The lncRNA UCA1 Enhances Pancreatic Cancer EMT by Regulating miR-708-5p and miR-135b-5p: A Bioinformatics Approach.

Background: Pancreatic cancer (PC) is an exceedingly malignant ailment that is not only characterized by its insidious onset and rapid progression but also by its poor therapeutic effects. Recently, emerging evidence has shed light on the significant role that non-coding RNAs (ncRNAs), particularly long ncRNAs (lncRNAs) and microRNAs (miRNAs), play in the pathogenesis of PC. This investigation aimed to construct a network of interactions between miRNAs, lncRNAs, and mRNAs, as well as to perform correlation analyses in the context of PC. Methods: This study carried out in Kerman City, southeastern Iran in 2023. We utilized the GSE119794 dataset from the Gene Expression Omnibus (GEO) to analyze differentially expressed lncRNAs (DE-lncRNAs), miRNAs (DE-miRNAs), and mRNAs (DE-mRNAs). Following the identification of the DE-lncRNAs, DE-mRNAs, and DE-miRNAs, we proceeded to examine differentially expressed epithelialmesenchymal transition (EMT) genes. Subsequently, we utilized the RNAInter database to predict interactions among lncRNAs, miRNAs, and mRNAs. Finally, we employed Cytoscape to visualize and analyze the constructed network. Results: 14 DE-lncRNAs, 14 DE-miRNAs, 545 DE-mRNAs, and 65 DE-EMT from pancreatic cancer and its adjacent tissue RNA-Seq data were identified. 1184 EMT genes from dbEMT were obtained, among which 65 DE-EMT were assigned as EMT genes and correlated with tumor progression. One functional lncRNA (UCA1) was identified as a key functional lncRNA. The area under the ROC curve (AUC) of UCA1 and miR-708-5p were 0.79 and 0.86, respectively. Thus, it is reasonable to believe that this prognostic risk model helps predict PC metastasis. Conclusion: UCA1 is a new lncRNA linked with EMT in PC and contributes to a better knowledge of the regulatory mechanisms related to lncRNAs in PC.

Antisense Oligonucleotide Embedded Context Responsive Nanoparticles Derived from Synthetic Ionizable Lipids for lncRNA Targeted Therapy of Breast Cancer.

The long noncoding RNAs (lncRNA) are primarily associated with several essential gene regulations but are also connected to cancer metabolism and progression. HOTAIR and MALAT1 are two such lncRNAs that are detected in malignancies of various origins and are responsible for the poor prognosis of cancer patients. Due to these factors, the lncRNAs have emerged as prime targets for the development of anticancer therapeutics. However, nonviral delivery of lncRNA-targeted antisense oligonucleotides (ASOs) still remains a critical challenge while maintaining their structural and functional integrity. Herein, we have designed and synthesized a new series of ionizable lipids with variations in their head groups to prepare lipid nanoparticle (LNP) formulation along with cholesterol-based twin cationic lipid and amphiphilic zwitterionic lipid. The context responsiveness of these formulations in delivering the ASOs has been thoroughly investigated by various bioanalytical techniques, and an optimum formulation has been identified. The LNPs are utilized to deliver the ASOs targeting HOTAIR lncRNA in human cancer cell lines and MALAT1 lncRNA in mouse models. This study thus standardizes an advanced nanomaterial system for nonviral gene delivery that has been validated by a considerable reduction in the target lncRNA level under in vitro and a significant reduction in tumor volume under in vivo settings.

Involvement of long non-coding RNA LOXL1-AS1 in the tumourigenesis and development of malignant tumours: a narrative review.

Background and Objective: Long noncoding RNAs (lncRNAs) are involved in a wide variety of physiological and pathological processes in organisms. LncRNAs play a significant role as oncogenic or tumour-suppressing factors in various biological processes associated with malignant tumours and are closely linked to the occurrence and development of malignancies. Lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1) is a recently discovered lncRNA. It is upregulated in various malignant tumours and is associated with pathological characteristics such as tumour size, tumour node metastasis (TNM) staging, lymph node metastasis, and tumour prognosis. LOXL1-AS1 exerts its oncogenic role by competitively binding with multiple microRNAs (miRs), thereby regulating the expression of downstream target genes and controlling relevant signalling pathways. This article aims to explore the structure and the function of LOXL1-AS1, and the relationship between LOXL1-AS1 and the occurrence and development of human malignant tumours to provide a reference for further clinical research. Methods: English literature on LOXL1-AS1 in the occurrence and development of various malignant tumours was searched in PubMed. The main search terms were "LOXL1-AS1", "tumour". Key Content and Findings: This article mainly summarizes the biological processes in which LOXL1-AS1 is involved in various human malignant tumours and the ways in which this lncRNA affects malignant biological behaviours such as proliferation, metastasis, invasion, and apoptosis of tumour cells through different molecular regulatory mechanisms. This article also explores the potential clinical significance and application prospects of LOXL1-AS1, aiming to provide a theoretical basis and reference for the clinical diagnosis, treatment, and screening of prognostic markers for malignant tumours. Conclusions: LOXL1-AS1 acts as a competing endogenous RNA (ceRNA), binding to miRs to regulate downstream target genes and exert its oncogenic effects. LOXL1-AS1 may become a novel molecular biomarker for cancer diagnosis and treatment in humans, and it may also serve as an independent prognostic indicator.

m6A modification of lncRNA PHKA1-AS1 enhances Actinin Alpha 4 stability and promotes non-small cell lung cancer metastasis.

Cancer is a disease with molecular heterogeneity that is closely related to gene mutations and epigenetic changes. The principal histological subtype of lung cancer is non-small cell lung cancer (NSCLC). Long noncoding RNA (lncRNA) is a kind of RNA that is without protein coding function, playing a critical role in the progression of cancer. In this research, the regulatory mechanisms of lncRNA phosphorylase kinase regulatory subunit alpha 1 antisense RNA 1 (PHKA1-AS1) in the progression of NSCLC were explored. The increased level of N6-methyladenosine (m6A) modification in NSCLC caused the high expression of PHKA1-AS1. Subsequently, high-expressed PHKA1-AS1 significantly facilitated the proliferation and metastasis of NSCLC cells, and these effects could be reversed upon the inhibition of PHKA1-AS1 expression, both in vivo and in vitro. Additionally, the target protein of PHKA1-AS1 was actinin alpha 4 (ACTN4), which is known as an oncogene. Herein, PHKA1-AS1 could enhance the protein stability of ACTN4 by inhibiting its ubiquitination degradation process, thus exerting the function of ACTN4 in promoting the progress of NSCLC. In conclusion, this research provided a theoretical basis for further exploring the potential mechanism of NSCLC metastasis and searching novel biomarkers related to the pathogenesis and progression of NSCLC.

Identification of a lactate metabolism-related lncRNAs signature for predicting the prognosis in patients with kidney renal clear cell carcinoma.

Background: Lactate metabolism-related (LMR) long noncoding RNAs (lncRNAs) play significant roles in various cancers, but their impact on kidney renal clear cell carcinoma (KIRC) remains unclear. This study aimed to explore the value of LMR lncRNA and develop a risk model for KIRC. Methods: Data on KIRC patients were downloaded from The Cancer Genome Atlas (TCGA) database. LMR lncRNAs were identified by co-expression, univariate and multivariate analyses, and least absolute shrinkage selection operator (LASSO) regression analysis. Subsequently, a prognostic signature was constructed and its accuracy was verified. To predict the prognosis of KIRC effectively, we established a nomogram based on this information. Enrichment analysis, tumor mutational burden (TMB) analysis, immune status and the therapeutic sensitivities of KIRC patients were also investigated. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of lncRNAs. Results: We constructed and verified a predictive signature based on six LMR lncRNA (LINC00944, AC090772.3, Z83745.1, AP001267.3, AC092296.1, and AL162377.1) to assess the patient prognoses of KIRC. Survival analyses showed a more unfavorable outcome in high-risk patients (P<0.001). Enrichment analysis demonstrated that immune-related pathways were enriched in the high-risk group. Besides, patients classified by risk scores had distinguishable immune status, TMB, response to immunotherapy, and sensitivity to chemotherapy and targeted drugs. Conclusions: The LMR lncRNAs signature has significant implications for prognostic assessment and clinical treatment guidance in KIRC.

The role of long noncoding RNAs in ocular angiogenesis and vascular oculopathy.

BACKGROUND: Long noncoding RNAs (lncRNAs) are RNA transcripts over 200 nucleotides in length that do not code for proteins. Initially considered a genomic mystery, an increasing number of lncRNAs have been shown to have vital roles in physiological and pathological conditions by regulating gene expression through diverse mechanisms depending on their subcellular localization. Dysregulated angiogenesis is responsible for various vascular oculopathies, including diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, and corneal neovascularization. While anti-VEGF treatment is available, it is not curative, and long-term outcomes are suboptimal, and some patients are unresponsive. To better understand these diseases, researchers have investigated the role of lncRNAs in regulating angiogenesis and models of vascular oculopathies. This review summarizes recent research on lncRNAs in ocular angiogenesis, including the pro-angiogenic lncRNAs ANRIL, HOTAIR, HOTTIP, H19, IPW, MALAT1, MIAT, NEAT1, and TUG1, the anti-angiogenic lncRNAs MEG3 and PKNY, and the human/primate specific lncRNAs lncEGFL7OS, discussing their functions and mechanisms of action in vascular oculopathies.

Uncovering the ceRNA Network Related to the Prognosis of Stomach Adenocarcinoma Among 898 Patient Samples.

Stomach adenocarcinoma (STAD) patients are often associated with significantly high mortality rates and poor prognoses worldwide. Among STAD patients, competing endogenous RNAs (ceRNAs) play key roles in regulating one another at the post-transcriptional stage by competing for shared miRNAs. In this study, we aimed to elucidate the roles of lncRNAs in the ceRNA network of STAD, uncovering the molecular biomarkers for target therapy and prognosis. Specifically, a multitude of differentially expressed lncRNAs, miRNAs, and mRNAs (i.e., 898 samples in total) was collected and processed from TCGA. Cytoplasmic lncRNAs were kept for evaluating overall survival (OS) time and constructing the ceRNA network. Differentially expressed mRNAs in the ceRNA network were also investigated for functional and pathological insights. Interestingly, we identified one ceRNA network including 13 lncRNAs, 25 miRNAs, and 9 mRNAs. Among them, 13 RNAs were found related to the patient survival time; their individual risk score can be adopted for prognosis inference. Finally, we constructed a comprehensive ceRNA regulatory network for STAD and developed our own risk-scoring system that can predict the OS time of STAD patients by taking into account the above.

Decoding the regulatory landscape of lncRNAs as potential diagnostic and prognostic biomarkers for gastric and colorectal cancers.

Colorectal cancer (CRC) and gastric cancer (GC) are major contributors to cancer-related mortality worldwide. Despite advancements in understanding molecular mechanisms and improved drug treatments, the overall survival rate for patients remains unsatisfactory. Metastasis and drug resistance are major challenges contributing to the high mortality rate in both CRC and GC. Recent research has shed light on the role of long noncoding RNAs (lncRNAs) in the development and progression of these cancers. LncRNAs regulate gene expression through various mechanisms, including epigenetic modifications and interactions with microRNAs (miRNAs) and proteins. They can serve as miRNA precursors or pseudogenes, modulating gene expression at transcriptional and post-transcriptional levels. Additionally, circulating lncRNAs have emerged as non-invasive biomarkers for the diagnosis, prognosis, and prediction of drug therapy response in CRC and GC. This review explores the intricate relationship between lncRNAs and CRC/GC, encompassing their roles in cancer development, progression, and chemoresistance. Furthermore, it discusses the potential of lncRNAs as therapeutic targets in these malignancies. The interplay between lncRNAs, miRNAs, and tumor microenvironment is also highlighted, emphasizing their impact on the complexity of cancer biology. Understanding the regulatory landscape and molecular mechanisms governed by lncRNAs in CRC and GC is crucial for the development of effective diagnostic and prognostic biomarkers, as well as novel therapeutic strategies. This review provides a comprehensive overview of the current knowledge and paves the way for further exploration of lncRNAs as key players in the management of CRC and GC.

The gut-Snhg9 interplay as a new path to metabolic health.

Parsing the intricate interplay between gut microbiota, gene modulation, and host metabolism remains challenging. Wang et al. employed diverse methods to uncover how the gut microbiota reshapes intestinal lipid metabolism through the lncRNA Snhg9, underscoring the value of systems biology approaches in dissecting host-microbiome relationships involved in metabolic disorders.

Long noncoding RNAs emerge from transposon-derived antisense sequences and may contribute to infection stage-specific transposon regulation in a fungal phytopathogen.

BACKGROUND: The genome of the obligate biotrophic phytopathogenic barley powdery mildew fungus Blumeria hordei is inflated due to highly abundant and possibly active transposable elements (TEs). In the absence of the otherwise common repeat-induced point mutation transposon defense mechanism, noncoding RNAs could be key for regulating the activity of TEs and coding genes during the pathogenic life cycle. RESULTS: We performed time-course whole-transcriptome shotgun sequencing (RNA-seq) of total RNA derived from infected barley leaf epidermis at various stages of fungal pathogenesis and observed significant transcript accumulation and time point-dependent regulation of TEs in B. hordei. Using a manually curated consensus database of 344 TEs, we discovered phased small RNAs mapping to 104 consensus transposons, suggesting that RNA interference contributes significantly to their regulation. Further, we identified 5,127 long noncoding RNAs (lncRNAs) genome-wide in B. hordei, of which 823 originated from the antisense strand of a TE. Co-expression network analysis of lncRNAs, TEs, and coding genes throughout the asexual life cycle of B. hordei points at extensive positive and negative co-regulation of lncRNAs, subsets of TEs and coding genes. CONCLUSIONS: Our work suggests that similar to mammals and plants, fungal lncRNAs support the dynamic modulation of transcript levels, including TEs, during pivotal stages of host infection. The lncRNAs may support transcriptional diversity and plasticity amid loss of coding genes in powdery mildew fungi and may give rise to novel regulatory elements and virulence peptides, thus representing key drivers of rapid evolutionary adaptation to promote pathogenicity and overcome host defense.

Gambogenic Acid Inhibits Invasion and Metastasis of Melanoma through Regulation of lncRNA MEG3.

Cutaneous melanoma is an aggressive cancer, which is the most common type of melanoma. In our previous studies, gambogenic acid (GNA) inhibited the proliferation and migration of melanoma cells. Maternally expressed gene 3 (MEG3) is a long noncoding RNA (lncRNA) that has been shown to have inhibitory effects in a variety of cancers. However, the mechanisms in melanoma progression need to be further investigated. In the current study, we investigated the inhibitory effect of GNA on melanoma and its molecular mechanism through a series of cell and animal experiments. We found that GNA could improve epithelial mesenchymal transition by up-regulating the expression of the lncRNA MEG3 gene, thereby inhibiting melanoma metastasis in vitro and in vivo.

CSNK1G2-AS1 promotes metastasis, colony formation and serves as a biomarker in testicular germ cell tumor cells.

Background/Aim: Some long non-coding RNAs (lncRNAs) have been found to significantly participate in the progression of TGCTs. In comparison to the normal testis, the TGCT tissues showed significantly decreased CSNK1G2-AS1 expression, however, its effect on TGCTs and its mechanism are still unclear. The aim of this study is to investigate the effect of CSNK1G2-AS1 on TGCTs and explore the mechanism underlying its effect on TGCTs. Materials and Methods: In this study, to evaluate the expression of CSNK1G2-AS1 in tissue samples from TGCTs, the UCSC and GEPIA databases were applied and qRT-PCR was conducted. The Kaplan-Meier Plotter was applied to analyze the correlation between CSNK1G2-AS1 methylation levels and the prognosis of TGCTs patients. The assays of MTS, clone formation, transwell, and flow cytometry were performed to investigate the effect of CSNK1G2-AS1 overexpression on the proliferation, metastasis, and apoptosis of TGCT cells, respectively. Finally, western blotting was conducted to determine the expressions of the proteins associated with EMT and AKT. Results: Our study first found that, compared to the normal testis, TGCTs tissue showed significantly decreased CSNK1G2-AS1 expression, and hypomethylation of CSNK1G2-AS1 was significantly correlated with a better prognosis with TGCTs patients. In vitro, we found that overexpression of CSNK1G2-AS1 dramatically promoted the clone formation, invasion, and migration of TGCT cells, but inhibited apoptosis. And CSNK1G2-AS1 overexpression significantly decreased the expression of EMT-associated proteins ZO-1 but increased the expression and phosphorylation of AKT. Conclusions: CSNK1G2-AS1 may play an essential role in the pathogenesis and metastasis of TGCTs through the EMT- and AKT-mediated signal pathways.

Unveiling the Genetic Complexity of Teratozoospermia: Integrated Genomic Analysis Reveals Novel Insights into lncRNAs' Role in Male Infertility.

Male infertility is a global health issue, affecting over 20 million men worldwide. Genetic factors are crucial in various male infertility forms, including teratozoospermia. Nonetheless, the genetic causes of male infertility remain largely unexplored. In this study, we employed whole-genome sequencing and RNA expression analysis to detect differentially expressed (DE) long-noncoding RNAs (lncRNAs) in teratozoospermia, along with mutations that are exclusive to teratozoospermic individuals within these DE lncRNAs regions. Bioinformatic tools were used to assess variants' impact on lncRNA structure, function, and lncRNA-miRNA interactions. Our analysis identified 1166 unique mutations in teratozoospermic men within DE lncRNAs, distinguishing them from normozoospermic men. Among these, 64 variants in 23 lncRNAs showed potential regulatory roles, 7 variants affected 4 lncRNA structures, while 37 variants in 17 lncRNAs caused miRNA target loss or gain. Pathway Enrichment and Gene Ontology analyses of the genes targeted by the affected miRNAs revealed dysregulated pathways in teratozoospermia and a link between male infertility and cancer. This study lists novel variants and lncRNAs associated for the first time with teratozoospermia. These findings pave the way for future studies aiming to enhance diagnosis and therapy in the field of male infertility.

REST-repressed lncRNA LINC01801 induces neuroendocrine differentiation in prostate cancer via transcriptional activation of autophagy.

The association between REST reduction and the development of neuroendocrine prostate cancer (NEPC), a novel drug-resistant and lethal variant of castration-resistant prostate cancer (CRPC), is well established. To better understand the mechanisms underlying this process, we aimed to identify REST-repressed long noncoding RNAs (lncRNAs) that promote neuroendocrine differentiation (NED), thus facilitating targeted therapy-induced resistance. In this study, we used data from REST knockdown RNA sequencing combined with siRNA screening to determine that LINC01801 was upregulated and played a crucial role in NED in prostate cancer (PCa). Using The Cancer Genome Atlas (TCGA) prostate adenocarcinoma database and CRPC samples collected in our laboratory, we demonstrated that LINC01801 expression is upregulated in NEPC. Functional experiments revealed that overexpression of LINC01801 had a slight stimulatory effect on the NED of LNCaP cells, while downregulation of LINC01801 significantly inhibited the induction of NED. Mechanistically, LINC01801 is transcriptionally repressed by REST, and transcriptomic analysis revealed that LINC01801 preferentially affects the autophagy pathway. LINC01801 was found to function as a competing endogenous RNA (ceRNA) to regulate the expression of autophagy-related genes by sponging hsa-miR-6889-3p in prostate cancer cells. In conclusion, our data expand the current knowledge of REST-induced NED and highlight the contribution of the REST-LINC01801-hsa-miR-6889-3p axis to autophagic induction, which may provide promising avenues for therapeutic opportunities.

Construction and Validation of a Reliable Disulfidptosis-Related LncRNAs Signature of the Subtype, Prognostic, and Immune Landscape in Colon Cancer.

Disulfidptosis, a novel form of regulated cell death (RCD) associated with metabolism, represents a promising intervention target in cancer therapy. While abnormal lncRNA expression is associated with colon cancer development, the prognostic potential and biological characteristics of disulfidptosis-related lncRNAs (DRLs) remain unclear. Consequently, the research aimed to discover a novel indication of DRLs with significant prognostic implications, and to investigate their possible molecular role in the advancement of colon cancer. Here, we acquired RNA-seq data, pertinent clinical data, and genomic mutations of colon adenocarcinoma (COAD) from the TCGA database, and then DRLs were determined through Pearson correlation analysis. A total of 434 COAD patients were divided in to three subgroups through clustering analysis based on DRLs. By utilizing univariate Cox regression, the least absolute shrinkage and selection operator (LASSO) algorithm, and multivariate Cox regression analysis, we ultimately created a prognostic model consisting of four DRLs (AC007728.3, AP003555.1, ATP2B1.AS1, and NSMCE1.DT), and an external database was used to validate the prognostic features of the risk model. According to the Kaplan-Meier curve analysis, patients in the low-risk group exhibited a considerably superior survival time in comparison to those in the high-risk group. Enrichment analysis revealed a significant association between metabolic processes and the genes that were differentially expressed in the high- and low-risk groups. Additionally, significant differences in the tumor immune microenvironment landscape were observed, specifically pertaining to immune cells, function, and checkpoints. High-risk patients exhibited a low likelihood of immune evasion, as indicated by the Tumor Immune Dysfunction and Exclusion (TIDE) analysis. Patients who exhibit both a high risk and high Tumor Mutational Burden (TMB) experience the least amount of time for survival, whereas those belonging to the low-risk and low-TMB category demonstrate the most favorable prognosis. In addition, the risk groups determined by the 4-DRLs signature displayed distinct drug sensitivities. Finally, we confirmed the levels of expression for four DRLs through rt-qPCR in both tissue samples from colon cancer patients and cell lines. Taken together, the first 4-DRLs-based signature we proposed may serve for a hopeful instrument for forecasting the prognosis, immune landscape, and therapeutic responses in colon cancer patients, thereby facilitating optimal clinical decision-making.

RNA circuits and RNA-binding proteins in T cells.

RNA is integral to the regulatory circuits that control cell identity and behavior. Cis-regulatory elements in mRNAs interact with RNA-binding proteins (RBPs) that can alter RNA sequence, stability, and translation into protein. Similarly, long noncoding RNAs (lncRNAs) scaffold ribonucleoprotein complexes that mediate transcriptional and post-transcriptional regulation of gene expression. Indeed, cell programming is fundamental to multicellular life and, in this era of cellular therapies, it is of particular interest in T cells. Here, we review key concepts and recent advances in our understanding of the RNA circuits and RBPs that govern mammalian T cell differentiation and immune function.

A risk model constructed using 14 N6-methyladenosine-related lncRNAs as a new prognostic marker that correlates with the immunomodulatory effect and drug sensitivity in colorectal cancer.

Background: Colorectal cancer (CRC) remains the most common gastrointestinal malignancy. Despite multimodal therapy, its mortality is high due to recurrence and metastasis. This study developed and verified a risk model consisting of 14 N6-methyladenosine (m6A) long noncoding RNAs (lncRNAs) to assess the prognosis of patients with CRC and investigated its relevance to immune regulation and drug sensitivity. Methods: The gene expression profiles and clinical data of 446 patients with CRC were retrieved from The Cancer Genome Atlas (TCGA). 14 lncRNAs were screened using the Gene Co-expression Network (corFilter =0.5, P<0.001), and univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct the optimal risk model. The predictive performance and clinical applicability of the model were next verified. In addition, we performed Gene Ontology (GO) enrichment analysis to identify potential biological functions and detected the difference in tumor mutational burden (TMB), immune function, and sensitivity to immunotherapy and other drugs between the high- and low-risk groups to evaluate the application of the constructed risk model in depth. Results: The model was found to be an appropriate marker for predicting the prognosis of patients with CRC, independent of other clinical features, and demonstrated good precision and broad clinical applicability. It correlated with pathways in the development of cancer and immune-related functions, and patients in the high-risk group had higher tumor immune dysfunction and escape (TIDE) scores. Furthermore, we found significant differences in the overall survival (OS) between patients in the high- and low-tumor mutation burden (TMB) groups, which may work in conjunction with the constructed model to better predict patients' prognosis. Finally, we identified 12 drugs, including A-443654 and sorafenib, with lower half maximal inhibitory concentration (IC50) values in the high-risk group. Conversely, 21 drugs, including gemcitabine and rapamycin, had lower IC50 values in the low-risk group. Conclusions: We constructed a risk model based on 14 m6A-related lncRNAs that could predict the prognosis of patients with CRC and provided additional therapeutic ideas for their treatment. These findings may additionally serve as a foundation for further studies on regulating CRC via m6A-related lncRNAs.

Identification and validation of an epithelial-mesenchymal transition-related lncRNA pairs prognostic model for gastric cancer.

Background: Gastric cancer (GC) is a common malignancy. A mounting body of evidence has demonstrated the correlation between GC prognosis and epithelial-mesenchymal transition (EMT)-related biomarkers. This research constructed an available model using EMT-related long noncoding RNA (lncRNA) pairs to predict the survival for GC patients. Methods: The transcriptome data along with clinical information on GC samples were derived from The Cancer Genome Atlas (TCGA). Differentially expressed EMT-related lncRNAs were acquired and paired. Univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were applied to filter lncRNA pairs, and the risk model was built to investigate its effect on the prognosis of GC patients. Then, the areas under the receiver operating characteristic curves (AUCs) were calculated and the cutoff point for distinguishing low- or high-risk GC patients was identified. And the predictive ability of this model was tested in the GSE62254. Furthermore, the model was evaluated from the perspectives of survival time, clinicopathological parameters, infiltration of immunocytes, and functional enrichment analysis. Results: The risk model was built by using the identified twenty EMT-related lncRNA pairs, and it was not necessary to know the specific expression level of each lncRNA. Survival analysis pointed out that GC patients with high risk had poorer outcomes. Additionally, this model could be an independent prognostic variable for GC patients. The accuracy of the model was also verified in the testing set. Conclusions: The new predictive model constructed here is composed of EMT-related lncRNA pairs, with reliable prognostic values, and can be utilized to predict the survival of GC.

Transcriptome-wide 5-methylcytosine modification profiling of long non-coding RNAs in A549 cells infected with H1N1 influenza A virus.

BACKGROUND: In recent years, accumulating evidences have revealed that influenza A virus (IAV) infections induce significant differential expression of host long noncoding RNAs (lncRNAs), some of which play important roles in the regulation of virus-host interactions and determining the virus pathogenesis. However, whether these lncRNAs bear post-translational modifications and how their differential expression is regulated remain largely unknown. In this study, the transcriptome-wide 5-methylcytosine (m5C) modification of lncRNAs in A549 cells infected with an H1N1 influenza A virus was analyzed and compared with uninfected cells by Methylated RNA immunoprecipitation sequencing (MeRIP-Seq). RESULTS: Our data identified 1317 upregulated m5C peaks and 1667 downregulated peaks in the H1N1 infected group. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the differentially modified lncRNAs were associated with protein modification, organelle localization, nuclear export and other biological processes. Furthermore, conjoint analysis of the differentially modified (DM) and differentially expressed (DE) lncRNAs identified 143 'hyper-up', 81 'hypo-up', 6 'hypo-down' and 4 'hyper-down' lncRNAs. GO and KEGG analyses revealed that these DM and DE lncRNAs were predominantly associated with pathogen recognition and disease pathogenesis pathways, indicating that m5C modifications could play an important role in the regulation of host response to IAV replication by modulating the expression and/or stability of lncRNAs. CONCLUSION: This study presented the first m5C modification profile of lncRNAs in A549 cells infected with IAV and demonstrated a significant alteration of m5C modifications on host lncRNAs upon IAV infection. These data could give a reference to future researches on the roles of m5C methylation in virus infection.

Association of Long Noncoding RNA Expression Signatures with Stress-Induced Myocardial Perfusion Defects.

Stress-induced myocardial perfusion defects found in dipyridamole-thallium-201 single-photon emission computed tomography imaging may indicate vascular perfusion abnormalities and risk of obstructive or nonobstructive coronary heart disease. Besides nuclear imaging and subsequent coronary angiography (CAG), no blood test can indicate whether dysregulated homeostasis is associated with stress-induced myocardial perfusion defects. This study investigated the expression signature of long noncoding RNAs (lncRNAs) and genes involved in vascular inflammation and stress response in the blood of patients with stress-induced myocardial perfusion abnormalities (n = 27). The results revealed an expression signature consisting of the upregulation of RMRP (p < 0.01) and downregulations of THRIL (p < 0.01) and HIF1A (p < 0.01) among patients with a positive thallium stress test and no significant coronary artery stenosis within 6 months after baseline treatment. We developed a scoring system based on the expression signatures of RMRP, MIAT, NTT, MALAT1, HSPA1A, and NLRP3 to predict the need for further CAG among patients with moderate-to-significant stress-induced myocardial perfusion defects (area under the receiver operating characteristic curve = 0.963). Therefore, we identified a dysregulated expression profile of lncRNA-based genes in the blood that could be valuable for the early detection of vascular homeostasis imbalance and personalized therapy.