Neuroblastoma is an embryonal tumor of the sympathetic nervous system and the most common extracranial tumor of childhood. By sequencing transcriptomes of low- and high-risk neuroblastomas, we ...detected differentially expressed annotated and nonannotated long noncoding RNAs (lncRNAs). We identified a lncRNA neuroblastoma associated transcript-1 (NBAT-1) as a biomarker significantly predicting clinical outcome of neuroblastoma. CpG methylation and a high-risk neuroblastoma associated SNP on chromosome 6p22 functionally contribute to NBAT-1 differential expression. Loss of NBAT-1 increases cellular proliferation and invasion. It controls these processes via epigenetic silencing of target genes. NBAT-1 loss affects neuronal differentiation through activation of the neuronal-specific transcription factor NRSF/REST. Thus, loss of NBAT-1 contributes to aggressive neuroblastoma by increasing proliferation and impairing differentiation of neuronal precursors.
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•Characterization of long noncoding RNA transcriptome of neuroblastoma tumors•NBAT-1 is a biomarker for predicting the clinical outcome of the neuroblastomas•NBAT-1 epigenetically regulates cell proliferation and migration pathways•NBAT-1 is required for neuronal lineage commitment
Pandey et al. identify the long noncoding RNA NBAT-1 as a prognostic biomarker in neuroblastoma through transcriptome sequencing. NBAT-1 loss increases proliferation and impairs differentiation of neuronal precursors leading to more aggressive disease.
The regulatory nature of long non-coding RNAs (lncRNAs) has been well established in various processes of cellular growth, development, and differentiation. Therefore, it is vital to examine their ...contribution to cancer development. There are ample examples of lncRNAs whose cellular levels are significantly associated with clinical outcomes. However, whether these non-coding molecules can work as either key drivers or barriers to cancer development remains unknown. The current review aims to discuss some well-characterised lncRNAs in the process of oncogenesis and extrapolate the extent of their decisive contribution to tumour development. We ask if these lncRNAs can independently initiate neoplastic lesions or they always need the modulation of well characterized oncogenes or tumour suppressors to exert their functional properties. Finally, we discuss the emerging genetic approaches and appropriate animal and humanised models that can significantly contribute to the functional dissection of lncRNAs in cancer development and progression.
Noncoding RNA (ncRNA) constitutes a significant portion of the mammalian transcriptome. Emerging evidence suggests that it regulates gene expression in cis or trans by modulating the chromatin ...structure. To uncover the functional role of ncRNA in chromatin organization, we deep sequenced chromatin-associated RNAs (CARs) from human fibroblast (HF) cells. This resulted in the identification of 141 intronic regions and 74 intergenic regions harboring CARs. The intronic and intergenic CARs show significant conservation across 44 species of placental mammals. Functional characterization of one of the intergenic CARs, Intergenic10, revealed that it regulates gene expression of neighboring genes through modulating the chromatin structure in cis. Our data suggest that ncRNA is an integral component of chromatin and that it may regulate various biological functions through fine-tuning of the chromatin architecture.
We have generated mouse models of malignant mesothelioma (MM) based upon disruption of the Bap1, Nf2, and Cdkn2ab tumor suppressor loci in various combinations as also frequently observed in human ...MM. Inactivation of all three loci in the mesothelial lining of the thoracic cavity leads to a highly aggressive MM that recapitulates the histological features and gene expression profile observed in human patients. The tumors also show a similar inflammatory phenotype. Bap1 deletion alone does not cause MM but dramatically accelerates MM development when combined with Nf2 and Cdkn2ab (hereafter BNC) disruption. The accelerated tumor development is accompanied by increased Polycomb repression and EZH2-mediated redistribution of H3K27me3 toward promoter sites with concomitant activation of PI3K and MAPK pathways. Treatment of BNC tumor-bearing mice with cisplatin and pemetrexed, the current frontline treatment, prolongs survival. This makes the autochthonous mouse model described here very well suited to explore the pathogenesis of MM and validate new treatment regimens for MM, including immunotherapy.
Unmanned aerial vehicles (UAVs) have been instrumental in enabling many new applications and services, including military and rescue operations, aerial surveillance, civilian applications, precision ...farming, as well as providing extensive wireless network access in remote areas. They have also been used in other areas such as transmission line and oil rig monitoring, disaster recovery, etc. With their increasing payload ability and flight duration, using UAVs is a preferred choice for a multitude of upcoming wireless communication systems. However, because of their open operational nature, UAVs are highly vulnerable to severe security breaches via cyber attacks, eavesdropping on navigational and communication links, etc. Given their widespread applications, the requirement of secured UAV communications has become more and more critical since security failures can lead to detrimental consequences. Several works have examined the extent of privacy and security issues in UAV-assisted networks and introduced various mitigation techniques to address different security challenges. In this paper, a comprehensive survey is conducted that centers on the security issues related to UAV-aided networks. A descriptive taxonomy of various security intrusions on the UAV networks and commonly-used secrecy performance metrics are thoroughly reviewed. An in-depth discussion is provided on alleviating threats with proactive security techniques blended with key wireless communication technologies such as mmWave, non-orthogonal multiple access (NOMA), massive multiple-input multiple-output (MIMO), and cognitive radio. Moreover, several emerging topics like machine learning, software-defined networks, fog and edge computing, blockchain, are discussed in the context of UAV-aided secure communications.
Establishment of silencing by noncoding RNAs (ncRNAs) via targeting of chromatin remodelers is relatively well investigated; however, their role in the maintenance of silencing is poorly understood. ...Here, we explored the functional role of the long ncRNA Kcnq1ot1 in the maintenance of transcriptional gene silencing in the one mega-base Kcnq1 imprinted domain in a transgenic mouse model. By conditionally deleting the Kcnq1ot1 ncRNA at different stages of mouse development, we suggest that Kcnq1ot1 ncRNA is required for the maintenance of the silencing of ubiquitously imprinted genes (UIGs) at all developmental stages. In addition, Kcnq1ot1 ncRNA is also involved in guiding and maintaining the CpG methylation at somatic differentially methylated regions flanking the UIGs, which is a hitherto unknown role for a long ncRNA. On the other hand, silencing of some of the placental-specific imprinted genes (PIGs) is maintained independently of Kcnq1ot1 ncRNA. Interestingly, the non-imprinted genes (NIGs) that escape RNA-mediated silencing are enriched with enhancer-specific modifications. Taken together, this study illustrates the gene-specific maintenance mechanisms operational at the Kcnq1 locus for tissue-specific transcriptional gene silencing and activation.
The present experimental investigation aims to analyse the effect of various machining parameters, such as pulse peak current (Ion), pulse on time (Ton), pulse off time (Toff) and spark voltage (SV) ...on the surface roughness (SR) and material removal rate(MRR) by using continuous traveling of both wire electrode (i.e. brass wire and zinc-coated brass wire). The present work also analyses the effect of types of wires, such as brass wire and zinc-coated brass wire used during machining of Titanium alloy (Ti-6Al-4V) on Surface roughness (SR) and material removal rate (MRR). This work studies the correlation between various response parameter such SR and MRR by using same machining parameter by for both wires.
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