Role Of Long Non-coding RNAs Research Articles

Interferon-τ -induced ISG15-AS regulates endometrial receptivity during early goat pregnancy

Endometrial receptivity is a critical process for the successful establishment of pregnancy in ruminants. However, the biological role of long non-coding RNAs (lncRNAs) in the development of endometrial receptivity is poorly understood. In this study, we performed RNA-seq analysis of immortalised goat endometrial epithelial cells (gEECs) treated with interferon-τ (IFNT). Transcriptome profiles showed that 8069 high-confidence putative lncRNAs, including 6498 intronic lncRNA transcripts, 1078 lincRNAs and 493 antisense lncRNAs were identified in gEECs with or without IFNT treatment. Functional clustering analysis was performed by using cis and trans lncRNAs prediction. GO and KEGG analyses revealed that differentially expressed lncRNAs may regulate tissue remodelling and immune responses. Subsequently, six of the 21 differentially expressed antisense lncRNAs were validated using qRT-PCR. Through functional screening and co-expression analysis of lncRNAs in gEECs, we identified that ISG15-AS was mainly expressed in the luminal and glandular epithelium on days 5 and 15 and was strongly upregulated on day 18 of pregnancy in vivo. Similarly, ISG15-AS was abundant in the nucleus and cytoplasm, and was significantly upregulated after treatment with IFNT in gEECs. In addition, ISG15 is an IFNT-responsive gene, that displayed an evident increase in vivo and in vitro. Moreover, sense ISG15 was significantly upregulated following ISG15-AS silencing. The key genes related to ISGylation and endometrial receptivity in gEECs dramatically increased after ISG15-AS inhibition. Collectively, our results indicate that a novel antisense lncRNA, ISG15-AS, may be important in regulating endometrial receptivity through ISGylation.

Coding roles of long non-coding RNAs in breast cancer: Emerging molecular diagnostic biomarkers and potential therapeutic targets with special reference to chemotherapy resistance.

Dysregulation of epigenetic mechanisms have been depicted in several pathological consequence such as cancer. Different modes of epigenetic regulation (DNA methylation (hypomethylation or hypermethylation of promotor), histone modifications, abnormal expression of microRNAs (miRNAs), long non-coding RNAs, and small nucleolar RNAs), are discovered. Particularly, lncRNAs are known to exert pivot roles in different types of cancer including breast cancer. LncRNAs with oncogenic and tumour suppressive potential are reported. Differentially expressed lncRNAs contribute a remarkable role in the development of primary and acquired resistance for radiotherapy, endocrine therapy, immunotherapy, and targeted therapy. A wide range of molecular subtype specific lncRNAs have been assessed in breast cancer research. A number of studies have also shown that lncRNAs may be clinically used as non-invasive diagnostic biomarkers for early detection of breast cancer. Such molecular biomarkers have also been found in cancer stem cells of breast tumours. The objectives of the present review are to summarize the important roles of oncogenic and tumour suppressive lncRNAs for the early diagnosis of breast cancer, metastatic potential, and chemotherapy resistance across the molecular subtypes.

LncRNA WDR11-AS1 Promotes Extracellular Matrix Synthesis in Osteoarthritis by Directly Interacting with RNA-Binding Protein PABPC1 to Stabilize SOX9 Expression.

Osteoarthritis (OA) is a degenerative disease of articular cartilage that is mainly characterized by chronic and mild inflammation of the joints. Recently, many studies have reported the crucial roles of long noncoding RNAs (lncRNAs) in OA as gene transcriptional regulatory factors, diagnostic biomarkers, or therapeutic targets. However, the exact mechanisms of lncRNAs in the regulation of OA progression remain unclear. In the present study, the lncRNA WDR11 divergent transcript (lncRNA WDR11-AS1) was shown to be downregulated in osteoarthritic cartilage tissues from patients, and to promote extracellular matrix (ECM) synthesis in osteoarthritic chondrocytes with knockdown and overexpression experiments. This function of lncRNA WDR11-AS1 was linked to its ability to interact with the polyadenylate-binding protein cytoplasmic 1 (PABPC1), which was screened by RNA pulldown and mass spectrometry analyses. PABPC1 was discovered to bind ECM-related mRNAs such as SOX9, and the inhibition of PABPC1 improved the mRNA stability of SOX9 to mitigate OA progression. Our results suggest that lncRNA WDR11-AS1 has a promising inhibitory effect on inflammation-induced ECM degradation in OA by directly binding PABPC1, thereby establishing lncRNA WDR11-AS1 and PABPC1 as potential therapeutic targets in the treatment of OA.

Explore the role of long noncoding RNAs and mRNAs in intracranial atherosclerotic stenosis: From the perspective of neutrophils.

Circulating neutrophils and long noncoding RNAs (lncRNAs) play various roles in intracranial atherosclerotic stenosis (ICAS). Our study aimed to detect differentially expressed (DE) lncRNAs and mRNAs in circulating neutrophils and explore the pathogenesis of atherosclerosis from the perspective of neutrophils. Nineteen patients with ICAS and 15 healthy controls were enrolled. The peripheral blood of the participants was collected, and neutrophils were separated. The expression profiles of lncRNAs and mRNAs in neutrophils from five patients and five healthy controls were obtained, and DE lncRNAs and mRNAs were selected. Six lncRNAs were selected and validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and ceRNA and lncRNA-RNA binding protein (RBP)-mRNA networks were constructed. Correlation analysis between lncRNAs and mRNAs was performed. Functional enrichment annotations were also performed. Volcano plots and heat maps displayed the expression profiles and DE lncRNAs and mRNAs, respectively. The qRT-PCR results revealed that the four lncRNAs showed a tendency consistent with the expression profile, with statistical significance. The ceRNA network revealed three pairs of regulatory networks: lncRNA RP3-406A7.3-NAGLU, lncRNA HOTAIRM1-MVK/IL-25/GBF1/CNOT4/ANKK1/PLEKHG6, and lncRNA RP11-701H16.4-ZNF416. The lncRNA-RBP-mRNA network showed five pairs of regulatory networks: lncRNA RP11-701H16.4-TEK, lncRNA RP11-701H16.4-MED17, lncRNA SNHG19-NADH-ubiquinone oxidoreductase core subunit V1, lncRNA RP3-406A7.3-Angel1, and lncRNA HOTAIRM1-CARD16. Our study identified and verified four lncRNAs in neutrophils derived from peripheral blood, which may explain the transcriptional alteration of neutrophils during the pathophysiological process of ICAS. Our results provide insights for research related to the pathogenic mechanisms and drug design of ICAS.

Chromatin research and epigenetics - historical perspectives, current research, open questions, and misconceptions

The concept of chromatin as a complex of nucleic acid and proteins in the cell nucleus was developed by cytologists and biochemists in the late 19th century. It was the starting point for biochemical research on DNA and nuclear proteins. Interest in chromatin declined rapidly at the beginning of the 20th century, but a few decades later a new focus on chromatin emerged, which was not only related to its structure, but also to its function in gene regulatory processes in the development of higher organisms. Since the late 20th century, research on chromatin modifications as well as DNA methylation that emerged in the 1970s have also been conducted under the label epigenetics, a term originally introduced for the complex processes between genotype and phenotype during development. These processes - in particular gene regulation - were subsequently scrutinized by molecular biologists. Research termed epigenetics remained marginal until the end of the 20th century but experienced a rapid rise when heritability was added to its definition. This was accompanied by an increasing diversity in researchers' understanding and definitions of epigenetics. Epigenetics now includes research on histone and DNA-modifying enzymes, nucleosome remodelers, histone chaperones, chromatin-binding proteins to facilitate transcription factor and polymerase action, and the role of long non-coding RNA and small interfering RNA in transcriptional regulation. This article highlights the major phases of chromatin and epigenetics research until the present time and illuminates how different scientific contexts changed the relevance and meaning of chromatin from the 19th century. The paper also points to misconceptions and media hype about epigenetics, for example unsupported claims about transgenerational inheritance in humans or questioning of the basic biological principles of gene regulation based on specific regulatory sequences of the genome.

MEG3 alleviates ankylosing spondylitis by suppressing osteogenic differentiation of mesenchymal stem cells through regulating microRNA-125a-5p-mediated TNFAIP3.

Osteoblasts are important regulators of bone formation, but their roles in ankylosing spondylitis (AS) remain unclear. This study aims to explore the role of long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) MEG3 in AS. Serum from AS patients as well as AS mesenchymal stem cells (ASMSCs) and healthy donors mesenchymal stem cells (HDMSCs) was collected. Accordingly, poorly expressed MEG3 and TNF alpha induced protein 3 (TNFAIP3) as well as overexpressed microRNA-125a-5p (miR-125a-5p) were noted in the serum of AS patients and in ASMSCs during the osteogenic induction process. Meanwhile, the interaction among MEG3, miR-125a-5p, and TNFAIP3 was determined and their effect on osteoblast activity was examined in vitro and in vivo. Overexpression of MEG3 and TNFAIP3 or inhibition of miR-125a-5p was found to inactivate the Wnt/β-catenin pathway, thus suppressing osteogenic differentiation of MSCs. MEG3 competitively bound to miR-125a-5p to increase TNFAIP3 expression, thereby inactivating the Wnt/β-catenin pathway and repressing the osteogenic differentiation of MSCs. In proteoglycan (PG)-induced AS mouse models, MEG3 also reduced osteogenic activity of MSCs to inhibit AS progression through the miR-125a-5p/TNFAIP3/Wnt/β-catenin axis. Therefore, up-regulation of MEG3 or depletion of miR-125a-5p holds potential of alleviating AS, which sheds light on a new therapeutic strategy for AS treatment.

LINC02870 facilitates SNAIL translation to promote hepatocellular carcinoma progression.

Exploring the roles of long noncoding RNAs (lncRNAs) in tumorigenesis and metastasis could contribute to the recognition of novel diagnostic and therapeutic targets. LINC02870 is a novel lncRNA, whose role in tumors has not been reported. Herein, we focused on the function and mechanism of LINC02870 in human hepatocellular carcinoma (HCC). We first carried out a pan-cancer study of LINC02870 expression and its relationship to prognosis, and LINC02870 was determined to be a possible oncogene in HCC. Upregulated expressions of LINC02870 were also found in our HCC samples compared to the para-tumor samples. Moreover, overexpression of LINC02870 promoted the growth, migration, and invasion of HCC cells. Subsequently, binding proteins of LINC02870 were identified by a number of in silico analyses, including correlation analysis, signaling network analysis, and survival analysis. Intriguingly, the most promising binding protein of LINC02870 was predicted and confirmed to be eukaryotic translation initiation factor 4 gamma 1 (EIF4G1), an important component of the eukaryotic translation initiation factor 4F complex that initiates cap-dependent translation. Further investigation showed that LINC02870 increased the translation of SNAIL to induce malignant phenotypes in HCC cells. Additionally, HCC patients with higher expression levels of LINC02870 and EIF4G1 had shorter survival times than those with lower expression levels. Thus, our findings suggested that LINC02870 induced SNAIL translation and correlated with poor prognosis and tumor progression in HCC.

The Role of Long Noncoding RNA (lncRNAs) Biomarkers in Renal Cell Carcinoma.

Renal cell carcinoma is one of the common cancers whose incidence and mortality are continuously growing worldwide. Initially, this type of tumour is usually asymptomatic. Due to the lack of reliable diagnostic markers, one-third of ccRCC patients already have distant metastases at the time of diagnosis. This underlines the importance of establishing biomarkers that would enable the prediction of the disease's course and the risk of metastasis. LncRNA, which modulates genes at the epigenetic, transcriptional, and post-transcriptional levels, appears promising. The actions of lncRNA involve sponging and sequestering target miRNAs, thus affecting numerous biological processes. Studies have confirmed the involvement of RNAs in various diseases, including RCC. In this review, we focused on MALAT1 (a marker of serious pathological changes and a factor in the promotion of tumorigenesis), RCAT1 (tumour promoter in RCC), DUXAP9 (a plausible marker of localized ccRCC), TCL6 (exerting tumour-suppressive effects in renal cancer), LINC00342 (acting as an oncogene), AGAP2 Antisense1 (plausible predictor of RCC progression), DLEU2 (factor promoting tumours growth via the regulation of epithelial-mesenchymal transition), NNT-AS1 (sponge of miR-22 contributing to tumour progression), LINC00460 (favouring ccRCC development and progression) and Lnc-LSG1 (a factor that may stimulate ccRCC metastasis).

Long Non-Coding RNA GAS5 Promotes BAX Expression by Competing with microRNA-128-3p in Response to 5-Fluorouracil.

The acquisition of drug resistance is a major hurdle for effective cancer treatment. Although several efforts have been made to overcome drug resistance, the underlying mechanisms have not been fully elucidated. This study investigated the role of long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) in drug resistance. GAS5 was found to be downregulated in colon cancer cell lines that are resistant to 5-fluorouracil (5-FU). Downregulation of GAS5 decreased the viability of HCT116 cells and the level of the pro-apoptotic BAX protein, while GAS5 overexpression promoted cell death in response to 5-FU. The interaction between GAS5 and BAX mRNA was investigated using MS2-tagged RNA affinity purification (MS2-trap) followed by RT-qPCR, and the results showed that GAS5 bound to the 3'-untranslated region of BAX mRNA and enhanced its expression by interfering with the inhibitory effect of microRNA-128-3p, a negative regulator of BAX. In addition, ectopic expression of GAS5 increased the sensitivity of resistant cells in response to anti-cancer drugs. These results suggest that GAS5 promoted cell death by interfering with miR-128-3p-mediated BAX downregulation. Therefore, GAS5 overexpression in chemo-resistant cancer cells may be a potential strategy to improve the anti-cancer efficacy of drugs.

Genome-wide identification and comprehensive analysis reveal potential roles of long non-coding RNAs in fruit development of southern highbush blueberry (Vaccinium corymbosum L.).

Blueberries have a high antioxidant content and are produced as healthy food worldwide. Long non-coding RNAs (lncRNAs) are a type of regulatory RNAs that play a variety of roles in plants. Nonetheless, information on lncRNAs and their functions during blueberry fruit development is scarce in public databases. In the present study, we performed genome-wide identification of lncRNAs in a southern highbush blueberry using strand-specific RNA sequencing (ssRNA-Seq). Differentially expressed lncRNAs (DE-lncRNAs) and their potential target genes were analyzed at four stages of fruit development. Cis-regulatory DE-lncRNAs were predicted using co-localization analysis. These findings included a total of 25,036 lncRNAs from 17,801 loci. Blueberry lncRNAs had shorter transcript lengths, smaller open reading frame (ORF) sizes, fewer exons, and fewer isoforms than protein-coding RNAs, as well as lower expression levels and higher stage-specificity during fruit development. A total of 105 DE-lncRNAs were identified among the comparison group of PAD vs. CUP, 443 DE-lncRNAs were detected when comparing CUP with PINK fruits, and 285 DE-lncRNAs were revealed when comparing PINK and BLUE fruits. According to Kyoto Encyclopedia of Genes and Genomes annotation, target genes of DE-lncRNAs were primarily enriched in the "Autophagy-other", "DNA replication", "Endocytosis", 'photosynthesis' and 'chlorophyll metabolism' pathways, suggesting that lncRNAs may pay potential roles in fruit expansion and ripening. Moreover, several lncRNAs have been proposed as cis-regulators of the key genes involved in flavonoid biosynthesis. MSTRG.107242.6, and its putative target gene, BTB/POZ and TAZ domain-containing protein, might play critical roles in anthocyanin accumulation in blueberries. These findings highlight the regulatory function of lncRNAs and aid in elucidating the molecular mechanism underlying blueberry fruit growth.

Роль длинных некодирующих РНК и ДНК-метилирования в патогенезе рака яичников

Рак яичников (РЯ) представляет собой группу агрессивных гетерогенных злокачественных опухолей, характеризующихся быстрой прогрессией, низким диагностическим потенциалом, высокой частотой неблагоприятных исходов и высоким потенциалом метастазирования. В обзоре авторы концентрируют внимание на одном из основных регуляторов клеточных процессов, приводящем к образованию опухолей, а именно на длинных некодирующих РНК (днРНК). Известно, что они участвуют в регуляции экспрессии генов на транскрипционном, пост-транскрипционном, трансляционном и пост-трансляционном уровнях, оказывая влияние на такие фундаментальные биологические процессы, как дифференцировка, пролиферация, дозовая компенсация генов, ремоделирование хроматина, геномный импринтинг, альтернативный сплайсинг прем РНК и другие. Они могут выступать как в роли онкогенов, так и в роли генов-супрессоров опухолей. Многочисленные данные показывают, что днРНК вовлечены в патогенез рака яичников, а их аберрантное метилирование представляет один из эпигенетических механизмов регуляции их собственной экспрессии. цель обзора изучение вклада днРНК и ДНК-метилирования в процессы онкогенеза рака яичников и их потенциала в качестве биомаркеров. Особое внимание уделено применению экзосомальных днРНК в неинвазивной диагностике рака яичников.методика. Проведен анализ литературы по международным базам Scopus, Web of science по ключевым словам: рак яичников, длинные некодирующие РНК, ДНК-метилирование. В соответствии с целью обзора предложены и утверждены части, раскрывающие потенциал нкРНК в патогенезе РЯ. Заключение. Изучение свойств днРНК и ДНК-метилирования - путь к улучшению прогноза заболевания, общей выживаемости и качества жизни пациенток с РЯ, к появлению принципиально новых биомаркеров для ранней диагностики, разработки таргетной терапии и персонализированному лечению этого социально значимого заболевания. Background. Ovarian cancer (OC) is a group of aggressive heterogeneous malignant neoplasms characterized by rapid progression, low diagnostic potential, high incidence of adverse outcomes, and high potential for metastasis. The present review focuses on one of the main regulators of cell processes that lead to the formation of tumors, namely, long non-coding RNAs (lncRNAs). It is known that they are involved in the regulation of gene expression at the transcriptional, post-transcriptional, translational, and post-translational levels, thereby influencing fundamental biological processes, such as differentiation, proliferation, dose compensation of genes, chromatin remodeling, genomic imprinting, alternative pre-mRNA splicing, and others. lncRNAs can act both as oncogenes and as tumor suppressor genes. Multiple reports show that lncRNAs are involved in the pathogenesis of OC, and their aberrant methylation is one of the most important epigenetic mechanisms for regulation of their own expression.the aim of this review is to address the contribution of IncRNAs and DNA methylation to the oncogenesis of OC and the lncRNA potential as biomarkers. Special attention is paid to the use of exosomal lncRNAs in non-invasive diagnostics of OC.methods. The search for literature was performed in the Scopus and Web of Science databases using the following keywords: ovarian cancer, long non-coding RNAs, DNA methylation. In accordance with the objectives of the review, the parts that addressed the role of IncRNAs in the pathogenesis of OC were proposed and approved. All articles used in the review were obtained from open sources.conclusion. Studying IncRNA properties and DNA methylation will improve the prognosis, overall survival, and quality of life of patients with OC. Such studies will help developing fundamentally new biomarkers, targeted therapy and personalized treatment of this socially significant disease.

Long noncoding RNA WT1-AS regulates trophoblast proliferation, migration, and invasion via the microRNA-186-5p/CADM2 axis.

This study aimed to determine the role of long noncoding RNA (lncRNA) WT1 antisense RNA (WT1-AS) in the occurrence and progression of preeclampsia (PE) and to determine the underlying molecular mechanisms. The associations between WT1-AS and microRNA (miR)-186-5p, and miR-186-5p and cell adhesion molecule 2 (CADM2) were predicted using StarBase software and verified via dual-luciferase assays. To explore the role of the human chorionic trophoblast line HTR-8/SVneo, gene (WT1-AS/miR-186-5p) gain/loss of function experiments were performed. Qualitative reverse transcription-polymerase chain reaction (RT-PCR) analysis was used to evaluate transfection efficiency. Cell proliferation, apoptosis, cell migration, and invasion were assessed using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry, and transwell analysis, respectively. Moreover, CADM2 protein expression was measured by western blotting. The results indicated that overexpression of WT1-AS inhibited cell viability, migration, and invasion, and induced apoptosis in HTR-8/SVneo cells. We observed that miR-186a-5p directly targeted WT1-AS, and miR-186a-5p knockdown reversed the effects of WT1-AS knockdown in HTR-8/SVneo cells. Binding sites were found between miR-186-5p and CADM2, and CADM2-overexpression reversed the influence of miR-186-5p mimic on HTR-8/SVneo cells. In summary, our findings demonstrated that lncRNA WT1-AS participates in PE by regulating the proliferation and invasion of placental trophoblasts, through the miR-186-5p/CADM2 axis.

Long noncoding RNA UCA1 promotes the expression and function of P-glycoprotein by sponging miR-16-5p in human placental BeWo cells.

Investigations on placental P-glycoprotein (P-gp) regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. The role of long noncoding RNA (lncRNA) on placental P-gp regulation is lacking. The present study was carried out to investigate the regulation and underlying mechanisms of lncRNA urothelial carcinoma associated 1 (UCA1) on P-gp in Bewo cells. lncRNA UCA1 inhibition or overexpression could decrease or increase ABCB1 mRNA expression, P-gp expression and its cellular efflux function, respectively. RNA-FISH revealed that lncRNA UCA1 was mainly located in the cytoplasm of Bewo cells. MicroRNA array was applied and 10 significant miRNAs was identified after lncRNA UCA1 inhibition. Databases of LncTarD, LncRNA2Target, and miRcode were further used to search potential target miRNAs of lncRNA UCA1 and miR-16-5p was screened out. Thereafter, we confirmed that miR-16-5p expression was significantly upregulated or reduced after lncRNA UCA1 knockdown or overexpression, respectively. Furthermore, we also proved that ABCB1 mRNA expression, P-gp expression and its cellular efflux function was enhanced or reduced after miR-16-5p inhibition or overexpression, respectively. The rescue experiment further indicated that miR-16-5p was involved in the positive regulation of lncRNA UCA1 on the expression and function of P-gp. Lastly, dual-luciferase reporter system, RNA-binding protein immunoprecipitation and RNA pull-down assays were performed to explore the relationships among lncRNA UCA1, miR-16-5p, and ABCB1. It was found that lncRNA UCA1(1103-1125) could directly interact with miR-16-5p and miR-16-5p could directly target ABCB1 coding DNA sequence region (882-907). In conclusion, LncRNA UCA1 could promote the expression and function of P-gp by sponging miR-16-5p in BeWo cells.

Insights into the role of long non-coding RNAs in DNA methylation mediated transcriptional regulation.

DNA methylation is one of the most important epigenetic mechanisms that governing regulation of gene expression, aberrant DNA methylation patterns are strongly associated with human malignancies. Long non-coding RNAs (lncRNAs) have being discovered as a significant regulator on gene expression at the epigenetic level. Emerging evidences have indicated the intricate regulatory effects between lncRNAs and DNA methylation. On one hand, transcription of lncRNAs are controlled by the promoter methylation, which is similar to protein coding genes, on the other hand, lncRNA could interact with enzymes involved in DNA methylation to affect the methylation pattern of downstream genes, thus regulating their expression. In addition, circular RNAs (circRNAs) being an important class of noncoding RNA are also found to participate in this complex regulatory network. In this review, we summarize recent research progress on this crosstalk between lncRNA, circRNA, and DNA methylation as well as their potential functions in complex diseases including cancer. This work reveals a hidden layer for gene transcriptional regulation and enhances our understanding for epigenetics regarding detailed mechanisms on lncRNA regulatory function in human cancers.

Unveiling the Vital Role of Long Non-Coding RNAs in Cardiac Oxidative Stress, Cell Death, and Fibrosis in Diabetic Cardiomyopathy.

Diabetes mellitus is a burdensome public health problem. Diabetic cardiomyopathy (DCM) is a major cause of mortality and morbidity in diabetes patients. The pathogenesis of DCM is multifactorial and involves metabolic abnormalities, the accumulation of advanced glycation end products, myocardial cell death, oxidative stress, inflammation, microangiopathy, and cardiac fibrosis. Evidence suggests that various types of cardiomyocyte death act simultaneously as terminal pathways in DCM. Long non-coding RNAs (lncRNAs) are a class of RNA transcripts with lengths greater than 200 nucleotides and no apparent coding potential. Emerging studies have shown the critical role of lncRNAs in the pathogenesis of DCM, along with the development of molecular biology technologies. Therefore, we summarize specific lncRNAs that mainly regulate multiple modes of cardiomyopathy death, oxidative stress, and cardiac fibrosis and provide valuable insights into diagnostic and therapeutic biomarkers and strategies for DCM.

Regulation of Tumor Metabolome by Long Non-Coding RNAs

Tumorigenesis necessitates enhanced ability for macromolecular biosynthesis, higher energy/ATP levels and co-ordinated redox balance systems within the cancer cells as well as the cellular components of the tumor microenvironment. Cancer cells have adapted several mechanisms to accommodate their growing need for energy and macromolecular building blocks. A critical mechanism that sustains cancer growth and progression is metabolic reprogramming. Metabolic reprogramming refers to the process that changes the pattern of metabolism in these cells that regulates cancer energetics and metabolic biosynthesis. Recent studies have shown a role for long non-coding RNAs (lncRNAs) in the metabolic reprogramming of multiple cell types in cancer tissue. LncRNAs play a decisive role in the reprogramming of glucose, lipid, amino acid, and nucleotide metabolisms to promote tumor growth. Emerging tumorigenic role of lncRNAs and the diverse mechanisms through which they reprogram tumor metabolome is comprehensively discussed here.

Long non-coding RNA NCK1-AS1 functions as a ceRNA to regulate cell viability and invasion in esophageal squamous cell carcinoma via microRNA-133b/ENPEP axis

ABSTRACT This study is designed to explore the role of long non-coding RNAs (lncRNAs) NCK1-AS1 in proliferative and invasive activities of esophageal squamous cell carcinoma (ESCC) cells by binding to microRNA-133b (miR-133b) to regulate ENPEP. Differentially expressed lncRNAs, miRs, genes and their targeting relationships were screened on ESCC-related gene expression datasets GSE17351 and GSE6188. The targeting relationships among NCK1-AS1, miR-133b, and ENPEP were verified using functional assays. Loss- and gain- of function assays were carried out to examine the roles of NCK1-AS1, miR-133b, and ENPEP in ESCC cell proliferative, invasive, migrative and apoptotic abilities as well as tumorigenesis in vivo. Elevated NCK1-AS1 and ENPEP but reduced miR-133b expression were found in ESCC. NCK1-AS1 knockdown or miR-133b overexpression inhibited the malignant properties of ESCC cells as well as tumorigenesis in vivo. NCK1-AS1 regulated the ENPEP expression by competitively binding to miR-133b. ENPEP overexpression reversed inhibition of NCK1-AS1 knockdown on the function of ESCC cells. This study provides evidence that silencing NCK1-AS1 inhibits expression of ENPEP by sponging miR-133b, thereby suppressing ESCC.

Role of Long Noncoding RNAs in the Regulation of Cellular Immune Response and Inflammatory Diseases.

Long noncoding RNAs (lncRNAs) are recently discovered genetic regulatory molecules that regulate immune responses and are closely associated with the occurrence and development of various diseases, including inflammation, in humans and animals. Under specific physiological conditions, lncRNA expression varies at the cell or tissue level, and lncRNAs can bind to specific miRNAs, target mRNAs, and target proteins to participate in certain processes, such as cell differentiation and inflammatory responses, via the corresponding signaling pathways. This review article summarizes the regulatory role of lncRNAs in macrophage polarization, dendritic cell differentiation, T cell differentiation, and endothelial and epithelial inflammation. In addition, it describes the molecular mechanism of lncRNAs in acute kidney injury, hepatitis, inflammatory injury of the lung, osteoarthritis, mastitis, and neuroinflammation to provide a reference for the molecular regulatory network as well as the genetic diagnosis and treatment of inflammatory diseases in humans and animals.

Role of long non-coding RNAs in rice reproductive development.

Rice is a staple crop, feeding over half of the global population. The future demand of population growth and climate change requires substantial rice improvement. Recent advances in rice genomics have highlighted the vital role of the non-coding part of the genome. The protein-coding regions account for only a tiny portion of the eukaryotic genome, and most of the genomic regions transcribe copious amounts of non-coding RNAs. Of these, the long non-coding RNAs, including linear non-coding RNAs (lncRNAs) and circular non-coding RNAs (circRNAs), have been shown to play critical roles in various developmental processes by regulating the expression of genes and functions of proteins at transcriptional, post-transcriptional and post-translational levels. With the advances in next-generation sequencing technologies, a substantial number of long non-coding RNAs have been found to be expressed in plant reproductive organs in a cell- and tissue-specific manner suggesting their reproductive development-related functions. Accumulating evidence points towards the critical role of these non-coding RNAs in flowering, anther, and pollen development, ovule and seed development and photoperiod and temperature regulation of male fertility. In this mini review, we provide a brief overview of the role of the linear and circular long non-coding RNAs in rice reproductive development and control of fertility and crop yield.

Potential role of long noncoding RNA RP5-881L22.5 as a novel biomarker and therapeutic target of colorectal cancer.

The incidence of colorectal cancer in humans is high, and it is in the top five for cancer-related morbidity and mortality. It is one of the main threats to human health. The function of long noncoding RNAs in tumor occurrence and development has gradually gained attention in recent years. In increasing numbers of studies, researchers have demonstrated that it plays an important role in the pathogenesis of colorectal cancer. To find out if long noncoding RNA RP5-881L22.5 played a role in the pathogenesis of colorectal cancer in relation to the tumor microenvironment. We analyzed the transcriptome data and clinical data in The Cancer Genome Atlas-colon adenocarcinoma. The CIRBERSORT algorithm was applied to evaluate these tumor-infiltrating immune cells in The Cancer Genome Atlas-colon adenocarcinoma cancer tissue samples. Using the "estimate" package in R, we assessed the tumor immune microenvironment. The expression level of RP5-881L22.5 in tumor tissue and adjacent normal tissue samples from 4 pairs of colorectal cancer patients was determined by quantitative reverse transcription PCR. Colorectal cancer cells were tested for invasiveness using a transwell invasion assay after RP5-881L22.5 expression was knocked down. The expression of lncRNA RP5-881L22.5 was related to the clinical characteristics of the tumors, and it was negatively related to the infiltration level of immune cells in the tumor microenvironment and the expression of T cell inhibitory receptors. A major function of its coexpressed mRNA was to regulate tumor immunity, such as the immune response. When quantitative reverse transcription PCR was performed on tumor tissues from 4 pairs of colorectal cancer patients, the results showed that RP5-881L22.5 was highly expressed. Subsequently, knocking down the expression of RP5-881L22.5, the invasiveness of colorectal cancer cell lines was reduced, and the apoptosis rate was increased. RP5-881L22.5 plays a crucial role in the microenvironment of tumors as well as in the pathogenesis of colorectal cancer. The relationship between RP5-881L22.5 and the tumor immune microenvironment deserves further study.