Role Of Long Non-coding RNAs Research Articles

LncRNAs and CircRNAs in Endoplasmic Reticulum Stress: A Promising Target for Cardiovascular Disease?

The endoplasmic reticulum (ER) is a principal subcellular organelle responsible for protein quality control in the secretory pathway, preventing protein misfolding and aggregation. Failure of protein quality control in the ER triggers several molecular mechanisms such as ER-associated degradation (ERAD), the unfolded protein response (UPR) or reticulophagy, which are activated upon ER stress (ERS) to re-establish protein homeostasis by transcriptionally and translationally regulated complex signalling pathways. However, maintenance over time of ERS leads to apoptosis if such stress cannot be alleviated. The presence of abnormal protein aggregates results in loss of cardiomyocyte protein homeostasis, which in turn results in several cardiovascular diseases such as dilated cardiomyopathy (DCM) or myocardial infarction (MI). The influence of a non-coding genome in the maintenance of proper cardiomyocyte homeostasis has been widely proven. To date, the impact of microRNAs in molecular mechanisms orchestrating ER stress response has been widely described. However, the role of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) is just beginning to be addressed given the potential role of these RNA classes as therapeutic molecules. Here, we provide a current state-of-the-art review of the roles of distinct lncRNAs and circRNAs in the modulation of ERS and UPR and their impact in cardiovascular diseases.

The Role of Long Noncoding RNAs in Endometriosis Progression.

Endometriosis (EMs) is a common gynecological disease with an increasing incidence in recent years. Because of the lack of specific molecular biological indicators in clinical practice, diagnosis is often delayed and the quality of life of patients is seriously reduced. Therefore, the discovery of effective molecular biomarkers is crucial for the early diagnosis and treatment of EMs patients. With the development of high-throughput sequencing technology, the mechanism of lncRNAs in EMs has been increasingly confirmed experimentally. This article summarizes the biological characteristics and functions of EMs-related lncRNAs, and introduces the mechanisms of EMs-related lncRNAs in the context of ceRNAs, in exosomes, under hypoxic conditions, and related antisense RNAs. The mechanism of the most popular imprinted gene H19 and metastasis-associated lung adenocarcinoma transcript 1 in EMs is then introduced. Finally, we explore the challenges of molecular biomarker EMs-related lncRNAs in the diagnosis and treatment of EMs, anticipating their potential value in clinical applications.

A novel trans-acting lncRNA of ACTG1 that induces the remodeling of ovarian follicles

Previous studies have implicated the attractive role of long noncoding RNAs (lncRNAs) in the remodeling of mammalian tissues. The migration of granulosa cells (GCs), which are the main supporting cells in ovarian follicles, stimulates the follicular remodeling. Here, with the cultured GCs as the follicular model, the actin gamma 1 (ACTG1) was observed to significantly promote the migration and proliferation while inhibit the apoptosis of GCs, suggesting that ACTG1 was required for ovarian remodeling. Moreover, we identified the trans-regulatory lncRNA of ACTG1 (TRLA), which was epigenetically targeted by histone H3 lysine 4 acetylation (H3K4ac). Mechanistically, the 2–375 nt of TRLA bound to ACTG1's mRNA to increase the expression of ACTG1. Furthermore, TRLA facilitated the migration and proliferation while inhibited the apoptosis of GCs, thereby accelerating follicular remodeling. Besides, TRLA acted as a ceRNA for miR-26a to increase the expression of high-mobility group AT-hook 1 (HMGA1). Collectively, TRLA induces the remodeling of ovarian follicles via complementary to ACTG1's mRNA and regulating miR-26a/HMGA1 axis in GCs. These observations revealed a novel and promising trans-acting lncRNA mechanism mediated by H3K4ac, and TRLA might be a new target to restore follicular remodeling and development.

The role of long non-coding RNAs in the development of adipose cells.

In recent times, the rising prevalence of obesity and its associated comorbidities have had a severe impact on human health and social progress. Therefore, scientists are delving deeper into the pathogenesis of obesity, exploring the role of non-coding RNAs. Long non-coding RNAs (lncRNAs), once regarded as mere "noise" during genome transcription, have now been confirmed through numerous studies to regulate gene expression and contribute to the occurrence and progression of several human diseases. LncRNAs can interact with protein, DNA, and RNA, respectively, and participate in regulating gene expression by modulating the levels of visible modification, transcription, post-transcription, and biological environment. Increasingly, researchers have established the involvement of lncRNAs in regulating adipogenesis, development, and energy metabolism of adipose tissue (white and brown fat). In this article, we present a literature review of the role of lncRNAs in the development of adipose cells.

Identification and profiling of long non-coding RNAs during molt cycle: An involvement of lnc1182 in the molt of white shrimp, Litopenaeus vannamei

Molt is an essential physiological process for crustacean growth. It is known to be controlled by factors such as hormones and steroids, but the role of long non-coding RNA (lncRNA), a potential regulatory molecule, has not been studied. In this study, we investigated the role of lncRNA in the molt process of white shrimp, Litopenaeus vannamei. The 9437 of 58,142 unigenes of de novo assembled transcriptome were identified as putative lncRNAs, and 768 lncRNAs were differentially expressed during molt cycles. Five differentially expressed lncRNAs were selected to determine their expressions in different tissues and molt stages. Most were expressed more in gills and epidermis than other tissues. Expressions of lnc1182 and lnc336 significantly decreased during premolt stages and increased at postmolt in gills and epidermis, while lnc179 expression increased during premolt stages. RNA interference was used to investigate the role of lnc1182 in the molt process. The molt of lnc1182 knockdown shrimp progressed to early premolt faster than shrimp injected with dsGFP, and also shortened molt duration. In addition, total sugar level in hemolymph was higher in the lnc1182 knockdown shrimp than the control shrimp, whereas gill Na+/K+ ATPase activity, total hemocyte count, and expression of molt-inhibiting hormone (MIH) were not changed. These suggested that lnc1182 is likely involved in the control of sugar metabolism during molting but not in ion exchange activity and MIH expression. Furthermore, lnc1182 and 20-HE probably regulated each other. RNA sequencing was used to investigate the set of genes associated with lnc1182. Fifty-five transcripts were differentially expressed in gills of lnc1182 knockdown shrimp. Expressions of candidate metabolism and immune-related genes were validated for their differential expressions in lnc1182 knockdown shrimp. Our work produced lncRNA profiles and indicated possible functions of lnc1182 in metabolism and immunity during the molt cycle in shrimp.

Novel sights on therapeutic, prognostic, and diagnostics aspects of non-coding RNAs in glioblastoma multiforme.

Glioblastoma Multiforme (GBM) is the primary brain tumor and accounts for 200,000 deaths each year worldwide. The standard therapy includes surgical resection followed by temozolomide (TMZ)-based chemotherapy and radiotherapy. The survival period of GBM patients is only 12-15months. Therefore, novel treatment modalities for GBM treatment are urgently needed. Mounting evidence reveals that non-coding RNAs (ncRNAs) were involved in regulating gene expression, the pathophysiology of GBM, and enhancing therapeutic outcomes. The combinatory use of ncRNAs, chemotherapeutic drugs, and tumor suppressor gene expression induction might provide an innovative, alternative therapeutic approach for managing GBM. Studies have highlighted the role of Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in prognosis and diagnosis. Dysregulation of ncRNAs is observed in virtually all tumor types, including GBMs. Studies have also indicated the blood-brain barrier (BBB) as a crucial factor that hinders chemotherapy. Although several nanoparticle-mediated drug deliveries were degrading effectively against GBM in vitro conditions. However, the potential to cross the BBB and optimum delivery of oligonucleotide RNA into GBM cells in the brain is currently under intense clinical trials. Despite several advances in molecular pathogenesis, GBM remains resistant to chemo and radiotherapy. Targeted therapies have less clinical benefit due to high genetic heterogeneity and activation of alternative pathways. Thus, identifying GBM-specific prognostic pathways, essential genes, and genomic aberrations provide several potential benefits as subtypes of GBM. Also, these approaches will provide insights into new strategies to overcome the heterogenous nature of GBM, which will eventually lead to successful therapeutic interventions toward precision medicine and precision oncology.

Downregulation of the long noncoding RNA DSCR9 (Down syndrome critical region 9) delays breast cancer progression by modulating microRNA-504-5p-dependent G protein-coupled receptor 65.

Possible roles of long noncoding RNAs (lncRNAs) in cancer stem cells (CSCs) have often been reported. Here, we focused on the regulatory function of the lncRNA Down syndrome critical region 9 (DSCR9) in breast cancer stem cells (BCSCs). Through bioinformatics analysis, DSCR9, microRNA-504-5p (miR-504-5p), and G protein-coupled receptor 65 (GPR65) were identified as targets implicated in breast cancer development. Then, clinical tissue samples, breast cancer cells, and isolated BCSCs were used to determine the expression of DSCR9, miR-504-5p, and GPR65. The results confirmed the overexpression of DSCR9 and GPR65 but low expression of miR-504-5p in breast cancer tissues and cells as well as in BCSCs. Following mechanistic investigation, it was found that DSCR9 targeted miR-504-5p, and that silencing DSCR9 inhibited the proliferation of BCSCs by elevating the expression of miR-504-5p. Additionally, miR-504-5p targeted GPR65 and inhibited its expression. Moreover, GPR65 activated the MEK/ERK signaling pathway to regulate BCSC proliferation. Finally, animal study verified that depletion of DSCR9 inhibited the proliferation of BCSCs in vivo and that BCSC proliferation was restored by overexpression of GPR65. Altogether, our findings revealed that DSCR9 elevated GPR65 expression by targeting miR-504-5p to exacerbate breast cancer, highlighting a new treatment modality for breast cancer.

GATA6-AS1 via Sponging miR-543 to Regulate PTEN/AKT Signaling Axis Suppresses Cell Proliferation and Migration in Gastric Cancer.

Gastric cancer (GC) is one of the most common and lethal cancers worldwide. In view of the prominent roles of long noncoding RNAs (lncRNAs) in cancers, we investigated the specific role and underlying mechanism of GATA binding protein 6 antisense RNA 1 (GATA6-AS1) in GC. Quantitative real-time polymerase chain reaction (qRT-PCR) detected GATA6-AS1 expression in GC cell lines. Functional assays were conducted to explore the role of GATA6-AS1 in GC. Furthermore, mechanism investigations were implemented to uncover the interaction among GATA6-AS1, microRNA-543 (miR-543), and phosphatase and tensin homolog (PTEN). In the present study, it was found that GATA6-AS1 expression is significantly downregulated in GC cell lines. Functionally, GATA6-AS1 markedly suppresses GC cell growth and migration in vitro and in vivo tumorigenesis. Besides tumor suppressor, GATA6-AS1 serves as a miR-543 sponge. Specifically speaking, GATA6-AS1 acts as a competing endogenous RNA (ceRNA) of miR-543 to upregulate the expression of PTEN, thus inactivating AKT signaling pathway to inhibit GC progression. In conclusion, this study has manifested that GATA6-AS1 inhibits GC cell proliferation and migration as a sponge of miR-543 by regulating PTEN/AKT signaling axis, offering new perspective into developing novel GC therapies.

High-throughput transcriptome sequencing reveals the critical role of long non-coding RNA Gm14376 in the occurrence of neuropathic pain

Long noncoding RNAs (lncRNAs) have been suggested as important regulators in neuropathic pain. Our study aims to explore the possible molecular mechanism underlying the role of long non-coding RNA (lncRNA) Gm14376 in neuropathic pain in mice by high-throughput transcriptome sequencing. A mouse model of spared nerve injury (SNI) was constructed for mechanical, thermal and spontaneous pain testing. Transcriptomic changes in lncRNAs and mRNAs in the dorsal root ganglion (DRG) of SNI mice were analyzed using RNA-sequencing techniques in conjunction with public data analysis. AAV5 viral vector was constructed to assess the effect of Gm14376 on SNI-induced pain hypersensitivity and inflammatory response. Cis-target genes of Gm14376 were obtained and the functions of Gm14376 were analyzed by GO and KEGG pathway enrichment analyses. Results from bioinformatic analysis identified a conserved Gm14376, which was up-regulated in the DRG of SNI mice, specifically in response to nerve injury. Overexpression of Gm14376 in DRG induced neuropathic pain-like symptoms in mice. Furthermore, the functions of Gm14376 were related to the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and fibroblast growth factor 3 (Fgf3) was identified as the cis-target gene of Gm14376. Gm14376 could directly up-regulate Fgf3 expression to activate the PI3K/Akt pathway, which alleviated pain hypersensitivity to mechanical and thermal stimuli and reduced the release of inflammatory factors in SNI mice. From our data, we conclude that SNI-induced up-regulation of Gm14376 expression in DRG activates the PI3K/Akt pathway through up-regulation of Fgf3 expression, thereby promoting the development of neuropathic pain in mice.

Long Noncoding RNA UCA1 Correlates With Electropathology in Patients With Atrial Fibrillation

BackgroundPerpetuation of atrial fibrillation (AF) is rooted in derailment of molecular proteostasis pathways that cause electrical conduction disorders that drive AF. Emerging evidence indicates a role for long noncoding RNAs (lncRNAs) in the pathophysiology of cardiac diseases, including AF. ObjectivesIn the present study, the authors explored the association between 3 cardiac lncRNAs and the degree of electropathology. MethodsPatients had paroxysmal AF (ParAF) (n = 59), persistent AF (PerAF) (n = 56), or normal sinus rhythm without a history of AF (SR) (n = 70). The relative expression levels of urothelial carcinoma–associated 1 (UCA1), OXCT1-AS1 (SARRAH), and the mitochondrial lncRNA uc022bqs.q (LIPCAR) were measured by means of quantitative reverse-transcription polymerase chain reaction in the right atrial appendage (RAA) or serum (or both). A selection of the patients was subjected to high-resolution epicardial mapping to evaluate electrophysiologic features during SR. ResultsThe expression levels of SARRAH and LIPCAR were decreased in RAAs of all AF patients compared with SR. Also, in RAAs, UCA1 levels significantly correlated with the percentage of conduction block and delay, and inversely with conduction velocity, indicating that UCA1 levels in RAA reflect the degree of electrophysiologic disorders. Moreover, in serum samples, SARRAH and UCA1 levels were increased in the total AF group and ParAF patients compared with SR. ConclusionsLncRNAs SARRAH and LIPCAR are reduced in RAA of AF patients, and UCA1 levels correlate with electrophysiologic conduction abnormalities. Thus, RAA UCA1 levels may aid staging of electropathology severity and act as a patient-tailored bioelectrical fingerprint.

A CRISPR-Cas9 mutation in sox9b long intergenic noncoding RNA (slincR) affects zebrafish development, behavior, and regeneration.

The role of long noncoding RNAs (lncRNAs) regulators of toxicological responses to environmental chemicals is gaining prominence. Previously, our laboratory discovered an lncRNA, sox9b long intergenic noncoding RNA (slincR), that is activated by multiple ligands of aryl hydrocarbon receptor (AHR). Within this study, we designed a CRISPR-Cas9-mediated slincR zebrafish mutant line to better understand its biological function in presence or absence of a model AHR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The slincRosu3 line contains an 18 bp insertion within the slincR sequence that changes its predicted mRNA secondary structure. Toxicological profiling showed that slincRosu3 is equally or more sensitive to TCDD for morphological and behavioral phenotypes. Embryonic mRNA-sequencing showed differential responses of 499 or 908 genes in slincRosu3 in absence or presence of TCDD Specifically, unexposed slincRosu3 embryos showed disruptions in metabolic pathways, suggesting an endogenous role for slincR. slincRosu3 embryos also had repressed mRNA levels of sox9b-a transcription factor that slincR is known to negatively regulate. Hence, we studied cartilage development and regenerative capacity-both processes partially regulated by sox9b. Cartilage development was disrupted in slincRosu3 embryos both in presence and absence of TCDD. slincRosu3 embryos also displayed a lack of regenerative capacity of amputated tail fins, accompanied by a lack of cell proliferation. In summary, using a novel slincR mutant line, we show that a mutation in slincR can have widespread impacts on gene expression and structural development endogenously and limited, but significant impacts in presence of AHR induction that further highlights its importance in the developmental process.

Competing endogenous RNA analysis identified lncRNA DSCR9 as a novel prognostic biomarker associated with metastasis and tumor microenvironment in renal cell carcinoma.

Distant metastasis is the main cause of death in patients with clear cell renal carcinoma (ccRCC). The dysregulation of the tumor microenvironment is responsible for tumorigenesis and metastasis in ccRCC. The role of long non-coding RNAs in the tumor immune of ccRCC remains unclear. The present study screened differentially expressed protein-coding genes and non-coding genes between ccRCC and normal tissues based on three datasets. The commonly deregulated genes were used to identify distant metastasis-related long non-coding RNAs (lncRNAs) and prognostic lncRNAs. Pearson correlation analysis was used to identify immune-related lncRNAs. A competing endogenous RNA network was constructed and hub lncRNAs were identified. A total of 1650 coding genes, 821 lncRNAs and 62 miRNAs were commonly deregulated in the three datasets. A total of 408 lncRNAs associated with the overall survival of patients with ccRCC were identified. Among them, 82 lncRNAs were distant metastasis-related. Further analysis identified 52 lncRNAs associated with the immune pathway. Functional analyses concordantly demonstrated the role of the 52 lncRNAs in metastasis and tumor immunology. The ceRNA network analysis indicated lncRNA DSCR9 as the key lncRNA regulator. Univariate and multivariate analysis in two independent cohorts validated that DSCR9 could be an independent risk factor for the progression-free survival of patients with ccRCC. Further analyses indicated that DSCR9 might be associated with the immunotherapeutic response. reverse transcription-quantitative PCR demonstrated that the RNA expression level of DSCR9 was upregulated in ccRCC compared with normal kidney samples. The present study demonstrated the potential of LncRNA DSCR9 in assessing the prognosis and developing future immunotherapy for patients with metastatic ccRCC.

Long noncoding RNA #61 exerts a broad anti-influenza a virus effect by its long arm rings

Emerging evidence has demonstrated the critical role of long noncoding RNAs (lncRNAs) in regulating gene expression. However, the functional significance and mechanisms underlying influenza A virus (IAV)-host lncRNA interactions are still elusive. Here, we identified a functional lncRNA, LncRNA#61, as a broad anti-IAV factor. LncRNA#61 is highly upregulated by different subtypes of IAV, including human H1N1 virus and avian H5N1 and H7N9 viruses. Furthermore, nuclear-enriched LncRNA#61 can translocate from the nucleus to the cytoplasm soon after IAV infection. Forced LncRNA#61 expression dramatically impedes viral replication of various subtypes of IAV, including human H1N1 virus and avian H3N2/N8, H4N6, H5N1, H6N2/N8, H7N9, H8N4, H10N3, H11N2/N6/N9 viruses. Conversely, abolishing LncRNA#61 expression substantially favored viral replication. More importantly, LncRNA#61 delivered by the lipid nanoparticle (LNP)-encapsulated strategy shows good performance in restraining viral replication in mice. Interestingly, LncRNA#61 is involved in multiple steps of the viral replication cycle, including virus entry, viral RNA synthesis and the virus release period. Mechanistically, the four long ring arms of LncRNA#61 mainly mediate its broad antiviral effect and contribute to its inhibition of viral polymerase activity and nuclear aggregation of key polymerase components. Therefore, we defined LncRNA#61 as a potential broad-spectrum antiviral factor for IAV. Our study further extends our understanding of the stunning and unanticipated biology of lncRNAs as well as their close interaction with IAV, providing valuable clues for developing novel broad anti-IAV therapeutics targeting host lncRNAs.

Long non-coding RNA TLR8-AS1 induces preeclampsia through increasing TLR8/STAT1 axis.

Our current study tried to assay the role of long noncoding RNAs (lncRNAs) TLR8-AS1 in regulating preeclampsia. TLR8-AS1 expression was examined in the clinical placental tissues of preeclampsia patients and the trophoblast cells induced by lipopolysaccharide (LPS). Then, different lentivirus was infected into trophoblast cells to study the role of TLR8-AS1 in cell functions. Furthermore, interactions among TLR8-AS1, signal transducer and activator of transcription 1 (STAT1) and toll-like receptor 8 (TLR8) were determined. A rat model of preeclampsia induced by N(omega)-nitro-L-arginine methyl ester was developed to validate the in-vitro findings. High expression of TLR8-AS1 was detected in placental tissues of preeclampsia patients and LPS-induced trophoblast cells. In addition, overexpression of TLR8-AS1 arrested the proliferation, migration and invasion of trophoblast cells, which was related to the upregulation of TLR8 expression. Mechanistically, TLR8-AS1 recruited STAT1 to bind to the TLR8 promoter region, and thus promoted the transcription of TLR8. Meanwhile, overexpression of TLR8-AS1 was shown to aggravate preeclampsia by elevating TLR8 in vivo . Our study confirmed that TLR8-AS1 aggravated the progression of preeclampsia through increasing the expression of STAT1 and TLR8.

Functional inference of long non-coding RNAs through exploration of highly conserved regions.

Background: Long non-coding RNAs (lncRNAs), which are generally less functionally characterized or less annotated, evolve more rapidly than mRNAs and substantially possess fewer sequence conservation patterns than protein-coding genes across divergent species. People assume that the functional inference could be conducted on the evolutionarily conserved long non-coding RNAs as they are most likely to be functional. In the past decades, substantial progress has been made in discussions on the evolutionary conservation of non-coding genomic regions from multiple perspectives. However, understanding their conservation and the functions associated with sequence conservation in relation to further corresponding phenotypic variability or disorders still remains incomplete. Results: Accordingly, we determined a highly conserved region (HCR) to verify the sequence conservation among long non-coding RNAs and systematically profiled homologous long non-coding RNA clusters in humans and mice based on the detection of highly conserved regions. Moreover, according to homolog clustering, we explored the potential function inference via highly conserved regions on representative long non-coding RNAs. On lncRNA XACT, we investigated the potential functional competence between XACT and lncRNA XIST by recruiting miRNA-29a, regulating the downstream target genes. In addition, on lncRNA LINC00461, we examined the interaction relationship between LINC00461 and SND1. This interaction or association may be perturbed during the progression of glioma. In addition, we have constructed a website with user-friendly web interfaces for searching, analyzing, and downloading to present the homologous clusters of humans and mice. Conclusion: Collectively, homolog clustering via the highly conserved region definition and detection on long non-coding RNAs, as well as the functional explorations on representative sequences in our research, would provide new evidence for the potential function of long non-coding RNAs. Our results on the remarkable roles of long non-coding RNAs would presumably provide a new theoretical basis and candidate diagnostic indicators for tumors.

LncRNA CROCCP2/miR-5584-5p/BIRC5 network activates apoptosis to inhibit glioma development

Objective: To detect the role of long non-coding RNA (lncRNA) CROCC Pseudogene 2 (CROCCP2)/miR-5584-5p /Baculoviral IAP Repeat Containing 5 (BIRC5) network in glioma growth. Methods: The Cancer Genome Atlas (TCGA) database was accessed to obtain the gene datasets associated with glioma growth. Bioinformatics techniques was employed to analyze the key network and construct the regulatory network of lncRNA CROCCP2/miR-5584-5p targeting BIRC5. Subsequently, the quantitative Polymerase Chain Reaction (qPCR) experiment was conducted to validate the expression levels of LncRNA CROCCP2, miR-5584-5p, and BIRC5 in both glioma tissues and normal brain tissues. Furthermore, we harnessed RNA interference technology to knock down BIRC5 in U251 cells, and flow cytometry was utilized to assess cell apoptosis. Results: LncRNA CROCCP2 is implicated in the binding of miR-5584-5p, and targeting BIRC5. PCR analysis revealed an elevated expression level of CROCCP2 and BIRC5 in glioma tissues, accompanied by a low expression of miR-5584-5p. Moreover, knockdown of BIRC5 results in an induction of apoptosis. Conclusions: LncRNA CROCCP2 could absorb miR-5584-5p targeting BIRC5 to activate cell apoptosis, so as to inhibit glioma development.

Roles of long non-coding RNAs in plant immunity.

Robust plant immune systems are fine-tuned by both protein-coding genes and non-coding RNAs. Long non-coding RNAs (lncRNAs) refer to RNAs with a length of more than 200 nt and usually do not have protein-coding function and do not belong to any other well-known non-coding RNA types. The non-protein-coding, low expression, and non-conservative characteristics of lncRNAs restrict their recognition. Although studies of lncRNAs in plants are in the early stage, emerging studies have shown that plants employ lncRNAs to regulate plant immunity. Moreover, in response to stresses, numerous lncRNAs are differentially expressed, which manifests the actions of low-expressed lncRNAs and makes plant-microbe/insect interactions a convenient system to study the functions of lncRNAs. Here, we summarize the current advances in plant lncRNAs, discuss their regulatory effects in different stages of plant immunity, and highlight their roles in diverse plant-microbe/insect interactions. These insights will not only strengthen our understanding of the roles and actions of lncRNAs in plant-microbe/insect interactions but also provide novel insight into plant immune responses and a basis for further research in this field.

A novel lncRNA SNHG29 regulates EP300- related histone acetylation modification and inhibits FLT3-ITD AML development.

Internal tandem duplication (ITD) mutations within the FMS-like tyrosine kinase-3 (FLT3) occur in up to 25% of acute myeloid leukemia (AML) patients and indicate a very poor prognosis. The role of long noncoding RNAs (lncRNAs) in FLT3-ITD AML progression remains unexplored. We identified a novel lncRNA, SNHG29, whose expression is specifically regulated by the FLT3-STAT5 signaling pathway and is abnormally down-regulated in FLT3-ITD AML cell lines. SNHG29 functions as a tumor suppressor, significantly inhibiting FLT3-ITD AML cell proliferation and decreasing sensitivity to cytarabine in vitro and in vivo models. Mechanistically, we demonstrated that SNHG29's molecular mechanism is EP300-binding dependent and identified the EP300-interacting region of SNHG29. SNHG29 modulates genome-wide EP300 genomic binding, affecting EP300-mediated histone modification and consequently influencing the expression of varies downstream AML-associated genes. Our study uncovers a novel molecular mechanism for SNHG29 in mediating FLT3-ITD AML biological behaviors through epigenetic modification, suggesting that SNHG29 could be a potential therapeutic target for FLT3-ITD AML.

Critical role of long non-coding RNAs in excessive erythropoietic response in Monge's disease

Excessive erythrocytosis (EE) is a major hallmark of patients suffering from chronic mountain sickness (CMS, Monge’s disease) and is responsible for major morbidity and even mortality in early adulthood. We took advantage of unique populations, one living at high altitude (Peru) showing EE, while another population, at the same altitude and region, shows no evidence of EE (non-CMS). We have built an in-vitro human iPS-derived model system to study the genetic and epigenetic mechanisms related to pathology of excessive erythropoetic response in these Monge's disease patients. Through RNA-seq, we identified and validated the function of a group of long non-coding RNA (lncRNAs) that regulate erythropoiesis in Monge’s disease. Among the lncRNAs, we found that LINC02228 specifically played a critical role in erythropoiesis the CMS cells and non-CMS based on our functional assays in our in-vitro model systems. We observed that LINC02228 has a huge impact on erythriod colony production (>50% reduction in colonies p<0.001 with the control vs LINC02228-KD). Furthermore, we have also assessed the downstream target genes for these lncRNA (Eg. CSNK2B) and mechanism(s) of erythropoetic regulation by these lncRNAs and found an important role and mediation of erythropoetic transcriptional factor GATA1. We conclude that LINC02228 mediate erythropoesis in Monge's diseases through critical downstream effectors (CSNK2B and GATA1). NIH This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Role of long non-coding RNAs in pancreatic cancer pathogenesis and treatment resistance- A review.

Pancreatic cancer (PC) is one of the deadliest cancers associated with poor prognosis. The lack of reliable means of early cancer detection contributes to this disease's dismal prognosis. Long non-coding RNAs (LncRNAs) are protein-free RNAs produced by genome transcription; they play critical roles in gene expression regulation, epigenetic modification, cell proliferation, differentiation, and reproduction. Recent research has shown that lncRNAs play important regulatory roles in PC behaviors, in addition to their recently found functions. Several in-depth investigations have shown that lncRNAs are strongly linked to PC development and progression. Here, we discuss how lncRNAs, which are often overlooked, play many roles as regulators in the molecular mechanism underlying PC. This review also discusses the involved LncRNAs in PC pathogenesis and treatment resistance.