Characterization and Analysis of Whole Transcriptome of Giant Panda Spleens: Implying Critical Roles of Long Non-Coding RNAs in Immunity

Background/Aims: Giant pandas, an endangered species, are a powerful symbol of species conservation. Giant pandas may suffer from a variety of diseases. Owing to their highly specialized diet of bamboo, giant pandas are thought to have a relatively weak ability to resist diseases. The spleen is the largest organ in the lymphatic system. However, there is little known about giant panda spleen at a molecular level. Thus, clarifying the regulatory mechanisms of spleen could help us further understand the immune system of the giant panda as well as its conservation. Methods: The two giant panda spleens were from two male individuals, one newborn and one an adult, in a non-pathological condition. The whole transcriptomes of mRNA, lncRNA, miRNA, and circRNA in the two spleens were sequenced using the Illumina HiSeq platform. EBseq and IDEG6 were used to observe the differentially expressed genes (DEGs) between these two spleens. Gene Ontology and KEGG analyses were used to annotate the function of DEGs. Furthermore, networks between non-coding RNAs and protein-coding genes were constructed to investigate the relationship between non-coding RNAs and immune-associated genes. Results: By comparative analysis of the whole transcriptomes of these two spleens, we found that one of the major roles of lncRNAs could be involved in the regulation of immune responses of giant panda spleens. In addition, our results also revealed that microRNAs and circRNAs may have evolved to regulate a large set of biological processes of giant panda spleens, and circRNAs may function as miRNA sponges. Conclusion: To our knowledge, this is the first report of lncRNAs and circRNAs in giant panda, which could be a useful resource for further giant panda research. Our study reveals the potential functional roles of miRNAs, lncRNAs, and circRNAs in giant panda spleen.

Download Full-text

Investigation of long non-coding RNAs as regulatory players of grapevine response to powdery and downy mildew infection

BMC Plant Biology ◽

10.1186/s12870-021-03059-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Garima Bhatia ◽

Santosh K. Upadhyay ◽

Anuradha Upadhyay ◽

Kashmir Singh

Keyword(s):

Downy Mildew ◽

Plasmopara Viticola ◽

Defense Responses ◽

Protein Coding ◽

Functional Roles ◽

Real Time Quantitative Pcr ◽

Transcriptional Reprogramming ◽

Sequencing Technologies ◽

Non Coding Rnas ◽

Fungal Phytopathogens

Abstract Background Long non-coding RNAs (lncRNAs) are regulatory transcripts of length > 200 nt. Owing to the rapidly progressing RNA-sequencing technologies, lncRNAs are emerging as considerable nodes in the plant antifungal defense networks. Therefore, we investigated their role in Vitis vinifera (grapevine) in response to obligate biotrophic fungal phytopathogens, Erysiphe necator (powdery mildew, PM) and Plasmopara viticola (downy mildew, DM), which impose huge agro-economic burden on grape-growers worldwide. Results Using computational approach based on RNA-seq data, 71 PM- and 83 DM-responsive V. vinifera lncRNAs were identified and comprehensively examined for their putative functional roles in plant defense response. V. vinifera protein coding sequences (CDS) were also profiled based on expression levels, and 1037 PM-responsive and 670 DM-responsive CDS were identified. Next, co-expression analysis-based functional annotation revealed their association with gene ontology (GO) terms for ‘response to stress’, ‘response to biotic stimulus’, ‘immune system process’, etc. Further investigation based on analysis of domains, enzyme classification, pathways enrichment, transcription factors (TFs), interactions with microRNAs (miRNAs), and real-time quantitative PCR of lncRNAs and co-expressing CDS pairs suggested their involvement in modulation of basal and specific defense responses such as: Ca2+-dependent signaling, cell wall reinforcement, reactive oxygen species metabolism, pathogenesis related proteins accumulation, phytohormonal signal transduction, and secondary metabolism. Conclusions Overall, the identified lncRNAs provide insights into the underlying intricacy of grapevine transcriptional reprogramming/post-transcriptional regulation to delay or seize the living cell-dependent pathogen growth. Therefore, in addition to defense-responsive genes such as TFs, the identified lncRNAs can be further examined and leveraged to candidates for biotechnological improvement/breeding to enhance fungal stress resistance in this susceptible fruit crop of economic and nutritional importance.

Download Full-text

393 DECONVOLUTING THE COMPLEXITY OF LONG NON-CODING RNAS AND ESOPHAGEAL CARCINOMA FOR POTENTIAL CLINICAL IMPLICATIONS

Diseases of the Esophagus ◽

10.1093/dote/doab052.393 ◽

2021 ◽

Vol 34 (Supplement_1) ◽

Author(s):

Siyuan Luan ◽

Yushang Yang ◽

Shouyue Zhang ◽

Xiaoxi Zeng ◽

Xin Xiao ◽

...

Keyword(s):

Esophageal Carcinoma ◽

Rapid Development ◽

Direct Interaction ◽

Clinical Applications ◽

Regulatory Mechanisms ◽

Protein Coding ◽

Functional Roles ◽

Cancer Hallmarks ◽

Clinical Scenarios ◽

Non Coding Rnas

Abstract Long non-coding RNAs (lncRNAs), a type of transcriptional products with more than 200 nucleotides in length, have been less characterized compared to protein-coding RNAs so far. However, it is increasingly evident that lncRNAs are key players involved in multiple genetic and epigenetic activities during the carcinogenesis of neoplastic diseases. Currently, accumulating data have pointed out the close connection between lncRNAs and esophageal carcinoma (EC), shedding light on further unravelling the complexity of lncRNAs and EC. Methods In this review, we thoroughly collect the evidence regarding original studies on EC-related lncRNAs by searching in MEDLINE/PubMed, Embase and WOS/SCI. We especially focus on summarizing EC-related lncRNAs based upon more updated evidence, and further discuss their different features from various perspectives, including regulatory mechanisms, functional roles in cancer hallmarks, as well as potential diagnostic and therapeutic applications, which would together reveal the complexity of lncRNAs and EC for potential clinical applications. Results We discuss over thirty EC-related lncRNAs in total, most of which function as oncogenes that promote cancer development, while the others function as tumor suppressors. Regulatory mechanisms included sponging miRNAs, direct interaction with proteins, and exosome visicle-based intercellular communication. Based upon these modes of actions, lncRNAs play multiple roles in cancer hallmarks such as uncontrolled cell growth, evasion of programmed cell death, invasion and metastasis. Moreover, lncRNAs packaged in exosomes have unique potency to serve as diagnostic biomarkers; some lncRNAs show great potential to predict patients' chemical resistance and may be crucial targets to improve chemoradiotherapy and targeted therapy. Conclusion Over the past few years, the research of EC-related lncRNAs maintain obviously rapid development, yet further exploration of exact mechanisms and clinical applications that lncRNAs can offer need to be done. Indeed, LncRNAs hold the promise of being applied in multiple clinical scenarios, especially early diagnosis of EC, improvement of sensitivity to chemotherapy/radiotherapy, and development of small-molecule targeted drugs.

Download Full-text

Long Non-Coding RNAs and Related Molecular Pathways in the Pathogenesis of Epilepsy

International Journal of Molecular Sciences ◽

10.3390/ijms20194898 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4898 ◽

Cited By ~ 5

Author(s):

Villa ◽

Lavitrano ◽

Combi

Keyword(s):

Biological Processes ◽

Complete Understanding ◽

Aberrant Expression ◽

Protein Coding ◽

Diagnostic Biomarkers ◽

Functional Roles ◽

The Central Nervous System ◽

Non Coding Rnas ◽

Underlying Mechanisms ◽

Coding Capacity

Epilepsy represents one of the most common neurological disorders characterized by abnormal electrical activity in the central nervous system (CNS). Recurrent seizures are the cardinal clinical manifestation. Although it has been reported that the underlying pathological processes include inflammation, changes in synaptic strength, apoptosis, and ion channels dysfunction, currently the pathogenesis of epilepsy is not yet completely understood. Long non-coding RNAs (lncRNAs), a class of long transcripts without protein-coding capacity, have emerged as regulatory molecules that are involved in a wide variety of biological processes. A growing number of studies reported that lncRNAs participate in the regulation of pathological processes of epilepsy and they are dysregulated during epileptogenesis. Moreover, an aberrant expression of lncRNAs linked to epilepsy has been observed both in patients and in animal models. In this review, we summarize latest advances concerning the mechanisms of action and the involvement of the most dysregulated lncRNAs in epilepsy. However, the functional roles of lncRNAs in the disease pathogenesis are still to be explored and we are only at the beginning. Additional studies are needed for the complete understanding of the underlying mechanisms and they would result in the use of lncRNAs as diagnostic biomarkers and novel therapeutic targets.

Download Full-text

Effect of an lncRNA-associated ceRNA regulatory network in MVI-positive hepatocellular carcinoma on their sensitivity to sorafenib.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16615 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16615-e16615

Author(s):

Zhiwen Luo ◽

Xinyu Bi

Keyword(s):

Hepatocellular Carcinoma ◽

Expression Profiles ◽

Recurrence Risk ◽

Vital Role ◽

Prognostic Biomarkers ◽

Protein Coding ◽

Functional Roles ◽

Cerna Network ◽

Mirna Sponges ◽

Regulate Protein

e16615 Background: Microvascular invasion (MVI) is a histological feature of hepatocellular carcinoma (HCC) related to aggressiveness. But different sensitivity to first line targeted drug, sorafenib, in MVI+ HCC has been observed. Long noncoding RNAs (lncRNAs) can act as microRNA (miRNA) sponges to regulate protein-coding gene expression; so lncRNAs are considered as a major part of competitive endogenous RNA (ceRNA) network and have attracted growing attention. We explored the regulatory mechanisms and functional roles of lncRNAs as ceRNAs in MVI+ HCC, and ceRNA network’s potential impact on prognosis and sensitivity to sorafenib in MVI+ HCC patient. Methods: We studied the expression profiles, prognostic value of lncRNA, miRNA, and mRNA from MVI+ HCC patients, established a prognosis-related network of dysregulated ceRNAs and analyzed its role in sensitivity to sorafenib and radiomics features by bioinformatics methods. Results: A ceRNA network including 13 lncRNAs, 3 miRNAs, and 2 mRNAs specific to MVI+ HCC was established. 6 lncRNAs ( ARHGEF7-AS1, ATP2B2-IT1, LINC00330, MUC2, TLR8-AS1 and ZNF385D-AS1), 2 miRNAs ( hsa-mir-206 and hsa-mir-373) and two mRNAs ( PAX3, SIK1) were prognostic biomarkers for MVI+ HCC. PAX3 was an unfavorable prognostic gene (HR = 1.9, 95%CI 1.01 ~ 3.60), while SIK1 favored the prognosis (HR = 0.4, 95%CI 0.19 ~ 0.85). PAX3 as a stratification in recurrence predicting model was used to identify MVI+ HCC with high or low recurrence risk. Datamining into the dataset of phase 3 STORM trial showed no difference in the influence of PAX3 level on the outcome between sorafenib HCC group and placebo HCC group. However, deep datamining into GDSC dataset revealed our high PAX3 group in MVI+ HCC related to resistance to sorafenib ( P = 0.0039). Radiomics features were extracted from CT of MVI+ HCC, and texture analysis in MVI+ HCCs is ongoing. Conclusions: The proposed ceRNA network may help elucidate the regulatory mechanism by which lncRNAs function as ceRNAs and contribute to the pathogenesis of MVI in HCC. Importantly, the candidate lncRNAs, miRNAs, and mRNAs involved in the ceRNA network have shown to be potential therapeutic targets and prognostic biomarkers for MVI+ HCC. PAX3 might play a vital role in the mechanism of sorafenib resistance in MVI+ HCC, exclusively, this aggressive HCC subtype. The ongoing experiments on radiomics might add potent supports to identify sorafenib sensitive MVI+ HCC.

Download Full-text

Characterisation and functional predictions of canine long non-coding RNAs

10.1101/303966 ◽

2018 ◽

Author(s):

Céline Le Béguec ◽

Valentin Wucher ◽

Lætitia Lagoutte ◽

Edouard Cadieu ◽

Nadine Botherel ◽

...

Keyword(s):

Expression Profiles ◽

Expression Patterns ◽

Regulatory Elements ◽

Domestic Dog ◽

Tissue Type ◽

Protein Coding ◽

Functional Roles ◽

Integrative Study ◽

Non Coding Rnas ◽

Biological Functionality

AbstractLong non-coding RNAs (lncRNAs) are a family of heterogeneous RNAs that play major roles in multiple biological processes. We recently identified an extended repertoire of more than 10,000 lncRNAs of the domestic dog however, predicting their biological functionality remains challenging. In this study, we have characterised the expression profiles of 10,444 canine lncRNAs in 26 distinct tissue types, representing various anatomical systems. We showed that lncRNA expressions are mainly clustered by tissue type and we highlighted that 44% of canine lncRNAs are expressed in a tissue-specific manner. We further demonstrated that tissue-specificity correlates with specific families of canine transposable elements. In addition, we identified more than 900 conserved dog-human lncRNAs for which we show their overall reproducible expression patterns between dog and humans through comparative transcriptomics. Finally, co-expression analyses of lncRNA and neighbouring protein-coding genes identified more than 3,400 canine lncRNAs, suggesting that functional roles of these lncRNAs act as regulatory elements. Altogether, this genomic and transcriptomic integrative study of lncRNAs constitutes a major resource to investigate genotype to phenotype relationships and biomedical research in the dog species.

Download Full-text

Functional Roles and Biological Mechanisms of Circular RNAs and Their Encoded Peptides in Glioma: A Narrative Review

International Clinical Neuroscience Journal ◽

10.34172/icnj.2021.33 ◽

2021 ◽

Vol 8 (4) ◽

pp. 157-167

Author(s):

Seyedeh Zahra Bakhti ◽

Sana Dadashi ◽

Anahita Dah Pahlevan ◽

Fatemeh Kafshresan

Keyword(s):

Rna Binding ◽

Rna Binding Proteins ◽

Current Knowledge ◽

Expression Patterns ◽

Circular Rnas ◽

Specific Expression ◽

Diagnostic Biomarkers ◽

Functional Roles ◽

Non Coding Rnas ◽

Mirna Sponges

Circular RNAs (circRNAs) are a complicated class of non-coding RNAs that have a covalently closed loop structure and are very stable and cautious. Multiple biological processes of malignancy, including tumorigenesis, development, invasion, metastasis, apoptosis, and vascularization, are disrupted by an increased number of circRNAs. Recent research has showed that circRNAs, functioning as microRNA (miRNA) sponges or protein scaffolds, interacting with RNA-binding proteins (RBPs), and autophagy regulators, affect the transcription and splicing regulation. Many circRNAs have tissue-specific expression patterns and are heavily conserved. CircRNA levels in neurons are dynamically modulated. Growing evidence suggests that circRNAs are highly abundant in neural tissues, perhaps owing to the proliferation of particular genes that promote circularization, implying that circRNA dysregulation is linked to nervous system disorders including glioma. The most widespread and deadly primary malignant brain tumor is glioma. CircRNA has a close connection to glioma, according to reported research. Here, the current knowledge about the properties of circRNAs is introduced and the biological and molecular functions of circRNAs are described. Then, the clinical association of circRNAs with glioma/glioblastoma and their level of expression and their regulatory mechanisms in tumorigenesis are discussed. Moreover, the potential of circRNAs as diagnostic biomarkers and predictors of brain cancer risk and possible therapeutic targets in medicine is examined.

Download Full-text

Non-Coding RNAs as Prognostic Markers for Endometrial Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22063151 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3151 ◽

Cited By ~ 2

Author(s):

Roberto Piergentili ◽

Simona Zaami ◽

Anna Franca Cavaliere ◽

Fabrizio Signore ◽

Giovanni Scambia ◽

...

Keyword(s):

Endometrial Cancer ◽

Prognostic Markers ◽

Classification Systems ◽

Prognostic Role ◽

Protein Coding ◽

Pathological Characteristics ◽

Epigenetic Events ◽

Cancer Types ◽

Non Coding Rnas

Endometrial cancer (EC) has been classified over the years, for prognostic and therapeutic purposes. In recent years, classification systems have been emerging not only based on EC clinical and pathological characteristics but also on its genetic and epigenetic features. Noncoding RNAs (ncRNAs) are emerging as promising markers in several cancer types, including EC, for which their prognostic value is currently under investigation and will likely integrate the present prognostic tools based on protein coding genes. This review aims to underline the importance of the genetic and epigenetic events in the EC tumorigenesis, by expounding upon the prognostic role of ncRNAs.

Download Full-text

Upregulation of LINC01426 promotes the progression and stemness in lung adenocarcinoma by enhancing the level of SHH protein to activate the hedgehog pathway

Cell Death and Disease ◽

10.1038/s41419-021-03435-y ◽

2021 ◽

Vol 12 (2) ◽

Author(s):

Xiaoli Liu ◽

Zuwei Yin ◽

Linping Xu ◽

Huaimin Liu ◽

Lifeng Jiang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Bioinformatics Analysis ◽

Epithelial Mesenchymal Transition ◽

Mrna Level ◽

Hedgehog Pathway ◽

Biological Processes ◽

Protein Coding ◽

Mesenchymal Transition ◽

Functional Roles ◽

Rip Assay

AbstractLong noncoding RNAs (lncRNAs) play crucial roles in regulating a variety of biological processes in lung adenocarcinoma (LUAD). In our study, we mainly explored the functional roles of a novel lncRNA long intergenic non-protein coding RNA 1426 (LINC01426) in LUAD. We applied bioinformatics analysis to find the expression of LINC01426 was upregulated in LUAD tissue. Functionally, silencing of LINC01426 obviously suppressed the proliferation, migration, epithelial–mesenchymal transition (EMT), and stemness of LUAD cells. Then, we observed that LINC01426 functioned through the hedgehog pathway in LUAD. The effect of LINC01426 knockdown could be fully reversed by adding hedgehog pathway activator SAG. In addition, we proved that LINC01426 could not affect SHH transcription and its mRNA level. Pull-down sliver staining and RIP assay revealed that LINC01426 could interact with USP22. Ubiquitination assays manifested that LINC01426 and USP22 modulated SHH ubiquitination levels. Rescue assays verified that SHH overexpression rescued the cell growth, migration, and stemness suppressed by LINC01426 silencing. In conclusion, LINC01426 promotes LUAD progression by recruiting USP22 to stabilize SHH protein and thus activate the hedgehog pathway.

Download Full-text

RNA sequencing of transcriptomes in human brain regions: protein-coding and non-coding RNAs, isoforms and alleles

BMC Genomics ◽

10.1186/s12864-015-2207-8 ◽

2015 ◽

Vol 16 (1) ◽

Cited By ~ 14

Author(s):

Amy Webb ◽

Audrey C. Papp ◽

Amanda Curtis ◽

Leslie C. Newman ◽

Maciej Pietrzak ◽

...

Keyword(s):

Human Brain ◽

Rna Sequencing ◽

Brain Regions ◽

Protein Coding ◽

Non Coding Rnas

Download Full-text

CALINCA—A Novel Pipeline for the Identification of lncRNAs in Podocyte Disease

Cells ◽

10.3390/cells10030692 ◽

2021 ◽

Vol 10 (3) ◽

pp. 692

Author(s):

Sweta Talyan ◽

Samantha Filipów ◽

Michael Ignarski ◽

Magdalena Smieszek ◽

He Chen ◽

...

Keyword(s):

Cell Biology ◽

Mammalian Cells ◽

De Novo ◽

Depth Information ◽

Gene Products ◽

Classical Analysis ◽

Protein Coding ◽

Bioinformatic Pipeline ◽

Non Coding Rnas ◽

Filtration Unit

Diseases of the renal filtration unit—the glomerulus—are the most common cause of chronic kidney disease. Podocytes are the pivotal cell type for the function of this filter and focal-segmental glomerulosclerosis (FSGS) is a classic example of a podocytopathy leading to proteinuria and glomerular scarring. Currently, no targeted treatment of FSGS is available. This lack of therapeutic strategies is explained by a limited understanding of the defects in podocyte cell biology leading to FSGS. To date, most studies in the field have focused on protein-coding genes and their gene products. However, more than 80% of all transcripts produced by mammalian cells are actually non-coding. Here, long non-coding RNAs (lncRNAs) are a relatively novel class of transcripts and have not been systematically studied in FSGS to date. The appropriate tools to facilitate lncRNA research for the renal scientific community are urgently required due to a row of challenges compared to classical analysis pipelines optimized for coding RNA expression analysis. Here, we present the bioinformatic pipeline CALINCA as a solution for this problem. CALINCA automatically analyzes datasets from murine FSGS models and quantifies both annotated and de novo assembled lncRNAs. In addition, the tool provides in-depth information on podocyte specificity of these lncRNAs, as well as evolutionary conservation and expression in human datasets making this pipeline a crucial basis to lncRNA studies in FSGS.

Download Full-text