Mapping and Quantification of Non-Coding RNA Originating from the rDNA in Human Glioma Cells

Ribosomal DNA is one of the most conserved parts of the genome, especially in its rRNA coding regions, but some puzzling pieces of its noncoding repetitive sequences harbor secrets of cell growth and development machinery. Disruptions in the neat mechanisms of rDNA orchestrating the cell functioning result in malignant conversion. In cancer cells, the organization of rRNA coding genes and their transcription somehow differ from that of normal cells, but little is known about the particular mechanism for this switch. In this study, we demonstrate that the region ~2 kb upstream of the rDNA promoter is transcriptionally active in one type of the most malignant human brain tumors, and we compare its expression rate to that of healthy human tissues and cell cultures. Sense and antisense non-coding RNA transcripts were detected and mapped, but their secondary structure and functions remain to be elucidated. We propose that the transcripts may relate to a new class of so-called promoter-associated RNAs (pRNAs), or have some other regulatory functions. We also hope that the expression of these non-coding RNAs can be used as a marker in glioma diagnostics and prognosis.

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Human Endometrial Carcinogenesis Is Associated with Significant Reduction in Long Non-Coding RNA, TERRA

International Journal of Molecular Sciences ◽

10.3390/ijms21228686 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8686

Author(s):

Meera Adishesh ◽

Rafah Alnafakh ◽

Duncan M. Baird ◽

Rhiannon E. Jones ◽

Shannon Simon ◽

...

Keyword(s):

Cellular Proliferation ◽

Telomerase Activity ◽

Human Endometrium ◽

Future Research ◽

Healthy Human ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Length Analysis ◽

Regulatory Functions ◽

Long Non Coding Rna

Telomeres are transcribed as long non-coding RNAs called TERRAs (Telomeric repeat containing RNA) that participate in a variety of cellular regulatory functions. High telomerase activity (TA) is associated with endometrial cancer (EC). This study aimed to examine the levels of three TERRAs, transcribed at chromosomes 1q-2q-4q-10q-13q-22q, 16p and 20q in healthy (n = 23) and pathological (n = 24) human endometrium and to examine their association with cellular proliferation, TA and telomere lengths. EC samples demonstrated significantly reduced levels of TERRAs for Chromosome 16p (Ch-16p) (p < 0.002) and Chromosome 20q (Ch-20q) (p = 0.0006), when compared with the postmenopausal samples. No significant correlation was found between TERRA levels and TA but both Ch-16p and Ch-20q TERRA levels negatively correlated with the proliferative marker Ki67 (r = −0.35, p = 0.03 and r = −0.42, p = 0.01 respectively). Evaluation of single telomere length analysis (STELA) at XpYp telomeres demonstrated a significant shortening in EC samples when compared with healthy tissues (p = 0.002). We detected TERRAs in healthy human endometrium and observed altered individual TERRA-specific levels in malignant endometrium. The negative correlation of TERRAs with cellular proliferation along with their significant reduction in EC may suggest a role for TERRAs in carcinogenesis and thus future research should explore TERRAs as potential therapeutic targets in EC.

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Transcriptomic and ChIP-seq Integrative Analysis Reveals Important Roles of Epigenetically Regulated lncRNAs in Placental Development in Meishan Pigs

Genes ◽

10.3390/genes11040397 ◽

2020 ◽

Vol 11 (4) ◽

pp. 397

Author(s):

Dadong Deng ◽

Xihong Tan ◽

Kun Han ◽

Ruimin Ren ◽

Jianhua Cao ◽

...

Keyword(s):

Differentially Expressed ◽

Rna Seq ◽

Sequencing Data ◽

Placental Development ◽

Cytoskeleton Organization ◽

New Class ◽

Chromatin Immunoprecipitation Sequencing ◽

Non Coding Rnas ◽

Two Stages ◽

Regulatory Functions

The development of the placental fold, which increases the maternal–fetal interacting surface area, is of primary importance for the growth of the fetus throughout the whole pregnancy. However, the mechanisms involved remain to be fully elucidated. Increasing evidence has revealed that long non-coding RNAs (lncRNAs) are a new class of RNAs with regulatory functions and could be epigenetically regulated by histone modifications. In this study, 141 lncRNAs (including 73 up-regulated and 68 down-regulated lncRNAs) were identified to be differentially expressed in the placentas of pigs during the establishment and expanding stages of placental fold development. The differentially expressed lncRNAs and genes (DElncRNA-DEgene) co-expression network analysis revealed that these differentially expressed lncRNAs (DElncRNAs) were mainly enriched in pathways of cell adhesion, cytoskeleton organization, epithelial cell differentiation and angiogenesis, indicating that the DElncRNAs are related to the major events that occur during placental fold development. In addition, we integrated the RNA-seq (RNA sequencing) data with the ChIP-seq (chromatin immunoprecipitation sequencing) data of H3K4me3/H3K27ac produced from the placental samples of pigs from the two stages (gestational days 50 and 95). The analysis revealed that the changes in H3K4me3 and/or H3K27ac levels were significantly associated with the changes in the expression levels of 37 DElncRNAs. Furthermore, several H3K4me3/H3K27ac-lncRNAs were characterized to be significantly correlated with genes functionally related to placental development. Thus, this study provides new insights into understanding the mechanisms for the placental development of pigs.

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The role of non-coding RNA/microRNAs in cardiac disease

10.1093/med/9780198757269.003.0031 ◽

2018 ◽

Author(s):

Yolan J. Reckman ◽

Yigal M. Pinto

Keyword(s):

Myocardial Infarction ◽

Cardiac Hypertrophy ◽

Cardiac Disease ◽

Cardiac Development ◽

Rna Transcripts ◽

The Past ◽

Non Coding Rna ◽

Organ Systems ◽

Non Coding Rnas

In the past two decades, our knowledge about non-coding DNA has increased tremendously. While non-coding DNA was initially discarded as ‘junk DNA’, we are now aware of the important and often crucial roles of RNA transcripts that do not translate into protein. Non-coding RNAs (ncRNAs) play important functions in normal cellular homeostasis and also in many diseases across all organ systems. Among the different ncRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been studied the most. In this chapter we discuss the role of miRNAs and lncRNAs in cardiac disease. We present examples of miRNAs with fundamental roles in cardiac development (miR-1), hypertrophy (myomiRs, miR-199, miR-1/133), fibrosis (miR-29, miR-21), myocardial infarction (miR-15, miR17~92), and arrhythmias/conduction (miR-1). We provide examples of lncRNAs related to cardiac hypertrophy (MHRT, CHRF), myocardial infarction (ANRIL, MIAT), and arrhythmias (KCNQ1OT1). We also discuss miRNAs and lncRNAs as potential therapeutic targets or biomarkers in cardiac disease.

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The Emerging Role of Long Non-Coding RNAs in Plant Defense Against Fungal Stress

International Journal of Molecular Sciences ◽

10.3390/ijms21082659 ◽

2020 ◽

Vol 21 (8) ◽

pp. 2659

Author(s):

Hong Zhang ◽

Huan Guo ◽

Weiguo Hu ◽

Wanquan Ji

Keyword(s):

Stress Responses ◽

Higher Plants ◽

Regulatory Elements ◽

Cellular Functions ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Resistance To Infection ◽

Regulatory Functions ◽

Long Non Coding Rna

Growing interest and recent evidence have identified long non-coding RNA (lncRNA) as the potential regulatory elements for eukaryotes. LncRNAs can activate various transcriptional and post-transcriptional events that impact cellular functions though multiple regulatory functions. Recently, a large number of lncRNAs have also been identified in higher plants, and an understanding of their functional role in plant resistance to infection is just emerging. Here, we focus on their identification in crop plant, and discuss their potential regulatory functions and lncRNA-miRNA-mRNA network in plant pathogen stress responses, referring to possible examples in a model plant. The knowledge gained from a deeper understanding of this colossal special group of plant lncRNAs will help in the biotechnological improvement of crops.

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Evolutionary Patterns of Non-Coding RNA in Cardiovascular Biology

Non-Coding RNA ◽

10.3390/ncrna5010015 ◽

2019 ◽

Vol 5 (1) ◽

pp. 15 ◽

Cited By ~ 5

Author(s):

Shrey Gandhi ◽

Frank Ruehle ◽

Monika Stoll

Keyword(s):

Vascular System ◽

Functional Characterization ◽

Evolutionary Patterns ◽

Protein Coding ◽

Rna Transcripts ◽

Non Coding Rna ◽

High Prevalence ◽

Cardiovascular Biology ◽

Non Coding Rnas

Cardiovascular diseases (CVDs) affect the heart and the vascular system with a high prevalence and place a huge burden on society as well as the healthcare system. These complex diseases are often the result of multiple genetic and environmental risk factors and pose a great challenge to understanding their etiology and consequences. With the advent of next generation sequencing, many non-coding RNA transcripts, especially long non-coding RNAs (lncRNAs), have been linked to the pathogenesis of CVD. Despite increasing evidence, the proper functional characterization of most of these molecules is still lacking. The exploration of conservation of sequences across related species has been used to functionally annotate protein coding genes. In contrast, the rapid evolutionary turnover and weak sequence conservation of lncRNAs make it difficult to characterize functional homologs for these sequences. Recent studies have tried to explore other dimensions of interspecies conservation to elucidate the functional role of these novel transcripts. In this review, we summarize various methodologies adopted to explore the evolutionary conservation of cardiovascular non-coding RNAs at sequence, secondary structure, syntenic, and expression level.

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Long Non-Coding RNA in the Pathogenesis of Cancers

Cells ◽

10.3390/cells8091015 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1015 ◽

Cited By ~ 72

Author(s):

Chi ◽

Wang ◽

Yu ◽

Yang

Keyword(s):

Early Stage ◽

Gene Expressions ◽

Rna Transcripts ◽

The Past ◽

Non Coding Rna ◽

Incidence And Mortality ◽

Non Coding Rnas ◽

Tumor Growth And Metastasis ◽

New Biomarkers ◽

Long Non Coding Rna

The incidence and mortality rate of cancer has been quickly increasing in the past decades. At present, cancer has become the leading cause of death worldwide. Most of the cancers cannot be effectively diagnosed at the early stage. Although there are multiple therapeutic treatments, including surgery, radiotherapy, chemotherapy, and targeted drugs, their effectiveness is still limited. The overall survival rate of malignant cancers is still low. It is necessary to further study the mechanisms for malignant cancers, and explore new biomarkers and targets that are more sensitive and effective for early diagnosis, treatment, and prognosis of cancers than traditional biomarkers and methods. Long non-coding RNAs (lncRNAs) are a class of RNA transcripts with a length greater than 200 nucleotides. Generally, lncRNAs are not capable of encoding proteins or peptides. LncRNAs exert diverse biological functions by regulating gene expressions and functions at transcriptional, translational, and post-translational levels. In the past decade, it has been demonstrated that the dysregulated lncRNA profile is widely involved in the pathogenesis of many diseases, including cancer, metabolic disorders, and cardiovascular diseases. In particular, lncRNAs have been revealed to play an important role in tumor growth and metastasis. Many lncRNAs have been shown to be potential biomarkers and targets for the diagnosis and treatment of cancers. This review aims to briefly discuss the latest findings regarding the roles and mechanisms of some important lncRNAs in the pathogenesis of certain malignant cancers, including lung, breast, liver, and colorectal cancers, as well as hematological malignancies and neuroblastoma.

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Non-coding RNA-Encoded Peptides/Proteins in Human Cancer: The Future for Cancer Therapy

Current Medicinal Chemistry ◽

10.2174/0929867328666211111163701 ◽

2021 ◽

Vol 28 ◽

Author(s):

Seyedeh Zahra Bakhti ◽

Saeid Latifi-Navid

Keyword(s):

Cancer Metabolism ◽

Human Cancer ◽

Open Reading Frames ◽

Clinical Value ◽

Rna Transcripts ◽

Non Coding Rna ◽

Present Information ◽

Regulatory Functions ◽

Potential Use

: Although non-coding RNAs (ncRNAs) were initially thought to be a class of RNA transcripts with no encoding capability, it has been established that some ncRNAs actually contain open reading frames (ORFs), which can be translated into micropeptides or microproteins. Recent studies have reported that ncRNAs-derived micropeptides/microproteins have regulatory functions on various biological and oncological processes. Some of these micropeptides/microproteins act as tumor inhibitors and some as tumor inducers. Understanding the carcinogenic role of ncRNAs-encoded micropeptides/microproteins seems to pose potential challenges to cancer research and offer promising practical perspectives on cancer treatment. In this review, we summarized the present information on the association of ncRNAs-derived micropeptides/microproteins with different types of human cancers. We also mentioned their carcinogenic mechanisms in cancer metabolism, signaling pathways, cell proliferation, angiogenesis, metastasis, and so on. Finally, we discussed the potential clinical value of these micropeptides/microproteins and their potential use in the diagnosis and treatment of cancer. This information may help discover, optimize, and develop new tools based on biological micropeptides/microproteins for the early diagnosis and development of anticancer drugs.

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Reducing the structure bias of RNA-Seq reveals a large number of non-annotated non-coding RNA

Nucleic Acids Research ◽

10.1093/nar/gkaa028 ◽

2020 ◽

Vol 48 (5) ◽

pp. 2271-2286 ◽

Cited By ~ 7

Author(s):

Vincent Boivin ◽

Gaspard Reulet ◽

Olivier Boisvert ◽

Sonia Couture ◽

Sherif Abou Elela ◽

...

Keyword(s):

Gene Annotation ◽

Gene Prediction ◽

Structural Features ◽

Genomic Research ◽

Interacting Proteins ◽

Rna Seq ◽

Rna Transcripts ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Rna Genes

Abstract The study of RNA expression is the fastest growing area of genomic research. However, despite the dramatic increase in the number of sequenced transcriptomes, we still do not have accurate estimates of the number and expression levels of non-coding RNA genes. Non-coding transcripts are often overlooked due to incomplete genome annotation. In this study, we use annotation-independent detection of RNA reads generated using a reverse transcriptase with low structure bias to identify non-coding RNA. Transcripts between 20 and 500 nucleotides were filtered and crosschecked with non-coding RNA annotations revealing 111 non-annotated non-coding RNAs expressed in different cell lines and tissues. Inspecting the sequence and structural features of these transcripts indicated that 60% of these transcripts correspond to new snoRNA and tRNA-like genes. The identified genes exhibited features of their respective families in terms of structure, expression, conservation and response to depletion of interacting proteins. Together, our data reveal a new group of RNA that are difficult to detect using standard gene prediction and RNA sequencing techniques, suggesting that reliance on actual gene annotation and sequencing techniques distorts the perceived architecture of the human transcriptome.

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Genome-wide analysis of long non-coding RNA expression and function in colorectal cancer

Tumor Biology ◽

10.1177/1010428317703650 ◽

2017 ◽

Vol 39 (5) ◽

pp. 101042831770365 ◽

Cited By ~ 10

Author(s):

Fangyuan Jing ◽

Huicheng Jin ◽

Yingying Mao ◽

Yingjun Li ◽

Ye Ding ◽

...

Keyword(s):

Colorectal Cancer ◽

Expression Profile ◽

Colorectal Carcinogenesis ◽

Rna Expression ◽

Rna Transcripts ◽

Non Coding Rna ◽

Tumor Tissues ◽

Non Coding Rnas ◽

Long Non Coding Rna

Long non-coding RNAs (lncRNAs) are widely transcribed in the genome, but their expression profile and roles in colorectal cancer are not well understood. The aim of this study was to investigate the long non-coding RNA expression profile in colorectal cancer and look for potential diagnostic biomarkers of colorectal cancer. Long non-coding RNA microarray was applied to investigate the global long non-coding RNA expression profile in colorectal cancer. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed using standard enrichment computational methods. The expression levels of selected long non-coding RNAs were validated by quantitative reverse transcription polymerase chain reaction. The relationship between long non-coding RNA expression levels and clinicopathological characteristics of colorectal cancer patients was assessed. Coexpression analyses were carried out to find the coexpressed genes of differentially expressed long non-coding RNAs, followed by gene ontology analysis to predict the possible role of the selected long non-coding RNAs in colorectal carcinogenesis. In this study, a total of 1596 long non-coding RNA transcripts and 1866 messenger RNA transcripts were dysregulated in tumor tissues compared with paired normal tissues. The top upregulated long non-coding RNAs in tumor tissues were CCAT1, UCA1, RP5-881L22.5, NOS2P3, and BC005081 and the top downregulated long non-coding RNAs were AK055386, AC078941.1, RP4-800J21.3, RP11-628E19.3, and RP11-384P7.7. Long non-coding RNA UCA1 was significantly upregulated in colon cancer, and AK055386 was significantly downregulated in tumor with dimension <5 cm. Functional prediction analyses showed that both the long non-coding RNAs coexpress with cell cycle related messenger RNAs. The current long non-coding RNA study provided novel insights into expression profile in colorectal cancer and predicted the potential roles of long non-coding RNAs in colorectal carcinogenesis. Among the dysregulated long non-coding RNAs, UCA1 was found to be associated with anatomic site, and AK055386 was found associated with tumor size. Further functional investigations into the molecular mechanisms are warranted to clarify the role of long non-coding RNA in colorectal carcinogenesis.

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Η συμβολή των μεγάλων μη-κωδικών (long non-coding) RNAs στην αιτιοπαθογένεια των ΙΦΝΕ

10.12681/eadd/49026 ◽

2021 ◽

Author(s):

Ειρήνη Ζαχαροπούλου

Keyword(s):

Single Nucleotide Polymorphisms ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Rna Transcripts ◽

Non Coding Rna ◽

Genome Wide ◽

Non Coding Rnas

Ένας αυξανόμενος αριθμός μελετών ευρέως γονιδιώματος (Genome Wide Association Studies, GWAS) έχει αναδείξει εκατοντάδες πολυμορφισμούς που σχετίζονται με τον κίνδυνο εκδήλωσης ιδιοπαθών φλεγμονωδών νόσων του εντέρου (ΙΦΝΕ), όπως η νόσος Crohn (NC) και η ελκώδης κολίτιδα (ΕΚ). Πρόσφατα, έχει δειχθεί ότι τα μεγάλα μη-κωδικά RNA μετάγραφα (large non-coding RNA transcripts, LncRNAs) διαδραματίζουν ρυθμιστικό ρόλο σε ποικίλα νοσήματα, μεταβάλλοντας το επίπεδο έκφρασης των γονιδίων προκαλώντας εναλλακτικό μάτισμα ή επιδρώντας στη δευτεροταγή δομή τους, συμπεριλαμβανομένων των ΙΦΝΕ. Ωστόσο, η παθογένεση των ΙΦΝΕ παραμένει έως σήμερα ασαφής και υπάρχουν περιορισμένα δεδομένα σχετικά με το ρόλο των lncRNAs σε αυτές τις παθήσεις. Επομένως, στόχος της παρούσας μελέτης είναι να εκτιμήσει τη συσχέτιση μεταξύ πολυμορφισμών σε lncRNA γονίδια και την εκδήλωση ΙΦΝΕ στον ελληνικό πληθυσμό και να συμβάλει στην αποσαφήνιση της παθοφυσιολογίας των ΙΦΝΕ. Πραγματοποιήθηκε μελέτη πληθυσμού ασθενώνμαρτύρων και γονοτύπηση των πολυμορφισμών μονού νουκλεοτιδίου (single nucleotide polymorphisms, SNPs) rs1476514, rs3757247 και rs597325 σε δείγμα ορού αίματος από 242 ασθενείς με NC, 185 ασθενείς με ΕΚ και 220 υγιείς μάρτυρες.Βρέθηκε ότι η συχνότητα του αλληλόμορφου Α του SNP rs1476514 επικρατή στον υγιή πληθυσμό. Επιπροσθέτως, σχετικά με τον SNP rs3757247, η συχνότητα του αλληλόμορφου G είναι υψηλότερη στους υγιείς μάρτυρες σε σύγκριση με του ασθενείς με ΕΚ ενώ σε όλα τα υπό μελέτη δείγματα διαπιστώθηκε ετεροζυγωτία για τον SNP rs597325. Συμπερασματικά, η κατανόηση των μηχανισμών που συμμετέχουν στην εκδήλωση των ΙΦΝΕ είναι επί του παρόντος περιορισμένη και η αιτιολογία τους παραμένει άγνωστη. Καθώς όμως συσσωρεύονται δεδομένα που υποδεικνύουν ότι υπάρχει συσχέτιση ορισμένων SNPs σε lncRNAs με τις ΙΦΝΕ, θα χρειαστούν μελέτες με μεγαλύτερο πληθυσμό ώστε να επιβεβαιωθούν τα αποτελέσματα και να αναζητηθεί ο ρόλος των απορρυθμισμένων lncRNAs στην παθογένεση των ΙΦΝΕ.

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