scholarly journals Long Non-Coding RNAs: The Regulatory Mechanisms, Research Strategies, and Future Directions in Cancers

2020 ◽  
Vol 10 ◽  
Author(s):  
Na Gao ◽  
Yueheng Li ◽  
Jing Li ◽  
Zhengfan Gao ◽  
Zhenzhen Yang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Tumor Development ◽  
Therapeutic Targets ◽  
Regulatory Mechanisms ◽  
Clinical Implementation ◽  
Research Strategies ◽  
Protein Coding ◽  
Functional Studies ◽  
Diagnosis And Prognosis ◽  
Non Coding Rnas

The development and application of whole genome sequencing technology has greatly broadened our horizons on the capabilities of long non-coding RNAs (lncRNAs). LncRNAs are more than 200 nucleotides in length and lack protein-coding potential. Increasing evidence indicates that lncRNAs exert an irreplaceable role in tumor initiation, progression, as well as metastasis, and are novel molecular biomarkers for diagnosis and prognosis of cancer patients. Furthermore, lncRNAs and the pathways they influence might represent promising therapeutic targets for a number of tumors. Here, we discuss the recent advances in understanding of the specific regulatory mechanisms of lncRNAs. We focused on the signal, decoy, guide, and scaffold functions of lncRNAs at the epigenetic, transcription, and post-transcription levels in cancer cells. Additionally, we summarize the research strategies used to investigate the roles of lncRNAs in tumors, including lncRNAs screening, lncRNAs characteristic analyses, functional studies, and molecular mechanisms of lncRNAs. This review will provide a short but comprehensive description of the lncRNA functions in tumor development and progression, thus accelerating the clinical implementation of lncRNAs as tumor biomarkers and therapeutic targets.

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

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.

scholarly journals Diagnostic and Prognostic Potential of Circulating Long Non-Coding RNAs in Non Small Cell Lung Cancer

2018 ◽  
Vol 49 (2) ◽  
pp. 816-827 ◽  
Author(s):  
Wei Peng ◽  
Jun Wang ◽  
Bin Shan ◽  
Zhenzi Peng ◽  
Yeping Dong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Protein Function ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Protein Coding ◽  
Cell Lung Carcinoma ◽  
Therapeutic Modalities ◽  
Diagnosis And Prognosis ◽  
Non Coding Rnas

Lung cancer is the leading cause of cancer-related mortality worldwide. Approximately 80% of lung cancer cases are non–small cell lung carcinoma (NSCLC). However current diagnostic and therapeutic modalities against NSCLC are ineffective due to incomplete understanding of molecular pathogenesis of NSCLC. Emerging evidence shows that long non-coding RNAs (lncRNAs) can function as biomarkers for diagnosis and prognosis. LncRNAs can control transcription, translation, and protein function via diverse mechanisms although they lack the protein coding potential. LncRNAs have attracted intense investigations on their roles in cancer. Mounting evidence indicates that lncRNAs are promising biomarkers in diagnosis and prognosis for NSCLC, especially their presence in body fluids. Herein we will review recent advances in the research that explores the diagnostic and prognostic potentials of lncRNAs in NSCLC. We will also discuss emerging evidence that suggested lncRNAs as therapeutic targets in NSCLC.

scholarly journals LncTarD: a manually-curated database of experimentally-supported functional lncRNA–target regulations in human diseases

2019 ◽  
Author(s):  
Hongying Zhao ◽  
Jian Shi ◽  
Yunpeng Zhang ◽  
Aimin Xie ◽  
Lei Yu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Sequence Data ◽  
Human Diseases ◽  
Regulatory Mechanisms ◽  
Biological Functions ◽  
Functional Dynamics ◽  
Disease Associations ◽  
Non Coding Rnas ◽  
User Friendly ◽  
Pan Cancer

Abstract Long non-coding RNAs (lncRNAs) are associated with human diseases. Although lncRNA–disease associations have received significant attention, no online repository is available to collect lncRNA-mediated regulatory mechanisms, key downstream targets, and important biological functions driven by disease-related lncRNAs in human diseases. We thus developed LncTarD (http://biocc.hrbmu.edu.cn/LncTarD/ or http://bio-bigdata.hrbmu.edu.cn/LncTarD), a manually-curated database that provides a comprehensive resource of key lncRNA–target regulations, lncRNA-influenced functions, and lncRNA-mediated regulatory mechanisms in human diseases. LncTarD offers (i) 2822 key lncRNA–target regulations involving 475 lncRNAs and 1039 targets associated with 177 human diseases; (ii) 1613 experimentally-supported functional regulations and 1209 expression associations in human diseases; (iii) important biological functions driven by disease-related lncRNAs in human diseases; (iv) lncRNA–target regulations responsible for drug resistance or sensitivity in human diseases and (v) lncRNA microarray, lncRNA sequence data and transcriptome data of an 11 373 pan-cancer patient cohort from TCGA to help characterize the functional dynamics of these lncRNA–target regulations. LncTarD also provides a user-friendly interface to conveniently browse, search, and download data. LncTarD will be a useful resource platform for the further understanding of functions and molecular mechanisms of lncRNA deregulation in human disease, which will help to identify novel and sensitive biomarkers and therapeutic targets.

scholarly journals LncExpDB: an expression database of human long non-coding RNAs

2020 ◽  
Vol 49 (D1) ◽  
pp. D962-D968 ◽  
Author(s):  
Zhao Li ◽  
Lin Liu ◽  
Shuai Jiang ◽  
Qianpeng Li ◽  
Changrui Feng ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Biological Functions ◽  
Protein Coding ◽  
Web Interfaces ◽  
Functional Studies ◽  
Protein Coding Genes ◽  
Genes Expression ◽  
Wide Range ◽  
Non Coding Rnas ◽  
User Friendly

Abstract Expression profiles of long non-coding RNAs (lncRNAs) across diverse biological conditions provide significant insights into their biological functions, interacting targets as well as transcriptional reliability. However, there lacks a comprehensive resource that systematically characterizes the expression landscape of human lncRNAs by integrating their expression profiles across a wide range of biological conditions. Here, we present LncExpDB (https://bigd.big.ac.cn/lncexpdb), an expression database of human lncRNAs that is devoted to providing comprehensive expression profiles of lncRNA genes, exploring their expression features and capacities, identifying featured genes with potentially important functions, and building interactions with protein-coding genes across various biological contexts/conditions. Based on comprehensive integration and stringent curation, LncExpDB currently houses expression profiles of 101 293 high-quality human lncRNA genes derived from 1977 samples of 337 biological conditions across nine biological contexts. Consequently, LncExpDB estimates lncRNA genes’ expression reliability and capacities, identifies 25 191 featured genes, and further obtains 28 443 865 lncRNA-mRNA interactions. Moreover, user-friendly web interfaces enable interactive visualization of expression profiles across various conditions and easy exploration of featured lncRNAs and their interacting partners in specific contexts. Collectively, LncExpDB features comprehensive integration and curation of lncRNA expression profiles and thus will serve as a fundamental resource for functional studies on human lncRNAs.

scholarly journals Long non-coding RNAs in plants: emerging modulators of gene activity in development and stress responses

Planta ◽  
2020 ◽  
Vol 252 (5) ◽  
Author(s):  
Li Chen ◽  
Qian-Hao Zhu ◽  
Kerstin Kaufmann
Keyword(s):  
Stress Responses ◽  
Translational Regulation ◽  
Molecular Mechanisms ◽  
Functional Characterization ◽  
Reproductive Organs ◽  
Gene Activity ◽  
Protein Coding ◽  
Wide Range ◽  
Non Coding Rnas ◽  
Coding Potential

Abstract Main conclusion Long non-coding RNAs modulate gene activity in plant development and stress responses by various molecular mechanisms. Abstract Long non-coding RNAs (lncRNAs) are transcripts larger than 200 nucleotides without protein coding potential. Computational approaches have identified numerous lncRNAs in different plant species. Research in the past decade has unveiled that plant lncRNAs participate in a wide range of biological processes, including regulation of flowering time and morphogenesis of reproductive organs, as well as abiotic and biotic stress responses. LncRNAs execute their functions by interacting with DNA, RNA and protein molecules, and by modulating the expression level of their targets through epigenetic, transcriptional, post-transcriptional or translational regulation. In this review, we summarize characteristics of plant lncRNAs, discuss recent progress on understanding of lncRNA functions, and propose an experimental framework for functional characterization.

scholarly journals Emerging Role of Long Non-Coding RNAs in Diabetic Vascular Complications

2021 ◽  
Vol 12 ◽  
Author(s):  
Vinay Singh Tanwar ◽  
Marpadga A. Reddy ◽  
Rama Natarajan
Keyword(s):  
Drug Targets ◽  
Molecular Mechanisms ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
Protein Coding ◽  
Altered Expression ◽  
Diabetic Vascular Complications ◽  
Obesity And Diabetes ◽  
Non Coding Rnas ◽  
Species Specific

Chronic metabolic disorders such as obesity and diabetes are associated with accelerated rates of macrovascular and microvascular complications, which are leading causes of morbidity and mortality worldwide. Further understanding of the underlying molecular mechanisms can aid in the development of novel drug targets and therapies to manage these disorders more effectively. Long non-coding RNAs (lncRNAs) that do not have protein-coding potential are expressed in a tissue- and species-specific manner and regulate diverse biological processes. LncRNAs regulate gene expression in cis or in trans through various mechanisms, including interaction with chromatin-modifying proteins and other regulatory proteins and via posttranscriptional mechanisms, including acting as microRNA sponges or as host genes of microRNAs. Emerging evidence suggests that major pathological factors associated with diabetes such as high glucose, free fatty acids, proinflammatory cytokines, and growth factors can dysregulate lncRNAs in inflammatory, cardiac, vascular, and renal cells leading to altered expression of key inflammatory genes and fibrotic genes associated with diabetic vascular complications. Here we review recent reports on lncRNA characterization, functions, and mechanisms of action in diabetic vascular complications and translational approaches to target them. These advances can provide new insights into the lncRNA-dependent actions and mechanisms underlying diabetic vascular complications and uncover novel lncRNA-based biomarkers and therapies to reduce disease burden and mortality.

scholarly journals A New Light on Potential Therapeutic Targets for Colorectal Cancer Treatment

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1438
Author(s):  
Wei-Lun Tsai ◽  
Chih-Yang Wang ◽  
Yu-Cheng Lee ◽  
Wan-Chun Tang ◽  
Gangga Anuraga ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Gene Expression Omnibus ◽  
Different Types ◽  
Geo Dataset ◽  
Non Coding Rnas ◽  
Poor Outcomes ◽  
Upregulated Genes

The development and progression of colorectal cancer (CRC) involve changes in genetic and epigenetic levels of oncogenes and/or tumor suppressors. In spite of advances in understanding of the molecular mechanisms involved in CRC, the overall survival rate of CRC still remains relatively low. Thus, more research is needed to discover and investigate effective biomarkers and targets for diagnosing and treating CRC. The roles of long non-coding RNAs (lncRNAs) participating in various aspects of cell biology have been investigated and potentially contribute to tumor development. Our recent study also showed that CRNDE was among the top 20 upregulated genes in CRC clinical tissues compared to normal colorectal tissues by analyzing a Gene Expression Omnibus (GEO) dataset (GSE21815). Although CRNDE is widely reported to be associated with different types of cancer, most studies of CRNDE were limited to examining regulation of its transcription levels, and in-depth mechanistic research is lacking. In the present study, CRNDE was found to be significantly upregulated in CRC patients at an advanced TNM stage, and its high expression was correlated with poor outcomes of CRC patients. In addition, we found that knocking down CRNDE could reduce lipid accumulation through the miR-29b-3p/ANGPTL4 axis and consequently induce autophagy of CRC cells.

scholarly journals Circular RNAs and Hepatocellular Carcinoma: New Epigenetic Players With Diagnostic and Prognostic Roles

2021 ◽  
Vol 11 ◽  
Author(s):  
Kedeerya Aishanjiang ◽  
Xin-dong Wei ◽  
Yi Fu ◽  
Xinjie Lin ◽  
Yujie Ma ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Hepatocellular Carcinoma ◽  
Closed Loop ◽  
Therapeutic Potential ◽  
Therapeutic Targets ◽  
Circular Rnas ◽  
Diagnosis And Prognosis ◽  
Physiological Processes ◽  
Non Coding Rnas ◽  
Novel Targets

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Due to the lack of potent diagnosis and prognosis biomarkers and effective therapeutic targets, the overall prognosis of survival is poor in HCC patients. Circular RNAs (circRNAs) are a class of novel endogenous non-coding RNAs with covalently closed loop structures and implicated in diverse physiological processes and pathological diseases. Recent studies have demonstrated the involvement of circRNAs in HCC diagnosis, prognosis, development, and drug resistance, suggesting that circRNAs may be a class of novel targets for improving HCC diagnosis, prognosis, and treatments. In fact, some artificial circRNAs have been engineered and showed their therapeutic potential in treating HCV infection and gastric cancer. In this review, we introduce the potential of circRNAs as biomarkers for HCC diagnosis and prognosis, as therapeutic targets for HCC treatments and discuss the challenges in circRNA research and chances of circRNA application.

scholarly journals Non-Coding RNAs in Pancreatic Cancer Diagnostics and Therapy: Focus on lncRNAs, circRNAs, and piRNAs

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4161
Author(s):  
Yiwei Li ◽  
Mohammed Najeeb Al Hallak ◽  
Philip A. Philip ◽  
Asfar S. Azmi ◽  
Ramzi M. Mohammad
Keyword(s):  
Pancreatic Cancer ◽  
High Mortality ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Cancer Diagnostics ◽  
Circular Rnas ◽  
Diagnosis And Prognosis ◽  
Cellular Signal ◽  
Non Coding Rnas

Pancreatic cancer is an aggressive malignance with high mortality. The lack of early diagnosis and effective therapy contributes to the high mortality of this deadly disease. For a long time being, the alterations in coding RNAs have been considered as major targets for diagnosis and treatment of pancreatic cancer. However, with the advances in high-throughput next generation of sequencing more alterations in non-coding RNAs (ncRNAs) have been discovered in different cancers. Further mechanistic studies have demonstrated that ncRNAs such as long noncoding RNAs (lncRNA), circular RNAs (circRNA) and piwi-interacting RNA (piRNA) play vital roles in the regulation of tumorigenesis, tumor progression and prognosis. In recent years, increasing studies have focused on the roles of ncRNAs in the development and progression of pancreatic cancer. Novel findings have demonstrated that lncRNA, circRNA, and piRNA are critically involved in the regulation of gene expression and cellular signal transduction in pancreatic cancer. In this review, we summarize the current knowledge of roles of lncRNA, circRNA, and piRNA in the diagnosis and prognosis of pancreatic cancer, and molecular mechanisms underlying the regulation of these ncRNAs and related signaling in pancreatic cancer therapy. The information provided here will help to find new strategies for better treatment of pancreatic cancer.

scholarly journals Functional Screening Techniques to Identify Long Non-Coding RNAs as Therapeutic Targets in Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3695
Author(s):  
Kathleen M. Lucere ◽  
Megan M. R. O’Malley ◽  
Sarah D. Diermeier
Keyword(s):  
Antisense Oligonucleotides ◽  
High Throughput Screening ◽  
Large Scale ◽  
Therapeutic Targets ◽  
Functional Screening ◽  
Protein Coding ◽  
Non Coding Rnas ◽  
New Therapeutic Targets ◽  
Functional Screens ◽  
Screening Approaches

Recent technological advancements such as CRISPR/Cas-based systems enable multiplexed, high-throughput screening for new therapeutic targets in cancer. While numerous functional screens have been performed on protein-coding genes to date, long non-coding RNAs (lncRNAs) represent an emerging class of potential oncogenes and tumor suppressors, with only a handful of large-scale screens performed thus far. Here, we review in detail currently available screening approaches to identify new lncRNA drivers of tumorigenesis and tumor progression. We discuss the various approaches of genomic and transcriptional targeting using CRISPR/Cas9, as well as methods to post-transcriptionally target lncRNAs via RNA interference (RNAi), antisense oligonucleotides (ASOs) and CRISPR/Cas13. We discuss potential advantages, caveats and future applications of each method to provide an overview and guide on investigating lncRNAs as new therapeutic targets in cancer.

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