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Abstract Background The linear long non-coding RNA P14AS has previously been reported to be dysregulated in colon cancer, but the mechanistic role that P14AS plays in colon cancer progression has yet to be clarified. Accordingly, this study was developed to explore the regulatory functions of ANRIL linear transcript-P14AS in cancer. Methods The expression of P14AS, ANRIL, miR-23a-5p and their target genes were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell supernatants of IL6 and IL8 were measured by Enzyme linked immunosorbent (ELISA) assay. Dual-luciferase reporter assays, RNA immunoprecipitation, or pull-down assays were used to confirm the target association between miR-23a-5p and P14AS or UBE2D3. Cell proliferation and chemosensitivity of NF-κB inhibitor BAY 11-7085 were evaluated by cell counting kit 8 (CCK8). Results When P14AS was overexpressed in colon cancer cell lines, enhanced TNF-NF-κB signaling pathway activity was observed together with increases in IL6 and IL8 expression. The Pita, miRanda, and RNA hybrid databases revealed the ability of miR-23a-5p to interact with P14AS, while UBE2D3 was further identified as a miR-23a-5p target gene. The results of dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation experiments confirmed these direct interactions among P14AS/miR-23a-5p/UBE2D3. The degradation of IκBa mediated by UBE2D3 may contribute to enhanced NF-κB signaling in these cells. Moreover, the beneficial impact of P14AS on colon cancer cell growth was eliminated when cells were treated with miR-23a-5p inhibitors or UBE2D3 was silenced. As such, these findings strongly supported a role for the UBE2D3/IκBa/NF-κB signaling axis as a mediator of the ability of P14AS to promote colon cancer progression. Conclusions These data suggested a mechanism through which the linear ANRIL transcript P14AS can promote inflammation and colon cancer progression through the sequestration of miR-23a-5p and the modulation of NF-κB signaling activity, thus highlighting P14AS as a promising target for therapeutic intervention efforts.

Topologically protected edge channels show prospects for quantum devices. They have been found experimentally in two-dimensional quantum spin Hall insulators (QSHIs), weak topological insulators, and higher-order topological insulators, but the number of materials realizing these topologies is still quite limited. Here, we provide evidence for topological edge states within a novel topology named three-dimensional QSHIs. Its topology originates solely from a nonzero S_{z} spin Chern number for each k_{z} plane of the crystal and is realized in bulk α-Bi_{4}I_{4} with trivial symmetry indicators, as we show by density-functional-theory calculations. We experimentally observe the related edge states at each type of monolayer and bilayer step of this material by scanning tunneling microscopy. Consistently, the edge states are neither interrupted nor backscattered by defects at the step edges corroborating their helical character as expected from the nontrivial topology. Furthermore, two individual edge channels are directly observed at bilayer steps without visible interaction gap opening, demonstrating the robustness of these edge modes against vertical stacking. Our results establish α-Bi_{4}I_{4} as the first material realization of a 3D QSHI whose definition goes beyond the scope of topological symmetry indicators, and provide a pathway for realizing nearly quantized spin Hall conductivity per unit cell in a bulk crystal.

Background: It is well known that P16INK4A, P14ARF, P15INK4B mRNAs, and ANRIL lncRNA are transcribed from the CDKN2A/2B locus. LncRNA P14AS is a lncRNA transcribed from antisense strand of P14ARF promoter to intron-1. Our previous study showed that P14AS could upregulate the expression level of ANRIL and P16INK4A and promote the proliferation of cancer cells. Because polycomb group protein CBX7 could repress P16INK4A expression and bind ANRIL, we wonder whether the P14AS-upregulated ANRIL and P16INK4A expression is mediated with CBX7.Results: In this study, we found that the upregulation of P16INK4A, P14ARF, P15INK4B and ANRIL expression was induced by P14AS overexpression only in HEK293T and HCT116 cells with active endogenous CBX7 expression, but not in MGC803 and HepG2 cells with weak CBX7 expression. Further studies showed that the stable shRNA-knockdown of CBX7 expression abolished the P14AS-induced upregulation of these P14AS target genes in HEK293T and HCT116 cells whereas enforced CBX7 overexpression enabled P14AS to upregulate expression of these target genes in MGC803 and HepG2 cells. Moreover, a significant association between the expression levels of P14AS and its target genes were observed only in human colon cancer tissue samples with high level of CBX7 expression (n = 38, p < 0.05), but not in samples (n = 37) with low level of CBX7 expression, nor in paired surgical margin tissues. In addition, the results of RNA immunoprecipitation (RIP)- and chromatin immunoprecipitation (ChIP)-PCR analyses revealed that lncRNA P14AS could competitively bind to CBX7 protein which prevented the bindings of CBX7 to both lncRNA ANRIL and the promoters of P16INK4A, P14ARF and P15INK4B genes. The amounts of repressive histone modification H3K9m3 was also significantly decreased at the promoters of these genes by P14AS in CBX7 actively expressing cells.Conclusions: CBX7 expression is essential for P14AS to upregulate the expression of P16INK4A, P14ARF, P15INK4B and ANRIL genes in the CDKN2A/2Blocus. P14AS may upregulate these genes’ expression through competitively blocking CBX7-binding to ANRIL lncRNA and target gene promoters.

Spiking neural network (SNN) has emerged as one of the most powerful brain-inspired computing paradigms in complex pattern recognition tasks that can be enabled by neuromorphic hardware. However, owing to the fundamental architecture mismatch between biological and Boolean logic, CMOS implementation of SNN is energy inefficient. A low-power approach with novel “neuro-mimetic” devices offering a direct mapping to synaptic and neuronal functionalities is still an open area. In this paper, SNN constructed with novel magnetic skyrmion-based leaky-integrate-fire (LIF) spiking neuron and the skyrmionic synapse crossbar is proposed. We perform a systematic device-circuit-architecture co-design for pattern recognition to evaluate the feasibility of our proposal. The simulation results demonstrated that our device has superior lower switching voltage and high energy efficiency, two times lower programming energy efficiency in comparison with CMOS devices. This work paves a novel pathway for low-power hardware design using full-skyrmion SNN architecture, as well as promising avenues for implementing neuromorphic computing schemes.