scholarly journals Evolutionary Patterns of Non-Coding RNA in Cardiovascular Biology

2019 ◽  
Vol 5 (1) ◽  
pp. 15 ◽  
Author(s):  
Shrey Gandhi ◽  
Frank Ruehle ◽  
Monika Stoll

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.

2020 ◽  
Vol 6 (3) ◽  
pp. 35
Author(s):  
Deepak Balamurali ◽  
Monika Stoll

Cardiovascular diseases (CVDs) are of multifactorial origin and can be attributed to several genetic and environmental components. CVDs are the leading cause of mortality worldwide and they primarily damage the heart and the vascular system. Non-coding RNA (ncRNA) refers to functional RNA molecules, which have been transcribed into DNA but do not further get translated into proteins. Recent transcriptomic studies have identified the presence of thousands of ncRNA molecules across species. In humans, less than 2% of the total genome represents the protein-coding genes. While the role of many ncRNAs is yet to be ascertained, some long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been associated with disease progression, serving as useful diagnostic and prognostic biomarkers. A plethora of data repositories specialized in ncRNAs have been developed over the years using publicly available high-throughput data from next-generation sequencing and other approaches, that cover various facets of ncRNA research like basic and functional annotation, expressional profile, structural and molecular changes, and interaction with other biomolecules. Here, we provide a compendium of the current ncRNA databases relevant to cardiovascular research.


2018 ◽  
Vol 45 (3) ◽  
pp. 1191-1204 ◽  
Author(s):  
JingJing Wu ◽  
Swei Sunny Hann

Nasopharyngeal carcinoma (NPC) is one of the most common cancers originating in the nasopharynx and occurring at high frequency in South-eastern Asia and North Africa. Long non-coding RNAs (lncRNAs) are a class of non-protein-coding RNA molecules and key regulators of developmental, physiological, and pathological processes in humans. Emerging studies have shown that lncRNAs play critical roles in tumorgenicity and cancer prognosis. With the development of deep sequencing analyses, an extensive amount of functional lncRNAs have been discovered in nasopharyngeal carcinoma tissues and cell lines. However, the roles and mechanisms of aberrantly expressed lncRNAs in the pathogenesis of NPC are not fully understood. In this review, we briefly illustrate the concept, identification, functional characterization, and summarize recent advancements of biological functions of lncRNAs with heterogeneous mechanistic characterization and their involvement in NPC. Then, we describe individual lncRNAs that have been associated with tumorgenesis, growth, invasion, cancer stem cell differentiation, metastasis, drug resistance and discuss the strategies of their therapeutic manipulation in NPC. We also review the emerging insights into the role of lncRNAs and their potential as biomarkers and therapeutic targets for novel treatment paradigms. Finally, we highlight the up-to-date of clinical information involving lncRNAs and future directions in the linking lncRNAs to potential gene therapies, and how modifications of lncRNAs can be exploited for prevention and treatment of NPC.


Author(s):  
Yolan J. Reckman ◽  
Yigal M. Pinto

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.


2021 ◽  
Author(s):  
David Staněk

Abstract In this review I focus on the role of splicing in long non-coding RNA (lncRNA) life. First, I summarize differences between the splicing efficiency of protein-coding genes and lncRNAs and discuss why non-coding RNAs are spliced less efficiently. In the second half of the review, I speculate why splice sites are the most conserved sequences in lncRNAs and what additional roles could splicing play in lncRNA metabolism. I discuss the hypothesis that the splicing machinery can, besides its dominant role in intron removal and exon joining, protect cells from undesired transcripts.


Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770365 ◽  
Author(s):  
Fangyuan Jing ◽  
Huicheng Jin ◽  
Yingying Mao ◽  
Yingjun Li ◽  
Ye Ding ◽  
...  

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.


2021 ◽  
Vol 22 (3) ◽  
pp. 1166
Author(s):  
Vincenzo De Falco ◽  
Stefania Napolitano ◽  
Daniela Esposito ◽  
Luigi Pio Guerrera ◽  
Davide Ciardiello ◽  
...  

Cutaneous melanoma is considered a rare tumor, although it is one of the most common cancers in young adults and its incidence has risen in the last decades. Targeted therapy, with BRAF and MEK inhibitors, and immunotherapy revolutionized the treatment of metastatic melanoma but there is still a considerable percentage of patients with primary or acquired resistance to these therapies. Recently, oncology researchers directed their attention at the role of long non-coding RNAs (lncRNAs) in different types of cancers, including melanoma. lncRNAs are RNA transcripts, initially considered “junk sequences”, that have been proven to have a crucial role in the fine regulation of physiological and pathological processes of different tissues. Furthermore, they are more expressed in tumors than protein-coding genes, constituting perfect candidates either as biomarkers (diagnostic, prognostic, predictive) or as therapeutic targets. In this work, we reviewed all the literature available for lncRNA in melanoma, elucidating all the potential roles in this tumor.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jiawen Li ◽  
Yulin Zhang ◽  
Donghui Zhang ◽  
Yifei Li

Sepsis is a syndrome with life-threatening organ dysfunction induced by a dysregulated host response to infection. The heart is one of the most commonly involved organs during sepsis, and cardiac dysfunction, which is usually indicative of an extremely poor clinical outcome, is a leading cause of death in septic cases. Despite substantial improvements in the understanding of the mechanisms that contribute to the origin and responses to sepsis, the prognosis of sepsis-induced cardiac dysfunction (SICD) remains poor and its molecular pathophysiological changes are not well-characterized. The recently discovered group of mediators known as long non-coding RNAs (lncRNAs) have presented novel insights and opportunities to explore the mechanisms and development of SICD and may provide new targets for diagnosis and therapeutic strategies. LncRNAs are RNA transcripts of more than 200 nucleotides with limited or no protein-coding potential. Evidence has rapidly accumulated from numerous studies on how lncRNAs function in associated regulatory circuits during SICD. This review outlines the direct evidence of the effect of lncRNAs on SICD based on clinical trials and animal studies. Furthermore, potential functional lncRNAs in SICD that have been identified in sepsis studies are summarized with a proven biological function in research on other cardiovascular diseases.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Wei Zuo ◽  
Wei Zhang ◽  
Fei Xu ◽  
Jing Zhou ◽  
Wei Bai

Abstract Background Long non-coding RNAs (lncRNAs) are a family of non-protein-coding RNAs, which have the ability to influence the chemo-resistance of lung adenocarcinoma (LAC). In this study, we explored the mechanism by which LINC00485 competitively binds to microRNA-195 (miR-195) in the regulation of the chemotherapy sensitivity in LAC by regulating checkpoint kinase 1 (CHEK1). Methods Microarray analysis was used to screen out LAC related genes, and interaction between CHEK1 and miR-195, as well as that between miR-195 and LINC00485, was further confirmed by RNA-pull down and RIP. LINC00485 expression in LAC cells (A549 and H1299) was determined. The cells were then introduced with miR-195, anta-miR-195, LINC00485 or si-LINC00485 to identify the role of miR-195 and LINC00485 in LAC through evaluating the expression of CHEK1, CHEK1, Bax, Bcl-2, VEGF and HIF-1α in LAC cells by either RT-qPCR or Western blot analysis. After being treated with different concentration of cisplatin, cell proliferation, colony formation and apoptosis were assessed. Results LINC00485 acted as a competitive endogenous RNA against miR-195, and miR-195 directly targeted CHEK1. The expression of LINC00485 was higher in LAC cells. The down-regulation of LINC00485 or the up-regulation of miR-195 decreased the expression of CHEK1, Bcl-2, VEGF and HIF-1α, while also increasing the expression of Bax. Moreover, the over-expression of miR-195, or the silencing of LINC00485 enhanced the sensitivity of LAC cells to cisplatin, thereby promoting the apoptosis of LAC cells while suppressing the proliferation. Conclusion LINC00485 competitively binds to miR-195 to elevate CHEK1 expression in LAC cells, suggesting that LINC00485 is a novel direction for therapeutic strategies of LAC.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Min Lu ◽  
Xinglei Qin ◽  
Yajun Zhou ◽  
Gang Li ◽  
Zhaoyang Liu ◽  
...  

AbstractGemcitabine is the first-line chemotherapy drug for cholangiocarcinoma (CCA), but acquired resistance has been frequently observed in CCA patients. To search for potential long noncoding RNAs (lncRNAs) involved in gemcitabine resistance, two gemcitabine resistant CCA cell lines were established and dysregulated lncRNAs were identified by lncRNA microarray. Long intergenic non-protein coding RNA 665 (LINC00665) were found to rank the top 10 upregulated lncRNAs in our study, and high LINC00665 expression was closely associated with poor prognosis and chemoresistance of CCA patients. Silencing LINC00665 in gemcitabine resistant CCA cells impaired gemcitabine tolerance, while enforced LINC00665 expression increased gemcitabine resistance of sensitive CCA cells. The gemcitabine resistant CCA cells showed increased EMT and stemness properties, and silencing LINC00665 suppressed sphere formation, migration, invasion and expression of EMT and stemness markers. In addition, Wnt/β-Catenin signaling was activated in gemcitabine resistant CCA cells, but LINC00665 knockdown suppressed Wnt/β-Catenin activation. B-cell CLL/lymphoma 9-like (BCL9L), the nucleus transcriptional regulators of Wnt/β-Catenin signaling, plays a key role in the nucleus translocation of β-Catenin and promotes β-Catenin-dependent transcription. In our study, we found that LINC00665 regulated BCL9L expression by acting as a molecular sponge for miR-424-5p. Moreover, silencing BCL9L or miR-424-5p overexpression suppressed gemcitabine resistance, EMT, stemness and Wnt/β-Catenin activation in resistant CCA cells. In conclusion, our results disclosed the important role of LINC00665 in gemcitabine resistance of CCA cells, and provided a new biomarker or therapeutic target for CCA treament.


2021 ◽  
Vol 22 (6) ◽  
pp. 3151 ◽  
Author(s):  
Roberto Piergentili ◽  
Simona Zaami ◽  
Anna Franca Cavaliere ◽  
Fabrizio Signore ◽  
Giovanni Scambia ◽  
...  

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.


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