Recently, we identified a regulatory mechanism that modulates protein mobility through the inducible expression of a novel family of long noncoding RNA. In response to diverse environmental stimuli, the nucleolar detention pathway (NoDP) captures and immobilizes essential cellular factors within the nucleolus away from their effector molecules. The vast array of putative NoDP targets, including DNA (cytosine-5)-methyltransferase 1 (DNMT1) and the delta catalytic subunit of DNA polymerase (POLD1), suggests that this may be a common and significant regulatory mechanism. Here, we discuss the implications of this new posttranslational strategy for regulating molecular networks.     

Aplysia hemolymph promotes neurite outgrowth and synaptogenesis of identifiedHelix neurons in cell culture

Hemolymph of adultAplysia californica significantly affects neurite outgrowth of identified neurons of the land snailHelix pomatia. The metacerebral giant cell (MGC) and the motoneuron C3 from the cerebral ganglion and the neuron B2 from the buccal ganglion ofH. pomatia were isolated by enzymatic and mechanical dissociation and plated onto poly-l-lysine-coated dishes either containing culture medium conditioned byHelix ganglia, or pre-treated withAplysia hemolymph. To determine the extent of neuronal growth we measured the neurite elongation and the neuritic field of cultured neurons at different time points.Aplysia hemolymph enhances the extent and rate of linear outgrowth and the branching domain ofHelix neurons. With the hemolymph treatment the MGC neuron more consistently forms specific chemical synapses with its follower cell B2, and these connections are more effective than those established in the presence of the conditioned medium.     

RNA templating of molecular assembly and covalent modification patterning in early molecular evolution and modern biosystems

The Direct RNA Template (DRT) hypothesis proposes that an early stage of genetic code evolution involved RNA molecules acting as stereochemical recognition templates for assembly of specific amino acids in sequence-ordered arrays, providing a framework for directed covalent peptide bond formation. It is hypothesized here that modern biological precedents may exist for RNA-based structural templating with functional analogies to hypothetical DRT systems. Beyond covalent molecular assembly, an extension of the DRT concept can include RNA molecules acting as dynamic structural template guides for the specific non-covalent assembly of multi-subunit complexes, equivalent to structural assembly chaperones. However, despite numerous precedents for RNA molecules acting as scaffolds for protein complexes, true RNA-mediated assembly chaperoning appears to be absent in modern biosystems. Another level of function with parallels to a DRT system is possible if RNA structural motifs dynamically guided specific patterns of catalytic modifications within multiple target sites in a pre-formed polymer or macromolecular complex. It is suggested that this type of structural RNA templating could logically play a functional role in certain areas of biology, one of which is the glycome of complex organisms. If any such RNA templating processes are shown to exist, they would share no necessary evolutionary relationships with events during early molecular evolution, but may promote understanding of the practical limits of biological RNA functions now and in the ancient RNA World. Awareness of these formal possibilities may also assist in the current search for functions of extensive non-coding RNAs in complex organisms, or for efforts towards artificial rendering of DRT systems.     

A prognostic five long–noncoding RNA signature for patients with rectal cancer

This study aimed to identify prognostic long noncoding RNAs (lncRNAs) signature for predicting the prognosis of patients with rectal cancer. LncRNA-sequencing data and clinicopathological data of patients with rectal cancer were retrieved from The Cancer Genome Atlas database. Univariate and multivariate Cox proportional hazards regression analysis, the least absolute shrinkage, and selection operator analysis and the Kaplan-Meier curve method were employed to identify prognostic lncRNAs and construct multi-lncRNA signature. Finally, five lncRNAs (AC079789.1, AC106900.2, AL121987.1, AP004609.1, and LINC02163) were identified to construct a five-lncRNA signature. According to the five-lncRNA signature, patients with rectal cancer were divided into a high-risk group and low-risk group. Patients with rectal cancer had significantly poorer overall survival in the high-risk group than in the low-risk group. We used a time-dependent receiver operating characteristic curve to assess the power of the five-lncRNA signature by calculating the area under the curve (AUC). The AUCs for predicting 3-year survival and 5-year survival were 0.742 and 0.935, respectively, which indicated a good performance of the five-lncRNA signature. The five-lncRNA signature was independently associated with the prognosis of patients with rectal cancer through using univariate and multivariate Cox regression analysis. The biological function of the five lncRNAs was enriched in some cancer-related biological processes and pathways by performing functional enrichment analysis of their correlated protein-coding genes. In conclusion, we developed a five-lncRNA signature as a potential indicator for rectal cancer.