Function Of Non-coding RNAs Research Articles

The diagnostic role and mechanistic functions of exosomal lncRNAs in prostate cancer.

Exosomes are small membrane-enclosed vesicles that are released by most living cells and harbor a diverse array of proteins, nucleic acids, and lipid cargos. These exosomes offer valuable biomarkers that may offer insights regarding as a range of physiological and pathological processes, including immune responses, cancer development, pregnancy, and diseases of the central nervous system. With the development of high-throughput technologies, the vital functions of long non-coding RNAs (lncRNAs) have been gradually entered people's vision and become new research hotspots. Nowadays, lncRNAs can play important roles in cancer progression by combining with miRNAs, activating molecular targets and other ways, and are also related to the diagnosis, treatment and prognosis for cancer, such as prostate cancer. Current review focused on the summary of diagnostic roles and mechanistic functions about exosomal lncRNAs in prostate cancer.

Structure-based screening for functional non-coding RNAs in fission yeast identifies a factor repressing untimely initiation of sexual differentiation.

Non-coding RNAs (ncRNAs) ubiquitously exist in normal and cancer cells. Despite their prevalent distribution, the functions of most long ncRNAs remain uncharacterized. The fission yeast Schizosaccharomyces pombe expresses >1800 ncRNAs annotated to date, but most unconventional ncRNAs (excluding tRNA, rRNA, snRNA and snoRNA) remain uncharacterized. To discover the functional ncRNAs, here we performed a combinatory screening of computational and biological tests. First, all S. pombe ncRNAs were screened in silico for those showing conservation in sequence as well as in secondary structure with ncRNAs in closely related species. Almost a half of the 151 selected conserved ncRNA genes were uncharacterized. Twelve ncRNA genes that did not overlap with protein-coding sequences were next chosen for biological screening that examines defects in growth or sexual differentiation, as well as sensitivities to drugs and stresses. Finally, we highlighted an ncRNA transcribed from SPNCRNA.1669, which inhibited untimely initiation of sexual differentiation. A domain that was predicted as conserved secondary structure by the computational operations was essential for the ncRNA to function. Thus, this study demonstrates that in silico selection focusing on conservation of the secondary structure over species is a powerful method to pinpoint novel functional ncRNAs.

Gene Networks Involved in Plant Heat Stress Response and Tolerance.

Global warming is an environmental problem that cannot be ignored. High temperatures seriously affect the normal growth and development of plants, and threaten the development of agriculture and the distribution and survival of species at risk. Plants have evolved complex but efficient mechanisms for sensing and responding to high temperatures, which involve the activation of numerous functional proteins, regulatory proteins, and non-coding RNAs. These mechanisms consist of large regulatory networks that regulate protein and RNA structure and stability, induce Ca2+ and hormone signal transduction, mediate sucrose and water transport, activate antioxidant defense, and maintain other normal metabolic pathways. This article reviews recent research results on the molecular mechanisms of plant response to high temperatures, highlighting future directions or strategies for promoting plant heat tolerance, thereby helping to identify the regulatory mechanisms of heat stress responses in plants.

Biogenesis of telomerase RNA from a protein-coding mRNA precursor

Telomerase is a eukaryotic ribonucleoprotein (RNP) enzyme that adds DNA repeats onto chromosome ends to maintain genomic stability and confer cellular immortality in cancer and stem cells. The telomerase RNA (TER) component is essential for telomerase catalytic activity and provides the template for telomeric DNA synthesis. The biogenesis of TERs is extremely divergent across eukaryotic kingdoms, employing distinct types of transcription machinery and processing pathways. In ciliates and plants, TERs are transcribed by RNA polymerase III (Pol III), while animal and ascomycete fungal TERs are transcribed by RNA Pol II and share biogenesis pathways with small nucleolar RNA (snoRNA) and small nuclear RNA (snRNA), respectively. Here, we report an unprecedented messenger RNA (mRNA)-derived biogenesis pathway for the 1,291 nucleotide TER from the basidiomycete fungus Ustilago maydis. The U. maydis TER (UmTER) contains a 5'-monophosphate, distinct from the 5' 2,2,7-trimethylguanosine (TMG) cap common to animal and ascomycete fungal TERs. The mature UmTER is processed from the 3'-untranslated region (3'-UTR) of a larger RNA precursor that possesses characteristics of mRNA including a 5' 7-methyl-guanosine (m7G) cap, alternative splicing of introns, and a poly(A) tail. Moreover, this mRNA transcript encodes a protein called Early meiotic induction protein 1 (Emi1) that is conserved across dikaryotic fungi. A recombinant UmTER precursor expressed from an mRNA promoter is processed correctly to yield mature UmTER, confirming an mRNA-processing pathway for producing TER. Our findings expand the plethora of TER biogenesis mechanisms and demonstrate a pathway for producing a functional long noncoding RNA from a protein-coding mRNA precursor.

Whole-transcriptome sequencing and ceRNA interaction network of temporomandibular joint osteoarthritis.

Purpose: The aim of this study was to conduct a comprehensive transcriptomic analysis to explore the potential biological functions of noncoding RNA (ncRNAs) in temporomandibular joint osteoarthritis (TMJOA). Methods: Whole transcriptome sequencing was performed to identify differentially expressed genes (DEGs) profiles between the TMJOA and normal groups. The functions and pathways of the DEGs were analyzed using Metascape, and a competitive endogenous RNA (ceRNA) network was constructed using Cytoscape software. Results: A total of 137 DEmRNAs, 65 DEmiRNAs, 132 DElncRNAs, and 29 DEcircRNAs were identified between the TMJOA and normal groups. Functional annotation of the DEmRNAs revealed that immune response and apoptosis are closely related to TMJOA and also suggested key signaling pathways related to TMJOA, including chronic depression and PPAR signaling pathways. We identified vital mRNAs, including Klrk1, Adipoq, Cryab, and Hspa1b. Notably, Adipoq expression in cartilage was significantly upregulated in TMJOA compared with normal groups (10-fold, p < 0.001). According to the functional analysis of DEmRNAs regulated by the ceRNA network, we found that ncRNAs are involved in the regulation of autophagy and apoptosis. In addition, significantly DEncRNAs (lncRNA-COX7A1, lncRNA-CHTOP, lncRNA-UFM1, ciRNA166 and circRNA1531) were verified, and among these, circRNA1531 (14.5-fold, p < 0.001) and lncRNA-CHTOP (14.8-fold, p < 0.001) were the most significantly downregulated ncRNAs. Conclusion: This study showed the potential of lncRNAs, circRNAs, miRNAs, and mRNAs may as clinical biomarkers and provides transcriptomic insights into their functional roles in TMJOA. This study identified the transcriptomic signatures of mRNAs associated with immunity and apoptosis and the signatures of ncRNAs associated with autophagy and apoptosis and provides insight into ncRNAs in TMJOA.

LncRNA UCA1 induces autophagic gene expression via epigenetic regulation mediated by ATG16L1 and miR-132-3p in SH-SY5Y cells treated with retinoic acid

Epilepsy is a chronic brain disease with recurrent seizures. Autophagy plays a crucial role in the progression of epilepsy. This study aimed to explore the function and intrinsic mechanism of the long non-coding RNA (lncRNA) UCA1/miR-132-3p/ATG16L1 axis in epilepsy via regulation of autophagy. The expression of lncRNA UCA1, miR-132-3p and ATG16L1 was measured in serum from epileptic patients by quantitative RT-PCR. A SH-SY5Y cell model was further constructed using retinoic acid to investigate the UCA1/ miR-132-3p/ATG16L1 axis by quantitative RT-PCR, western blotting, fluorescence in situ hybridisation, RNA immunoprecipitation, chromatin immunoprecipitation, and a dual-luciferase reporter gene assay. In the serum of epileptic patients, the level of lncRNA UCA1 and ATG16L1 was reduced and miR-132-3p elevated, compared to controls. Similarly, in the SH-SY5Y cell model, the level of lncRNA UCA1 and ATG16L1 was reduced and miR-132-3p elevated in retinoic acid-treated cells; lncRNA UCA1 was mainly located in the cytoplasm. lncRNA UCA1 overexpression was shown to promote autophagic gene expression, which was reversed by miR-132-3p overexpression. Moreover, autophagic gene expression induced by miR-132-3p knockdown was reversed by ATG16L1 knockdown. Based on precipitation assays, lncRNA UCA1 and miR-132-3p were shown to form a complex with the transcription factor, EZH2, and miR-132-3p was shown to interact with ATG16L1 based on a luciferase assay. Finally, lncRNA UCA1 was shown to negatively regulate miR-132-3p expression, and miR-132-3p was shown to negatively regulate ATG16L1. In this cell model, lncRNA UCA1 promotes autophagic gene expression via epigenetic regulation mediated by ATG16L1 and miR-132-3p.

Comprehensive analysis of somatic mutator-derived and immune infiltrates related lncRNA signatures of genome instability reveals potential prognostic biomarkers involved in non-small cell lung cancer.

Background: The function and features of long non-coding RNAs (lncRNAs) are already attracting attention and extensive research on their role as biomarkers of prediction in lung cancer. However, the signatures that are both related to genomic instability (GI) and tumor immune microenvironment (TIME) have not yet been fully explored in previous studies of non-small cell lung cancer (NSCLC). Method: The clinical characteristics, RNA expression profiles, and somatic mutation information of patients in this study came from The Cancer Genome Atlas (TCGA) database. Cox proportional hazards regression analysis was performed to construct genomic instability-related lncRNA signature (GIrLncSig). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the potential functions of lncRNAs. CIBERSORT was used to calculate the proportion of immune cells in NSCLC. Result: Eleven genomic instability-related lncRNAs in NSCLC were identified, then we established a prognostic model with the GIrLncSig ground on the 11 lncRNAs. Through the computed GIrLncSig risk score, patients were divided into high-risk and low-risk groups. By plotting ROC curves, we found that patients in the low-risk group in the test set and TCGA set had longer overall survival than those in the high-risk group, thus validating the survival predictive power of GIrLncSig. By stratified analysis, there was still a significant difference in overall survival between high and low risk groups of patients after adjusting for other clinical characteristics, suggesting the prognostic significance of GIrLncSig is independent. In addition, combining GIrLncSig with TP53 could better predict clinical outcomes. Besides, the immune microenvironment differed significantly between the high-risk and the low-risk groups, patients with low risk scores tend to have upregulation of immune checkpoints and chemokines. Finally, we found that high-risk scores were associated with increased sensitivity to chemotherapy. Conclusion: we provided a new perspective on lncRNAs related to GI and TIME and revealed the worth of them in immune infiltration and immunotherapeutic response. Besides, we found that the expression of AC027288.1 is associated with PD-1 expression, which may be a potential prognostic marker in immune checkpoint inhibitor response to improve the prediction of clinical survival in NSCLC patients.

Roles of long noncoding RNAs and small extracellular vesicle-long noncoding RNAs in type 2 diabetes.

The prevalence of a high-energy diet and a sedentary lifestyle has increased the incidence of type 2 diabetes (T2D). T2D is a chronic disease characterized by high blood glucose levels and insulin resistance in peripheral tissues. The pathological mechanism of this disease is not fully clear. Accumulated evidence has shown that noncoding RNAs have an essential regulatory role in the progression of diabetes and its complications. The roles of small noncoding RNAs, such as miRNAs, in T2D, have been extensively investigated, while the function of long noncoding RNAs (lncRNAs) in T2D has been unstudied. It has been reported that lncRNAs in T2D play roles in the regulation of pancreatic function, peripheral glucose homeostasis and vascular inflammation. In addition, lncRNAs carried by small extracellular vesicles (sEV) were shown to mediate communication between organs and participate in diabetes progression. Some sEV lncRNAs derived from stem cells are being developed as potential therapeutic agents for diabetic complications. In this review, we summarize the current knowledge relating to lncRNA biogenesis, the mechanisms of lncRNA sorting into sEV and the regulatory roles of lncRNAs and sEV lncRNAs in diabetes. Knowledge of lncRNAs and sEV lncRNAs in diabetes will aid in the development of new therapeutic drugs for T2D in the future.

LncRNA PSR Regulates Vascular Remodeling Through Encoding a Novel Protein Arteridin.

Vascular smooth muscle cells (VSMCs) phenotype switch from contractile to proliferative phenotype is a pathological hallmark in various cardiovascular diseases. Recently, a subset of long noncoding RNAs was identified to produce functional polypeptides. However, the functional impact and regulatory mechanisms of long noncoding RNAs in VSMCs phenotype switching remain to be fully elucidated. To illustrate the biological function and mechanism of a VSMC-enriched long noncoding RNA and its encoded peptide in VSMC phenotype switching and vascular remodeling. We identified a VSMC-enriched transcript encoded by a previously uncharacterized gene, which we called phenotype switching regulator (PSR), which was markedly upregulated during vascular remodeling. Although PSR was annotated as a long noncoding RNA, we demonstrated that the lncPSR (PSR transcript) also encoded a protein, which we named arteridin. In VSMCs, both arteridin and lncPSR were necessary and sufficient to induce phenotype switching. Mechanistically, arteridin and lncPSR regulate downstream genes by directly interacting with a transcription factor YBX1 (Y-box binding protein 1) and modulating its nuclear translocation and chromatin targeting. Intriguingly, the PSR transcription was also robustly induced by arteridin. More importantly, the loss of PSR gene or arteridin protein significantly attenuated the vascular remodeling induced by carotid arterial injury. In addition, VSMC-specific inhibition of lncPSR using adeno-associated virus attenuated Ang II (angiotensin II)-induced hypertensive vascular remodeling. PSR is a VSMC-enriched gene, and its transcript IncPSR and encoded protein (arteridin) coordinately regulate transcriptional reprogramming through a shared interacting partner, YBX1. This is a previously uncharacterized regulatory circuit in VSMC phenotype switching during vascular remodeling, with lncPSR/arteridin as potential therapeutic targets for the treatment of VSMC phenotype switching-related vascular remodeling.

Evaluation of miR-146a (rs2910164) polymorphism in coronary artery disease: Case-control and silico analysis

As the most common cause of mortality, cardiovascular disease is a serious problem in the health system worldwide. The function of a small non-coding RNA, miR-146a, in inflammation and myocardial hypertrophy has been determined previously. In this experiment, we aim to assess the role of miR-146a polymorphism in cardiovascular disease. In this case-control study, 297 cardiovascular disease (CAD) patients and 306 healthy controls were enrolled. The polymerase chain reaction (PCR) and the restriction fragment length polymorphism (RFLP) were applied to determine the genotype of the miR-146a (rs2910164) SNP. The secondary structure of miR-146a and potential protein interactions of two alternative variants, C and G, were determined with in silico and computational analysis. Statistically, P < 0.05 was considered significant. The frequency of genotypes including CC, CG, and GG related to miR-146a (rs2910164) polymorphism showed no significant difference between CAD patients and controls (P = 0.928). The results of in silico and computational analysis reported that G and C-variants may support different RNA folding arrangements and promote different protein binding sites. However, miR-146a gene polymorphism (rs2910164) has no significant association with CAD in the study population.

Competing Endogenous RNA (ceRNA) Networks and Splicing Switches in Cervical Cancer: HPV Oncogenesis, Clinical Significance and Therapeutic Opportunities.

Cervical cancer (CC) is the primary cause of female cancer fatalities in low-middle-income countries (LMICs). Persistent infections from the human papillomavirus (HPV) can result in cervical cancer. However, numerous different factors influence the development and progression of cervical cancer. Transcriptomic knowledge of the mechanisms with which HPV causes cervical cancer pathogenesis is growing. Nonetheless, there is an existing gap hindering the development of therapeutic approaches and the improvement of patient outcomes. Alternative splicing allows for the production of numerous RNA transcripts and protein isoforms from a single gene, increasing the transcriptome and protein diversity in eukaryotes. Cancer cells exhibit astounding transcriptome modifications by expressing cancer-specific splicing isoforms. High-risk HPV uses cellular alternative splicing events to produce viral and host splice variants and proteins that drive cancer progression or contribute to distinct cancer hallmarks. Understanding how viruses utilize alternative splicing to drive pathogenesis and tumorigenesis is essential. Although research into the role of miRNAs in tumorigenesis is advancing, the function of other non-coding RNAs, including lncRNA and circRNA, has been understudied. Through their interaction with mRNA, non-coding RNAs form a network of competing endogenous RNAs (ceRNAs), which regulate gene expression and promote cervical cancer development and advancement. The dysregulated expression of non-coding RNAs is an understudied and tangled process that promotes cervical cancer development. This review will present the role of aberrant alternative splicing and immunosuppression events in HPV-mediated cervical tumorigenesis, and ceRNA network regulation in cervical cancer pathogenesis will also be discussed. Furthermore, the therapeutic potential of splicing disruptor drugs in cervical cancer will be deliberated.

Proteomics characterization of the adenovirus VA1 non-coding RNA on the landscape of cellular proteome

Abstract Objectives Gene therapy using adenoviruses has shown tremendous promise in animal and human models in the past. The tumor responses achieved by these viruses were either because of their oncolytic properties or therapeutic genes expressed from the genome of the virus. We have previously shown enhanced viral replication in cell models that have lost or lower expression of the cyclin dependent kinases inhibitor (p21/Waf-1). Beside the early onset of many viral genes in the p21/Waf-1 knock out cell model, we observed a significantly higher copy number for the viral VA1 but non VA2 non-coding RNA transcripts. In this study we investigated the effect of adenoviral VA1 non-coding RNA on the landscape of cellular proteins. Methods Using a DU145 cell line as a model that was transiently transfected with a plasmid carrying the adenoviral VA1 non-coding RNA, we were able to study changes in the proteome and the cellular cascade of the cells. Using state of the art global proteomics analyses of the differentially expressed proteins between the VA1 overexpressed and control cells demonstrated how the early onset of VA1 transcript affected cellular machinery. Results Using a 1.5 fold cut off between the down-regulated or overexpressing proteins, we were able to demonstrate how the non-coding VA1 gene might be responsible for suppressing the proteasome degradation, the endocytic and lysosomal pathways. Similarly, overexpression of the non-coding VA1 transcript was responsible for the upregulation (1.5 fold) of approximately 40 different proteins in the spliceosome machinery. Conclusions These data demonstrated how the non-coding VA1 RNA functioned independently of any other viral proteins in modulating the cell signaling cascades to promote viral propagation. To our knowledge this is the first report to investigate the function of VA1 non-coding RNA on the cellular proteome.

LncRNA OIP5-AS1 Mitigates Bupivacaine-Induced Neurotoxicity in Dorsal Root Ganglion Neurons Through Regulating NFAT5 Expression via Sponging miR-34b.

Bupivacaine (BUP), which is widely used in anesthesia, can cause neurotoxicity and neurological abnormalities. This work intended to study the function of long non-coding RNA (lncRNA) OIP5 antisense RNA 1 (OIP5-AS1) in BUP-triggered neurotoxicity. OIP5-AS1, microRNA (miR)-34b, and nuclear factor of activated T cells 5 (NFAT5) levels were examined via real-time quantitative PCR (RT-qPCR). Cell proliferation, caspase-3 activity, and apoptosis were assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), caspase-3 activity, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. The regulatory relationships between miR-34b and OIP5-AS1 or NFAT5 were validated via RNA binding protein immunoprecipitation (RIP) and dual-luciferase reporter assays. Our data demonstrated that OIP5-AS1 and NFAT5 levels were downregulated and miR-34b was upregulated upon exposure to BUP. Functional assays implied that the OIP5-AS1 deficiency impeded cell proliferation and enhanced the apoptosis of DRG neurons, while OIP5-AS1 addition reversed these changes. Moreover, OIP5-AS1 could bind to miR-34b and OIP5-AS1 regulated BUP-induced neurotoxicity via miR-34b. Besides, miR-34b could directly interact with NFAT5. Augmentation of miR-34b impeded cell proliferation and expedited the apoptosis and caspase-3 activity, while NFAT5 addition neutralized these impacts. Finally, it was verified that OIP5-AS1 could upregulate NFAT5 through sponging miR-34b. In sum, our results disclosed that OIP5-AS1 ameliorated BUP-caused neurotoxicity via regulating the miR-34b/NFAT5 axis, suggesting that OIP5-AS1 might be a promising therapeutic target for the treatment of BUP-induced neurotoxicity.

The pattern of DNA methylation alteration, and its association with the expression changes of non-coding RNAs and mRNAs in Moso bamboo under abiotic stress

Epigenetic changes play an important role in plant growth and development and in stress response. However, DNA methylation pattern and its relationship with the expression changes of non-coding RNAs and mRNAs of Moso bamboo in response to abiotic stress is still largely unknown. In this work, we used whole-genome bisulfite sequencing in combination with whole-transcriptome sequencing to analyze the DNA methylation and transcription patterns of mRNAs and non-coding RNAs in Moso bamboo under abiotic stresses such as cold, heat, ultraviolet (UV) and salinity. We found that CHH methylation in the promoter region was positively correlated with gene expression, while CHG and CHH methylations in the gene body regions were negatively associated with gene expression. Moreover, CG and CHG methylations in the promoter regions were negatively correlated with the transcript abundance of long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs). Similarly, the methylation levels of three contexts in the genic regions were negatively correlated with the transcript abundance of lncRNAs and miRNAs but positively correlated with that of circRNAs. In addition, we suggested that the reduction of 21-nt and 24-nt small interfering RNA (siRNA) expression tended to increase methylation levels in the genic regions. We found that stress-responsive genes such as CRPK1, HSFB2A and CIPK were differentially methylated and expressed. Our results also proposed that DNA methylation may regulate the expression of the transcription factors (TFs) and plant hormone signalling genes such as IAA9, MYC2 and ERF110 in response to abiotic stress. This study firstly reports the abiotic stress-responsive DNA methylation pattern and its involvement of expression of coding RNAs and non-coding RNAs in Moso bamboo. The results expand the knowledge of epigenetic mechanisms in Moso bamboo under abiotic stress and support in-depth deciphering of the function of specific non-coding RNAs in future studies.

BAT-Net: An enhanced RNA Secondary Structure prediction via bidirectional GRU-based network with attention mechanism

Background:RNA Secondary Structure (RSS) has drawn growing concern, both for their pivotal roles in RNA tertiary structures prediction and critical effect in penetrating the mechanism of functional non-coding RNA. Computational techniques that can reduce the in vitro and in vivo experimental costs have become popular in RSS prediction. However, as an NP-hard problem, there is room for improvement that the validity of the prediction RSS with pseudoknots in traditional machine learning predictors. Results:In this essay, by integrating the bidirectional GRU (Gated Recurrent Unit) with the attention, we propose a multilayered neural network called BAT-Net to predict RSS. Different from the state-of-the-art works, BAT-Net can not only make full use of the information about the direct predecessor and direct successor of the predicted base in the RNA sequence but also dynamically adjust the corresponding loss function. The experimental results on five representative datasets extracted from the RNA STRAND database show that the sensitivity, precision, accuracy, and MCC (Matthews Correlation Coefficient) of the BAT-Net have improved by 8.52%, 8.28%, 5.66% and 9.82%, respectively, compared with the benchmark approaches on the best averages. Conclusions:BAT-Net can provide users with more credible RSS results since it has further utilized the source information of the dataset. Comparative results show that the proposed BAT-Net is superior to the other existing methods on the relevant indicators.

Predicting prognosis and immune responses in hepatocellular carcinoma based on N7-methylguanosine-related long noncoding RNAs.

Background: Hepatocellular carcinoma (HCC), which has high rates of recurrence and metastasis and is the main reason and the most common tumor for cancer mortality worldwide, has an unfavorable prognosis. N7-methylguanosine (m7G) modification can affect the formation and development of tumors by affecting gene expression and other biological processes. In addition, many previous studies have confirmed the unique function of long noncoding RNAs (lncRNAs) in tumor progression; however, studies exploring the functions of m7G-related lncRNAs in HCC patients has been limited. Methods: Relevant RNA expression information was acquired from The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov), and m7G-related lncRNAs were identified via gene coexpression analysis. Afterward, univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate regression analyses were implemented to construct an ideal risk model whose validity was verified using Kaplan–Meier survival, principal component, receiver operating characteristic (ROC) curve, and nomogram analyses. In addition, the potential functions of lncRNAs in the novel signature were explored through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and gene set enrichment analysis (GSEA). At last, in both risk groups and subtypes classified based on the expression of the risk-related lncRNAs, we analyzed the immune characteristics and drug sensitivity of patients. Results: After rigorous screening processes, we built a model based on 11 m7G-related lncRNAs for predicting patient overall survival (OS). The results suggested that the survival status of patients with high-risk scores was lower than that of patients with low-risk scores, and a high-risk score was related to malignant clinical features. Cox regression analysis showed that the m7G risk score was an independent prognostic parameter. Moreover, immune cell infiltration and immunotherapy sensitivity differed between the risk groups. Conclusion: The m7G risk score model constructed based on 11 m7G-related lncRNAs can effectively assess the OS of HCC patients and may offer support for making individualized treatment and immunotherapy decisions for HCC patients.

LncRNA FGD5-AS1 potentiates autophagy-associated doxorubicin resistance by regulating the miR-154-5p/WNT5A axis in osteosarcoma.

Osteosarcoma is prevalent in children and adolescent. The oncogenic function of long-chain noncoding RNA (lncRNA) FGD5 antisense RNA 1 (FGD5-AS1) has been reported. However, the function of FGD5-AS1 in doxorubicin-resistance in osteosarcoma remains to be illucidated. Quantitative real-time PCR (qRT-PCR) and western blot analysis (WB) were used to measure the expression of FGD5-AS1, miR-154-5p, WNT5A and autophagy proteins. MTT assay was used to assess cell viability and transwell assay was performed to evaluate migration. A nude mouse xenograft model was developed to verify the function of FGD5-AS1 in vivo. FGD5-AS1was upregulated in doxorubicin-resistant (DXR) osteosarcoma cells. Knockdown of FGD5-AS1 suppressed osteosarcoma cell proliferation, migration, and autophagy. FGD5-AS1 upregulated WNT5A expression via sponging miR-154-5p. Furthermore, FGD5-AS1 enhanced osteosarcoma cell chemotherapy resistance through upregulation of WNT5A by inhibiting miR-154-5p. Suppression of FGD5-AS1 significantly suppressed tumor growth in nude mice. FGD5-AS1 may promote chemoresistance through WNT5A-induced autophagy by sponging miR-154-5p in osteosarcoma cells.

Functions of Small Non-Coding RNAs in Salmonella-Host Interactions.

Simple SummaryIn the process of infecting the host, Salmonella senses and adapts to the environment within the host, breaks through the host’s defense system, and survives and multiplies in the host cell. As a class of universal regulators encoded in intergenic space, an increasing number of small non-coding RNAs (sRNAs) have been found to be involved in a series of processes during Salmonella infection, and they play an important role in interactions with the host cell. In this review, we discuss how sRNAs help Salmonella resist acidic environmental stress by regulating acid resistance genes and modulate adhesion and invasion to non-phagocytic cells by regulating virulent genes such as fimbrial subunits and outer membrane proteins. In addition, sRNAs help Salmonella adapt to oxidative stress within host cells and promote survival within macrophages. Although the function of a variety of sRNAs has been studied during host–Salmonella interactions, many of sRNAs’ functions remain to be discovered.Salmonella species infect hosts by entering phagocytic and non-phagocytic cells, causing diverse disease symptoms, such as fever, gastroenteritis, and even death. Therefore, Salmonella has attracted much attention. Many factors are involved in pathogenesis, for example, the capsule, enterotoxins, Salmonella pathogenicity islands (SPIs), and corresponding regulators. These factors are all traditional proteins associated with virulence and regulation. Recently, small non-coding RNAs (sRNAs) have also been reported to function as critical regulators. Salmonella has become a model organism for studying sRNAs. sRNAs regulate gene expression by imperfect base-pairing with targets at the post-transcriptional level. sRNAs are involved in diverse biological processes, such as virulence, substance metabolism, and adaptation to stress environments. Although some studies have reported the crucial roles of sRNAs in regulating host–pathogen interactions, the function of sRNAs in host–Salmonella interactions has rarely been reviewed. Here, we review the functions of sRNAs during the infection of host cells by Salmonella, aiming to deepen our understanding of sRNA functions and the pathogenic mechanism of Salmonella.

Integrative Investigation of Root-Related mRNAs, lncRNAs and circRNAs of "Muscat Hamburg" (Vitis vinifera L.) Grapevine in Response to Root Restriction through Transcriptomic Analyses.

Root restriction is a physical and ecological cultivation mode which restricts plant roots into a limited container to regulate vegetative and reproduction growth by reshaping root architecture. However, little is known about related molecular mechanisms. To uncover the root-related regulatory network of endogenous RNAs under root restriction cultivation (referred to RR), transcriptome-wide analyses of mRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) involved in root development were performed. During root development, RR treatment had a positive effect on root weight, typically, young roots were significantly higher than conventional cultivation (referred to NR) treatment, suggesting that root architecture reconstruction under RR was attributed to the vigorous induction into lateral roots. Furthermore, a total of 26,588 mRNAs, 1971 lncRNAs, and 2615 circRNAs were identified in root of annual “Muscat Hamburg” grapevine by the transcriptomic analyses. The expression profile of mRNAs, lncRNAs and circRNA were further confirmed by the quantitative real-time PCR (RT-qPCR). Gene ontology enrichment analysis showed that a majority of the differentially expressed mRNAs, lncRNAs and circRNAs were enriched into the categories of cellular process, metabolic process, cell part, binding, and catalytic activity. In addition, the regulatory network of endogenous RNAs was then constructed by the prediction of lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA network, implying that these RNAs play significant regulatory roles for root architecture shaping in response to root restriction. Our results, for the first time, the regulatory network of competitive endogenous RNAs (ceRNAs) functions of lncRNA and circRNA was integrated, and a basis for studying the potential functions of non-coding RNAs (ncRNAs) during root development of grapevine was provided.

PRR7-AS1 Correlates with Immune Cell Infiltration and Is a Diagnostic and Prognostic Marker for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a highly aggressive malignant disease, and numerous studies have shown that certain functional long noncoding RNAs (lncRNAs) are implicated in the progression of several cancers. The purpose of the research was to determine, using a database, bioinformatics, and statistical analysis, whether or not lncRNA PRR7-AS1 (PRR7-AS1) was related to HCC. TCGA datasets were used to conduct research on the PRR7-AS1 expression pattern in HCC. In order to evaluate the efficacy of GIHCG as a prognostic tool, both survival and Cox regression analyses were carried out. Furthermore, an investigation of the connection between the expression of PRR7-AS1 and immune infiltration in HCC was carried out. In this study, we identified 125 lncRNAs that were significantly dysregulated in HCC and were associated with long-term survival. Among the above 125 lncRNAs, our attention focused on PRR7-AS1. We found that PRR7-AS1 expressions were distinctly overexpressed in HCC samples compared with nontumor samples. ROC assays revealed that PRR7-AS1 effectively differentiated HCC specimens from normal tissues with an AUC of 0.875 (95% CI: 0.840 to 0.911). Moreover, the high PRR7-AS1 expression was associated with advanced clinical stage and poor prognosis of HCC patients. Importantly, the multivariate Cox proportional hazards model suggested that up-expression of PRR7-AS1 was an independent prognostic marker indicating shorter overall survival and disease-specific survival for HCC patients. Finally, we found that PRR7-AS1 expression was associated with the expression of NK CD56bright cells, Th2 cells, TFH, macrophages, Th1 cells, aDC, T helper cells, cytotoxic cells, DC, Tgd, neutrophils, and Th17 cells. Overall, the results of our study show that PRR7-AS1 was a biomarker that could be utilized to predict the prognosis of HCC patients and was linked to the infiltration of immune cells in HCC.