Role Of Long Non-coding RNAs Research Articles

Vascular dysfunction in COVID-19 patients: update on SARS-CoV-2 infection of endothelial cells and the role of long non-coding RNAs.

Although COVID-19 is primarily a respiratory disease, it may affect also the cardiovascular system. COVID-19 patients with cardiovascular disorder (CVD) develop a more severe disease course with a significantly higher mortality rate than non-CVD patients. A common denominator of CVD is the dysfunction of endothelial cells (ECs), increased vascular permeability, endothelial-to-mesenchymal transition, coagulation, and inflammation. It has been assumed that clinical complications in COVID-19 patients suffering from CVD are caused by SARS-CoV-2 infection of ECs through the angiotensin-converting enzyme 2 (ACE2) receptor and the cellular transmembrane protease serine 2 (TMPRSS2) and the consequent dysfunction of the infected vascular cells. Meanwhile, other factors associated with SARS-CoV-2 entry into the host cells have been described, including disintegrin and metalloproteinase domain-containing protein 17 (ADAM17), the C-type lectin CD209L or heparan sulfate proteoglycans (HSPG). Here, we discuss the current data about the putative entry of SARS-CoV-2 into endothelial and smooth muscle cells. Furthermore, we highlight the potential role of long non-coding RNAs (lncRNAs) affecting vascular permeability in CVD, a process that might exacerbate disease in COVID-19 patients.

Differentially expressed long noncoding RNAs and mRNAs in PC12 cells under lysophosphatidylcholine stimulation

Lysophosphatidylcholine (LPC) was previously found to show neuroprotective effect on nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) induced signalings. Also, numerous studies reported the emerging roles of long noncoding RNAs (LncRNAs) involved in neurodegenerative disease. However, the biological mechanism of LPC and expression profile of lncRNAs has not been reported. Here, lncRNAs in PC12 cells under LPC and NGF treatment were analyzed using high throughput sequencing technology for the first time. We identified 564 annotated and 1077 novel lncRNAs in PC12 cells. Among them, 121 lncRNAs were differentially expressed in the PC12 cells under LPC stimulation. KEGG analysis showed that differentially expressed mRNAs co-expressed with lncRNAs mainly enriched in ribosome, oxidative phosphorylation, Parkinson’s disease, Huntington’s disease and Alzheimer’s disease etc. LncRNA-mRNA network analysis showed that lncRNA ENSRNOT00000082515 had interactions with 626 different mRNAs suggesting that lncRNA ENSRNOT00000082515 probably play vital role. Finally, sequencing data were validated by qRT-PCR for ENSRNOT00000084874, ENSRNOT00000082515, LNC_001033 forward Fgf18, Vcam1, and Pck2.

Inferring bona fide Differentially Expressed Genes and Their Variants Associated with Vitamin K Deficiency Using a Systems Genetics Approach.

Systems genetics is key for integrating a large number of variants associated with diseases. Vitamin K (VK) is one of the scarcely studied disease conditions. In this work, we ascertained the differentially expressed genes (DEGs) and variants associated with individual subpopulations of VK disease phenotypes, viz., myocardial infarction, renal failure and prostate cancer. We sought to ask whether or not any DEGs harbor pathogenic variants common in these conditions, attempt to bridge the gap in finding characteristic biomarkers and discuss the role of long noncoding RNAs (lncRNAs) in the biogenesis of VK deficiencies.

The role of long noncoding RNAs in therapeutic resistance in cervical cancer.

Cervical cancer is one of the common tumors and often causes cancer-related death in women. Chemotherapy is a common cancer therapy, which displays a pivotal clinical benefit for cancer patients. However, chemoresistance becomes a big obstacle for failure of treatment in cancer patients. Recently, long noncoding RNAs (lncRNAs) have been identified to regulate drug resistance in human cancers, including cervical cancer. In this review, we describe the role of lncRNAs in regulation of chemotherapeutic resistance in cervical cancer. We also discuss the molecular mechanisms of lncRNA-mediated drug resistance in cervical cancer. Moreover, we describe that targeting lncRNAs could reverse drug resistance in cervical cancer. Therefore, lncRNAs could become effective therapeutic targets and chemotherapeutic sensitizers for cervical cancer patients.

Insights into the roles of long noncoding RNAs in the communication between plants and the environment.

In addition to coding proteins, RNA molecules, especially long noncoding RNAs (lncRNAs), have well-established functions in regulating gene expression. The number of studies focused on the roles played by different types of lncRNAs in a variety of plant biological processes has markedly increased. These lncRNA roles involve plant vegetative and reproductive growth and responses to biotic and abiotic stresses. In this review, we examine the classification, mechanisms, and functions of lncRNAs and then emphasize the roles played by these lncRNAs in the communication between plants and the environment mainly with respect to the following environmental factors: temperature, light, water, salt stress, and nutrient deficiencies. We also discuss the consensus among researchers and the remaining challenges and underscore the exciting ways lncRNAs may affect the biology of plants.

Effect of long noncoding RNA NONHSAT070806 on the apoptosis, proliferation, migration, invasion and tumorigenesis of bladder cancer.

Bladder cancer (BC) is the most common malignancy of the urinary tract in China, and the extent of tumor invasion negatively correlates with prognosis. The mechanism of tumor invasion in BC has been unclear until recent studies revealed the critical role of long noncoding RNAs (lncRNAs) in the proliferation and invasion of tumors. Several lncRNAs have been reported to be associated with pathogenesis in BC, but not specifically. We used a microarray to screen the candidate lncRNAs with different expressions in BC. The expression of the lncRNAs in BC tissues or cells was identified by reverse transcription polymerase chain reaction (RT-PCR) or quantitative real-time PCR (qRT-PCR), and their ectopic expressions were measured via transfection experiment. The function of the lncRNAs was investigated by flow cytometry, caspase-3 enzyme linked immunosorbent assay (ELISA), Cell Counting Kit-8 (CCK-8), wound healing, transwell and colony formation experiments in vitro and xenograft experiments in vivo. We identified a novel sense lncRNA, NONHSAT070806, that was downregulated in BC tissues and cells and negatively correlated with level of tumor invasion in patients. Furthermore, overexpression of NONHSAT070806 induced apoptosis of T24 and 5637 cells, inhibited the proliferation, migration and invasion of BC cells, and attenuated the tumorigenesis of BC cells both in vitro and in vivo. NONHSAT070806 may act as a suppressor of BC and is a potential indicator of the invasiveness of BC.

LncGBP9 knockdown alleviates myocardial inflammation and apoptosis in mice with acute viral myocarditis via suppressing NF-κB signaling pathway.

Myocardial inflammation and apoptosis are key processes in coxsackievirus B3 (CVB3)-induced acute viral myocarditis (AVMC). Accumulating evidence reveals the essential roles of long noncoding RNAs (lncRNAs) in the pathogenesis of AVMC. Here, we aimed to evaluate the biological functions of a novel lncRNA guanylate-binding protein 9 (lncGBP9) in AVMC progression and further explore its underlying mechanisms. Initially, mouse models of AVMC were constructed by CVB3 infection. The expression and localization of lncGBP9 in heart tissues were analyzed using RT-qPCR and FISH. Adeno-associated virus serotype 9 (AAV9)-mediated lncGBP9 knockdown was then employed to clarify its roles in survival, cardiac function, and myocardial inflammation and apoptosis. Moreover, the mRNA and protein levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) were detected by RT-qPCR and ELISA, and the regulation of lncGBP9 knockdown on the NF-κB signaling pathway was investigated by Western blotting. Using an in vitro model of HL-1 cardiomyocytes exposed to CVB3 infection, the effects of lncGBP9 knockdown on cell viability, inflammation, and apoptosis were further evaluated in vitro. Increased lncGBP9 expression was detected in the heart tissues of AVMC mice and CVB3-infected HL-1 cells, and was mainly located in the cytoplasm. Knockdown of lncGBP9 remarkably alleviated the severity of AVMC in CVB3-infected mice, as verified by improved cardiac function, and reduced myocardial inflammation and apoptosis. Additionally, lncGBP9 knockdown suppressed the NF-κB signaling pathway and consequently reduced productions of pro-inflammatory cytokines in vivo. In vitro functional assays further confirmed that lncGBP9 knockdown promoted cell viability, inhibited cell apoptosis, and reduced pro-inflammatory cytokines release in CVB3-infected HL-1 cells through suppressing NF-κB activation. Collectively, lncGBP9 knockdown exerts anti-inflammatory and anti-apoptotic effects in CVB3-induced AVMC, which may be mediated in part via NF-κB signaling pathway. These findings highlight lncGBP9 as an attractive target for therapeutic interventions.

Glycation-Associated Diabetic Nephropathy and the Role of Long Noncoding RNAs.

The glycation of various biomolecules is the root cause of many pathological conditions associated with diabetic nephropathy and end-stage kidney disease. Glycation imbalances metabolism and increases renal cell injury. Numerous therapeutic measures have narrowed down the adverse effects of endogenous glycation, but efficient and potent measures are miles away. Recent advances in the identification and characterization of noncoding RNAs, especially the long noncoding RNAs (lncRNAs), have opened a mammon of new biology to explore the mitigations for glycation-associated diabetic nephropathy. Furthermore, tissue-specific distribution and condition-specific expression make lncRNA a promising key for second-generation therapeutic interventions. Though the techniques to identify and exemplify noncoding RNAs are rapidly evolving, the lncRNA study encounters multiple methodological constraints. This review will discuss lncRNAs and their possible involvement in glycation and advanced glycation end products (AGEs) signaling pathways. We further highlight the possible approaches for lncRNA-based therapeutics and their working mechanism for perturbing glycation and conclude our review with lncRNAs biology-related future opportunities.

Development of genomic instability-associated long non-coding RNA signature: A prognostic risk model of clear cell renal cell carcinoma.

Renal clear cell carcinoma (ccRCC) is the most lethal of all pathological subtypes of renal cell carcinoma (RCC). Genomic instability was recently reported to be related to the occurrence and development of kidney cancer. The biological roles of long non-coding RNAs (lncRNAs) in tumorigenesis have been increasingly valued, and various lncRNAs were found to be oncogenes or cancer suppressors. Herein, we identified a novel genomic instability-associated lncRNA (GILncs) model for ccRCC patients to predict the overall survival (OS). The Cancer Genome Atlas (TCGA) database was utilized to obtain full transcriptome data, somatic mutation profiles, and clinical characteristics. The differentially expressed lncRNAs between the genome-unstable-like group (GU) and the genome-stable-like group (GS) were defined as GILncs, with |logFC| > 1 and an adjusted p-value< 0.05 for a false discovery rate. All samples were allocated into GU-like or GS-like types based on the expression of GILncs observed using hierarchical cluster analyses. A genomic instability-associated lncRNA signature (GILncSig) was constructed using parameters of the included lncRNAs. Quantitative real-time PCR analysis was used to detect the in vitro expression of the included lncRNAs. Validation of the risk model was performed by the log-rank test, time-dependent receiver operating characteristic (ROC) curves analysis, and multivariate Cox regression analysis. Forty-six lncRNAs were identified as GILncs. LINC00460, AL139351.1, and AC156455.1 were employed for GILncSig calculation based on the results of Cox analysis. GILncSig was confirmed as an independent predictor for OS of ccRCC patients. Additionally, it presented a higher efficiency and accuracy than other RCC prognostic models reported before. GILncSig score was qualified as a critical indicator, independent of other clinical factors, for prognostic prediction of ccRCC patients.

The Role of Long Noncoding RNAs on Male Infertility: A Systematic Review and In Silico Analysis.

Simple SummaryMale infertility is a health problem affecting a huge number of couples worldwide. For many years, scientists have focused on protein-coding genes to explore the causes and mechanisms of male infertility. In addition, noncoding regions that are transcribed but do not lead to protein production have also been proven to play an important role in many cellular processes and diseases. The exact role of long noncoding RNAs on male infertility is not well understood. In order to address this gap, we performed a systematic review of the literature using two databases, and then a bioinformatics analysis to identify the most important long noncoding RNAs in male infertility, as well as their mechanism of action. At first, we identified 625 articles, but after selecting some of them according to the criteria that we defined, our final sample comprised 20 articles. After analyzing them, many long noncoding RNAs were found to be deregulated in male infertility or specific subtypes of it, paving the way for a better understanding of the molecular mechanisms behind male infertility, or even for the improvement of diagnosis and therapy. Finally, an association was found between male infertility and cancer that requires further investigation in the future.Male infertility is a complex disorder affecting many couples worldwide. Long noncoding RNAs (lncRNAs) regulate important cellular processes; however, a comprehensive understanding of their role in male infertility is limited. This systematic review investigates the differential expressions of lncRNAs in male infertility or variations in lncRNA regions associated with it. The PRISMA guidelines were used to search Pubmed and Web of Science (1 June 2022). Inclusion criteria were human participants, patients diagnosed with male infertility, and English language speakers. We also performed an in silico analysis investigating lncRNAs that are reported in many subtypes of male infertility. A total of 625 articles were found, and after the screening and eligibility stages, 20 studies were included in the final sample. Many lncRNAs are deregulated in male infertility, and interactions between lncRNAs and miRNAs play an important role. However, there is a knowledge gap regarding the impact of variants found in lncRNA regions. Furthermore, eight lncRNAs were identified as differentially expressed in many subtypes of male infertility. After in silico analysis, gene ontology (GO) and KEGG enrichment analysis of the genes targeted by them revealed their association with bladder and prostate cancer. However, pathways involved in general in tumorigenesis and cancer development of all types, such as p53 pathways, apoptosis, and cell death, were also enriched, indicating a link between cancer and male infertility. This evidence, however, is preliminary. Future research is needed to explore the exact mechanism of action of the identified lncRNAs and investigate the association between male infertility and cancer.

Role of Long Non-Coding RNAs in Human-Induced Pluripotent Stem Cells Derived Megakaryocytes: A p53, HOX Antisense Intergenic RNA Myeloid 1, and miR-125b Interaction Study.

Megakaryocytes (MKs) are rare polyploid cells found in the bone marrow and produce platelets. Platelets are small cell fragments that are essential during wound healing and vascular hemostasis. In vitro differentiation of MKs from human-induced pluripotent stem cell-derived CD34+ hematopoietic stem cells (hiPSC-HSCs) could provide an alternative treatment option for thrombocytopenic patients as a platelet source. In this approach, we developed a method to produce functional MKs from hiPSC-HSCs using a xeno-free and feeder-free condition and minimize the variation and risk from animal-derived products in cell culture. We have also investigated the genome-wide expression as well as functional significance of long noncoding RNAs (lncRNAs) in hiPSC-HSC-derived MKs to get insight into MK biology. We have performed lncRNAs expression profiling by using the Human LncProfilers qPCR Array Kit and identified 26 differentially regulated lncRNAs in hiPSC-HSC-derived MKs as compared with those in hiPSC-HSCs. HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) was the most highly upregulated lncRNA in hiPSC-HSC-derived MKs and phorbol 12-myristate 13-acetate (PMA)-induced megakaryocytic-differentiating K562 cells. Furthermore, we have studied the potential mechanism of HOTAIRM1 based on the interactions between HOTAIRM1, p53, and miR-125b in PMA-induced K562 cells. Our results demonstrated that during MK maturation, HOTAIRM1 might be associated with the transcriptional regulation of p53 via acting as a decoy for miR-125b. Thus, the interaction between HOTAIRM1, p53, and miR-125b is likely involved in controlling cell cycling (cyclin D1), reactive oxygen species production, and apoptosis to support terminal maturation of MKs. SIGNIFICANCE STATEMENT: In vitro generation of megakaryocytes (MKs) from human-induced pluripotent stem cell-derived hematopoietic stem cells (hiPSC-HSCs) could provide an alternative source of platelets for treating thrombocytopenic patients. This study has investigated the functional significance of long non-coding RNAs in hiPSC-HSC-derived MKs, which remains unclear. This study's findings suggest that the regulatory role of HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) in p53-mediated regulation of cyclin D1 during megakaryocytopoiesis is to promote MK maturation by decoying miR-125b.

Transcriptional profiling of long non-coding RNAs regulating fruit cracking in Punica granatum L. under bagging.

Fruit cracking tremendously damages the appearance of fruit, easily leads to pathogen invasion, greatly reduces the marketability and causes immense economic losses. The pivotal role of long non-coding RNAs (lncRNAs) in diverse biological processes has been confirmed, while the roles of lncRNAs underlying fruit cracking remain poorly understood. In this study, the incidence of fruit cracking was 7.26% under the bagging treatment, the control group was 38.11%, indicating that bagging considerably diminished the fruit cracking rate. LncRNA libraries for fruit cracking (FC), fruit non-cracking (FNC) and fruit non-cracking under bagging (FB) in pomegranate (Punica granatum L.) were performed and analysed via high-throughput transcriptome sequencing. A total of 3194 lncRNAs were obtained with a total length of 4898846 nt and an average length of 1533.77 nt in pomegranate. We identified 42 differentially expressed lncRNAs (DELs) and 137 differentially expressed mRNAs (DEGs) in FC vs FNC and 35 DELs and 160 DEGs in FB vs FC that formed co-expression networks respectively, suggesting that there are involved in phytohormone signaling pathway, lignin catabolic process, lipid transport/binding, cutin biosynthetic process and cell wall organization. We also found that 18 cis-acting DELs regulated 18 target genes, and 10 trans-acting DELs regulated 24 target genes in FC vs FNC, 23 DELs regulate 23 target genes for the cis-acting lncRNAs and 12 DELs regulated 36 target genes in FB vs FC, which provides an understanding for the regulation of the fruit cracking. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results demonstrated that DELs participated in calcium ion binding, glycerophospholipid metabolism, flavonoid biosynthetic process, cell wall biogenesis, xyloglucan metabolic process, hormone signal transduction and starch and sucrose metabolism. Our findings provide new insights into the roles of lncRNAs in regulating the fruit cracking and lay the foundation for further improvement of pomegranate quality.

Lnc-SELPLG-2:1 enhanced osteosarcoma oncogenesis via hsa-miR-10a-5p and the BTRC cascade

BackgroundTo investigate the potential role of Long Non-coding RNAs (lncRNAs) in the progression of osteosarcoma.MethodsThe candidate lncRNAs were screened with RNA-seq and confirmed with quantitative real-time PCR. Using MTS, transwell assay, and flow cytometric analysis, the effects of overexpressed lnc-SELPLG-2:1 on cell functions were determined. Immunohistochemical staining, fluorescence in situ hybridization, and luciferase reporter assay were used to evaluate the potential mechanism of lnc-SELPLG-2:1 in vivo and in vitro using a tumor model. Moreover, the effects of overexpression of hsa-miR-10a-5p on the functions of SaOS2 cells were determined using functional cell analysis. A response test was used to confirm the mechanism by which lnc-SELPLG-2:1 sponge hsa-miR-10a-5p promotes the expression of BTRC to regulate osteosarcoma.ResultsLnc-SELPLG-2:1 was highly expressed in osteosarcoma compared to normal cells and bone and marrow samples. Inhibition of lnc-SELPLG-2:1 accelerated cell apoptosis and suppressed cell proliferation, migration, and invasion, whereas lnc-SELPLG-2:1 overexpression had the opposite effect. Moreover, inhibiting lnc-SELPLG-2:1 in an in vivo model decreased tumor size and suppressed the expression of cell migration-related proteins. The prediction, dual luciferase assay, and response test results indicated that hsa-miR-10-5p and BTRC were involved in the lnc-SELPLG-2:1 cascade. Unlike lnc-SELPLG-2:1, hsa-hsa-miR-10a-5p had opposite expression and function. Competitive binding of lnc-SELPLG-2:1 to hsa-hsa-miR-10a-5p prevented BTRC from miRNA-mediated degradation, thereby activating the expression of VIM, MMP9, and MMP2, promoting osteosarcoma cell proliferation, migration, and invasion, and inhibiting apoptosis.ConclusionLnc-SELPLG-2:1 is an oncogenesis activator in osteosarcoma, and its functions are performed via hsa-miR-10a-5p /BTRC cascade.

Significant Role of Long Non-coding RNAs in Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, with clinical manifestations of resting tremor, akinesia (or bradykinesia), rigidity, and postural instability. However, the molecular pathogenesis of PD is still unclear, and its effective treatments are limited. Substantial evidence demonstrates that long non-coding RNAs (lncRNAs) have important functions in various human diseases, such as cancer, cardiovascular disease, and neurodegenerative diseases. Therefore, the main purpose of this study is to review the role of lncRNAs in the pathogenesis of PD. The role of lncRNAs in the pathogenesis of PD is summarized by reviewing Pubmed. Thirty different lncRNAs are aberrantly expressed in PD and promote or inhibit PD by mediating ubiquitin-proteasome system, autophagy-lysosomal pathway, dopamine (DA) neuronal apoptosis, mitochondrial function, oxidative stress, and neuroinflammation. In this direction, lncRNA may contribute to the treatment of PD as a diagnostic and therapeutic target for PD.

The emerging role of long non-coding RNAs in schizophrenia.

Schizophrenia (SZ) is a severe psychiatric disorder which is contributed by both genetic and environmental factors. However, at present, its specific pathogenesis is still not very clear, and there is a lack of objective and reliable biomarkers. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) are involved in the pathophysiology of several psychiatric disorders, including SZ, and hold promise as potential biomarkers and therapeutic targets for psychiatric disorders. In this review, we summarize and discuss the role of lncRNAs in the pathogenesis of SZ and their potential value as biomarkers and therapeutic targets.

Analysis of the Function of LncRNA-MSTRG.16919.1 in BHV-1-Infected Bovine Kidney Subculture Cells by Transcriptome Sequencing.

Infection of cattle with bovine herpesvirus type 1 (BHV−1) can lead to upper respiratory tract disease, conjunctivitis, or genital disease and cause serious economic losses to the cattle industry worldwide. The role of long noncoding RNAs in BHV−1 infection is not well understood. To explore the role of lncRNA−MSTRG.16919.1 in bovine herpes virus type I (BHV−1) infected MDBK cells, the lncRNA−MSTRG.16919.1 gene was silenced and sequenced transcriptome and sequencing data were analyzed by Edge R software, Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and an interaction network of proteins. Real−time quantitative PCR (RT−qPCR) and Western blotting were used to verify the results of bioinformatic analyses. The results showed that 1151 differential genes were obtained in the siRNA−MSTRG.16919.1 group compared with an NC group. Compared with BHV−33 h, 6586 differentially expressed genes were obtained. A total of 498 differentially expressed genes were screened from the two groups. To verify the accuracy of the sequencing, six genes were randomly selected for RT−qPCR, and the results showed that the expression trend of selected genes was consistent with the sequencing results. GO enrichment analysis showed that the differential genes were related to such biological processes as nucleotide binding, enzyme binding, cell cycle, and glial macromolecule metabolism. KEGG analysis enriched 378 and 2634 signaling pathways, respectively, that were associated with virus infection, ubiquitin−mediated protein hydrolysis, phosphoinositol metabolism, apoptosis, and other metabolic pathways. The STRING protein interaction database was used to analyze the interaction network of proteins encoded by differential genes, and the degree algorithm in Cytoscape was used to screen the top 20 proteins. The results showed that SKIV2L2, JAK2, PIK3CB, and MAPK8 were related to virus infection. Western blot analysis of TNF, NF−κB, MAPK8, MAPK9, and MAPK10 proteins showed that lncRNA−MSTRG.16919.1 was involved in regulating the expression of these functional proteins. The results of this study provide basic information for exploring the function and regulatory mechanism of lncRNA−MSTRG.16919.1 in organisms and help for further studying the interaction between virus and host.

Knockdown of Long Noncoding RNA 01124 Inhibits the Malignant Behaviors of Colon Cancer Cells via miR-654-5p/HAX-1.

Background Previous studies have shown that long noncoding RNAs (lncRNAs) play a key role in cancer, including colon cancer (CC). However, the exact role of long noncoding RNA 01124 (LINC01124) in CC and its mechanisms of action remain unknown. In this study, we investigated the functional effects and the possible mechanism of LINC01124 in CC. Methods We first determined the expression of LINC01124 in CC tissues (The Cancer Genome Atlas (TCGA) database) and cell lines (quantitative real-time polymerase chain reaction (qRT-PCR)). Functional analysis via Cell Counting Kit-8 (CCK-8), colony formation, cell cycle, wound healing and Transwell assays were performed, and a mechanistic experiment was performed with the western blotting. The function of LINC01124 was also determined in vivo using nude BALB/c mice. Results The results showed that LINC01124 was upregulated in CC tissues and cell lines. Functional studies showed that knockdown of LINC01124 significantly suppressed the proliferation, migration, and invasion of colon cancer cells in vitro and in vivo. Subsequent mechanistic experiments indicated that LINC01124 acted as a sponge to suppress microRNA 654-5p, which targeted HAX-1. Downregulation of LINC01124 decreased the expression of HAX-1, and overexpression of the miR-654-5p inhibitor attenuated the sh-LINC01124-induced inhibition of CC cell proliferation, migration, and invasion. Conclusion Collectively, this study revealed that the knockdown of LINC01124 inhibited the malignant behaviors of CC via the miR-654-5p/HAX-1 axis, suggesting that LINC01124 might be a therapeutic target for CC treatment.

LncRNA Miat promotes neuropathic pain through miR-362-3p/BAMBI signaling axis

The treatment of neuropathic pain (NP) has become an important subject to be studied and solved urgently in clinical practice. The role of long noncoding RNAs (lncRNAs) in NP development is becoming clear. Therefore, this study aimed to investigate the role and mechanism of lncRNA Miat in NP. In this study, chronic contractionary injury (CCI) mouse NP model was performed. Firstly, the effects of Miat on pain behavior in mice and the expression levels of pro-inflammatory cytokines and pro-inflammatory proteins in spinal cord tissue were explored by interfering with the expression of Miat. Then, Miat-targeted signaling pathway was predicted by bioinformatics and verified by dual luciferase reporter gene and RNA pull down. Finally, the mechanism of Miat was confirmed by the rescue experiments. Our results demonstrated that Miat knockdown alleviated paw withdrawal threshold, paw withdrawal latency, cold hyperalgesia frequency and neuroinflammation in CCI mice. MiR-362-3p was able to bind to Miat and BAMBI. Overall, Miat upregulated BAMBI by inhibiting miR-362-3p, thereby promoting the occurrence and development of NP. This study analyzed the possibility and effectiveness of targeting Miat for NP clinical treatment, in order to provide new ideas and technical methods for NP gene therapy.

The emerging role of long non-coding RNAs, microRNAs, and an accelerated epigenetic age in Huntington's disease.

Huntington’s disease (HD) is a dominantly inherited neurodegenerative disease with variable clinical manifestations. Recent studies highlighted the contribution of epigenetic alterations to HD progress and onset. The potential crosstalk between different epigenetic layers and players such as aberrant expression of non-coding RNAs and methylation alterations has been found to affect the pathogenesis of HD or mediate the effects of trinucleotide expansion in its pathophysiology. Also, microRNAs have been assessed for their roles in the modulation of HD manifestations, among them are miR-124, miR-128a, hsa-miR-323b-3p, miR-432, miR-146a, miR-19a, miR-27a, miR-101, miR-9*, miR-22, miR-132, and miR-214. Moreover, long non-coding RNAs such as DNM3OS, NEAT1, Meg3, and Abhd11os are suggested to be involved in the pathogenesis of HD. An accelerated DNA methylation age is another epigenetic signature reported recently for HD. The current literature search collected recent findings of dysregulation of miRNAs or lncRNAs as well as methylation changes and epigenetic age in HD.

Enabling factor for cancer hallmark acquisition: Small nucleolar RNA host gene 17.

The role of long non-coding RNA (lncRNA) in human tumors has gradually received increasing attention in recent years. Particularly, the different functions of lncRNAs in different subcellular localizations have been widely investigated. The upregulation of lncRNA small nucleolar RNA host gene 17 (SNHG17) has been observed in various human tumors. Growing evidence has proved that SNHG17 plays a tumor-promoting role in tumorigenesis and development. This paper describes the molecular mechanisms by which SNHG17 contributes to tumor formation and development. The different functions of SNHG17 in various subcellular localizations are also emphasized: its function in the cytoplasm as a competing endogenous RNA (ceRNA), its action in the nucleus as a transcriptional coactivator, and its function through the polycomb repressive complex 2 (PRC2)-dependent epigenetic modifications that regulate transcriptional processes. Finally, the correlation between SNHG17 and human tumors is summarized. Its potential as a novel prognostic and diagnostic biomarker for cancer is explored especially.