scholarly journals Challenges and Strategies in Ascribing Functions to Long Noncoding RNAs

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1458 ◽  
Author(s):  
Yang Zhao ◽  
Hongqi Teng ◽  
Fan Yao ◽  
Shannon Yap ◽  
Yutong Sun ◽  
...  

Long noncoding RNAs (lncRNAs) are involved in many physiological and pathological processes, such as development, aging, immunity, and cancer. Mechanistically, lncRNAs exert their functions through interaction with proteins, genomic DNA, and other RNA, leading to transcriptional and post-transcriptional regulation of gene expression, either in cis or in trans; it is often difficult to distinguish between these two regulatory mechanisms. A variety of approaches, including RNA interference, antisense oligonucleotides, CRISPR-based methods, and genetically engineered mouse models, have yielded abundant information about lncRNA functions and underlying mechanisms, albeit with many discrepancies. In this review, we elaborate on the challenges in ascribing functions to lncRNAs based on the features of lncRNAs, including the genomic location, copy number, domain structure, subcellular localization, stability, evolution, and expression pattern. We also describe a framework for the investigation of lncRNA functions and mechanisms of action. Rigorous characterization of cancer-implicated lncRNAs is critical for the identification of bona fide anticancer targets.

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Guangbing Li ◽  
Haohai Zhang ◽  
Xueshuai Wan ◽  
Xiaobo Yang ◽  
Chengpei Zhu ◽  
...  

Long noncoding RNAs (lncRNAs) have been attracting immense research interests. However, only a handful of lncRNAs had been thoroughly characterized. They were involved in fundamental cellular processes including regulation of gene expression at epigenetics as well as tumorogenesis. In this paper, we give a systematic and comprehensive review of existing literature about lncRNA involvement in hepatocellular carcinoma. This review exhibited that lncRNAs played important roles in tumorigenesis and subsequent prognosis and metastasis of hepatocellular carcinoma and elucidated the role of some specific lncRNAs such as MALAT1 and HOTAIR in the pathophysiology of hepatocellular carcinoma and their potential of being therapeutic targets.


2020 ◽  
Vol 15 (9) ◽  
pp. 577-593
Author(s):  
Rafeed Rahman Turjya ◽  
Md. Abdullah-Al-Kamran Khan ◽  
Abul Bashar Mir Md. Khademul Islam

Background: Regulatory roles of long noncoding RNAs (lncRNAs) during viral infection has become more evident in last decade, but are yet to be explored for SARS-CoV-2. Materials & methods: We analyzed RNA-seq dataset of SARS-CoV-2 infected lung epithelial cells to identify differentially expressed genes. Results: Our analyses uncover 21 differentially expressed lncRNAs broadly involved in cell survival and regulation of gene expression. These lncRNAs can directly interact with six differentially expressed protein-coding genes, and ten host genes that interact with SARS-CoV-2 proteins. Also, they can block the suppressive effect of nine microRNAs induced in viral infections. Conclusion: Our investigation determines that deregulated lncRNAs in SARS-CoV-2 infection are involved in viral proliferation, cellular survival, and immune response, ultimately determining disease outcome.


2020 ◽  
Vol 318 (5) ◽  
pp. H1308-H1315 ◽  
Author(s):  
Lee Toni ◽  
Frehiwet Hailu ◽  
Carmen C. Sucharov

Noncoding RNAs (ncRNAs) are broadly described as RNA molecules that are not translated into protein. The investigation of dysregulated ncRNAs in human diseases such as cancer, neurological, and cardiovascular diseases has been under way for well over a decade. Micro-RNAs and long noncoding RNAs (lncRNAs) are the best characterized ncRNAs. These ncRNAs can have profound effects on the regulation of gene expression during cardiac development and disease. Importantly, ncRNAs are significant regulators of gene expression in several congenital heart diseases and can positively or negatively impact cardiovascular development. In this review, we focus on literature involving micro-RNAs and lncRNAs in the context of pediatric cardiovascular diseases, preclinical models of heart failure, and cardiac development.


F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1771 ◽  
Author(s):  
Xu Zhang ◽  
Wenqian Hu

Mammalian development is under tight control to ensure precise gene expression. Recent studies reveal a new layer of regulation of gene expression mediated by long noncoding RNAs. These transcripts are longer than 200nt that do not have functional protein coding capacity. Interestingly, many of these long noncoding RNAs are expressed with high specificity in different types of cells, tissues, and developmental stages in mammals, suggesting that they may have functional roles in diverse biological processes. Here, we summarize recent findings of long noncoding RNAs in hematopoiesis, which is one of the best-characterized mammalian cell differentiation processes. Then we provide our own perspectives on future studies of long noncoding RNAs in this field.


2018 ◽  
Author(s):  
Iuliia K. Karnaukhova ◽  
Dmitrii E. Polev ◽  
Larisa L. Krukovskaya ◽  
Alexey E. Masharsky ◽  
Olga V. Nazarenko ◽  
...  

AbstractOrthopedia homeobox (OTP) gene encodes a homeodomain-containing transcription factor involved in brain development. OTP is mapped to human chromosome 5q14.1. Earlier we described transcription in the second intron of this gene in wide variety of tumors, but among normal tissues only in testis. In GeneBank these transcripts are presented by several 300-400 nucleotides long AI267901-like ESTs.We assumed that AI267901-like ESTs belong to longer transcript(s). We used the Rapid Amplification of cDNA Ends (RACE) approach and other methods to find the full-length transcript. The found transcript was 2436 nucleotides long polyadenylated sequence in antisense to OTP gene. The corresponding gene consisted of two exons separated by an intron of 2961 bp long. The first exon was found to be 91 bp long and located in the third exon of OTP gene. The second exon was 2345bp long and located in the second intron of OTP gene.The search of possible open reading frames (ORFs) showed the lack of significant ORFs. We have shown the expression of new gene in many human tumors and only in one sampled normal testis. The data suggest that we discovered a new antisense cancer-testis sequence OTP-AS1 (OTP- antisense RNA 1), which belongs to long noncoding RNAs (lncRNAs). According to our findings we assume that OTP-AS1 and OTP genes may be the CT-coding gene/CT-ncRNA pair involved in regulatory interactions.Author summaryPreviously, long non-coding RNAs (lncRNAs) were considered as genetic “noise”. However, it was later shown that only 2% of genomic transcripts have a protein-coding ability. Non-coding RNA is divided into short non-coding RNAs (20-200 nucleotides) and long noncoding RNAs (200-100,000 nucleotides). Genes encoding lncRNA often overlap or are adjacent to protein-coding genes, and localization of this kind is beneficial in order to regulate the transcription of neighboring genes. Studies have shown that of lncRNAs play many roles in the regulation of gene expression. New evidence indicates that dysfunctions of lncRNAs are associated with human diseases and cancer.In our study we found a new cancer-testis long noncoding RNA (OTP-AS1), which is an antisense of protein-coding cancer-testis gene (OTP). Thus, OTP-AS1 and OTP genes may be the CT-coding gene/CT-ncRNA pair involved in regulatory interactions. This is supported by the similar profile of their expression. OTP-AS1 may be of interest as a potential diagnostic marker of cancer or a potential target for cancer therapy.Part of OTP-AS1 gene (5’-end of the second exon) is evolutionary younger than the rest of gene sequence and is less conservative. This links OTP-AS1 gene with so-called TSEEN (tumor-specifically expressed, evolutionary novel) genes described by the authors in previous papers.


2021 ◽  
Vol 11 ◽  
Author(s):  
Jie Qin ◽  
Chuanlu Jiang ◽  
Jinquan Cai ◽  
Xiangqi Meng

Accompanying the development of biomedicine, our knowledge of glioma, one of the most common primary intracranial carcinomas, is becoming more comprehensive. Unfortunately, patients with glioblastoma (GBM) still have a dismal prognosis and a high relapse rate, even with standard combination therapy, namely, surgical resection, postoperative radiotherapy and chemotherapy. The absence of validated biomarkers is responsible for the majority of these poor outcomes, and reliable therapeutic targets are indispensable for improving the prognosis of patients suffering from gliomas. Identification of both precise diagnostic and accurate prognostic markers and promising therapeutic targets has therefore attracted considerable attention from researchers. Encouragingly, accumulating evidence has demonstrated that long noncoding RNAs (lncRNAs) play important roles in the pathogenesis and oncogenesis of various categories of human tumors, including gliomas. Nevertheless, the underlying mechanisms by which lncRNAs regulate diverse biological behaviors of glioma cells, such as proliferation, invasion and migration, remain poorly understood. Consequently, this review builds on previous studies to further summarize the progress in the field of lncRNA regulation of gliomas over recent years and addresses the potential of lncRNAs as diagnostic and prognostic markers and therapeutic targets.


2021 ◽  
Vol 12 ◽  
Author(s):  
Qinzhi Yang ◽  
Fang Lin ◽  
Yanan Wang ◽  
Min Zeng ◽  
Mao Luo

Coronavirus disease 2019 (COVID-19), which has high incidence rates with rapid rate of transmission, is a pandemic that spread across the world, resulting in more than 3,000,000 deaths globally. Currently, several drugs have been used for the clinical treatment of COVID-19, such as antivirals (radecivir, baritinib), monoclonal antibodies (tocilizumab), and glucocorticoids (dexamethasone). Accumulating evidence indicates that long noncoding RNAs (lncRNAs) are essential regulators of virus infections and antiviral immune responses including biological processes that are involved in the regulation of COVID-19 and subsequent disease states. Upon viral infections, cellular lncRNAs directly regulate viral genes and influence viral replication and pathology through virus-mediated changes in the host transcriptome. Additionally, several host lncRNAs could help the occurrence of viral immune escape by inhibiting type I interferons (IFN-1), while others could up-regulate IFN-1 production to play an antiviral role. Consequently, understanding the expression and function of lncRNAs during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection will provide insights into the development of lncRNA-based methods. In this review, we summarized the current findings of lncRNAs in the regulation of the strong inflammatory response, immune dysfunction and thrombosis induced by SARS-CoV-2 infection, discussed the underlying mechanisms, and highlighted the therapeutic challenges of COVID-19 treatment and its future research directions.


2021 ◽  
Vol 15 ◽  
pp. 117793222098850
Author(s):  
Mozhdeh Shahmoradi ◽  
Zahra Rezvani

Cutaneous melanoma is the most aggressive type of skin cancer which its incidence has significantly increased in recent years worldwide. Thus, more investigations are required to identify the underlying mechanisms of melanoma malignant transformation and metastasis. In this context, long noncoding RNAs (lncRNAs) are a new type of noncoding transcripts that their dysregulations are associated with almost all cancers including melanoma. However, the precise functional roles of most of the significantly altered lncRNAs in melanoma have not yet been fully inspected. In this study, a comprehensive list of lncRNAs was interrogated across cutaneous melanoma samples to identify the significantly altered/dysregulated lncRNAs. To this end, lncRNAs were filtered in several steps and the selected lncRNAs projected to a bioinformatic and systems biology analysis using several publicly available databases and tools such as GEPIA and cBioPortal. According to our results, 30 lncRNAs were notably altered/dysregulated in cutaneous melanoma most of which were co-expressed with each other. Also, co-expression/alteration and differential expression analyses led to the selection of 12 out of these 30 lncRNAs as cutaneous melanoma key lncRNAs. Furthermore, functional demonstrated that these 12 lncRNAs might be involved in melanoma-relevant biological processes and pathways. In addition, the end result of our analyses demonstrated that these lncRNAs are associated with the clinicopathological features of melanoma patients. These 12 lncRNAs need to be further investigated in future studies to characterize their exact roles in melanoma development and to identify their potential for being used as drug targets and/or biomarkers for cutaneous melanoma.


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