Non-coding RNAs In Lung Cancer Research Articles

Non-coding RNAs and exosomal non-coding RNAs in lung cancer: insights into their functions.

Lung cancer is the second most common form of cancer worldwide Research points to the pivotal role of non-coding RNAs (ncRNAs) in controlling and managing the pathology by controlling essential pathways. ncRNAs have all been identified as being either up- or downregulated among individuals suffering from lung cancer thus hinting that they may play a role in either promoting or suppressing the spread of the disease. Several ncRNAs could be effective non-invasive biomarkers to diagnose or even serve as effective treatment options for those with lung cancer, and several molecules have emerged as potential targets of interest. Given that ncRNAs are contained in exosomes and are implicated in the development and progression of the malady. Herein, we have summarized the role of ncRNAs in lung cancer. Moreover, we highlight the role of exosomal ncRNAs in lung cancer.

Non-coding RNAs in lung cancer: molecular mechanisms and clinical applications.

Lung cancer (LC) is a heterogeneous disease with high malignant degree, rapid growth, and early metastasis. The clinical outcomes of LC patients are generally poor due to the insufficient elucidation of pathological mechanisms, low efficiency of detection and assessment methods, and lack of individualized therapeutic strategies. Non-coding RNAs (ncRNAs), including microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA), are endogenous regulators that are widely involved in the modulation of almost all aspects of life activities, from organogenesis and aging to immunity and cancer. They commonly play vital roles in various biological processes by regulating gene expression via their interactions with DNA, RNA, or protein. An increasing amount of studies have demonstrated that ncRNAs are closely correlated with the initiation and development of LC. Their dysregulation promotes the progression of LC via distinct mechanisms, such as influencing protein activity, activating oncogenic signaling pathways, or altering specific gene expression. Furthermore, some ncRNAs present certain clinical values as biomarker candidates and therapeutic targets for LC patients. A complete understanding of their mechanisms in LC progression may be highly beneficial to developing ncRNA-based therapeutics for LC patients. This review mainly focuses on the intricate mechanisms of miRNA, lncRNA, and circRNA involved in LC progression and discuss their underlying applications in LC treatment.

Extracellular Vesicle (EVs) Associated Non-Coding RNAs in Lung Cancer and Therapeutics.

Lung cancer is one of the most lethal forms of cancer, with a very high mortality rate. The precise pathophysiology of lung cancer is not well understood, and pertinent information regarding the initiation and progression of lung cancer is currently a crucial area of scientific investigation. Enhanced knowledge about the disease will lead to the development of potent therapeutic interventions. Extracellular vesicles (EVs) are membrane-bound heterogeneous populations of cellular entities that are abundantly produced by all cells in the human body, including the tumor cells. A defined class of EVs called small Extracellular Vesicles (sEVs or exosomes) carries key biomolecules such as RNA, DNA, Proteins and Lipids. Exosomes, therefore, mediate physiological activities and intracellular communication between various cells, including constituent cells of the tumor microenvironment, namely stromal cells, immunological cells, and tumor cells. In recent years, a surge in studying tumor-associated non-coding RNAs (ncRNAs) has been observed. Subsequently, studies have also reported that exosomes abundantly carry different species of ncRNAs and these exosomal ncRNAs are functionally involved in cancer initiation and progression. Here, we discuss the function of exosomal ncRNAs, such as miRNAs and long non-coding RNAs, in the pathophysiology of lung tumors. Further, the future application of exosomal-ncRNAs in clinics as biomarkers and therapeutic targets in lung cancer is also discussed due to the multifaceted influence of exosomes on cellular physiology.

Identification of metastasis-related long non-coding RNAs in lung cancer through a novel tumor mesenchymal score

Long non-coding RNAs (lncRNAs) have been proven to play critical roles in epithelial-mesenchymal transition (EMT) and metastasis of lung cancer. However, the biological functions and related mechanisms of lncRNAs are unclear. In addition, the EMT-based prognosis prediction in lung cancer still lacks investigation. Here, we established the methodology of identifying critical metastasis-related lncRNAs using comprehensive datasets of cancer transcriptome, genome and epigenome, and also provided tools for prognosis prediction in lung cancer. Initially, important mesenchymal marker genes were identified to compose the tumor mesenchymal score, which predicted patient prognosis in lung cancer, especially lung adenocarcinoma (LUAD). The score was also correlated with several crucial biological and physiological processes, such as tumor immune and hypoxia. Based on the score, lung cancer patients was classified into epithelial and mesenchymal subtypes, and lncRNAs which exhibited expressional dysregulation, promotor methylation alteration and copy number variation between the two subtypes in LUAD were identified and underwent further prognostic analyses. Finally, we identified 14 lncRNAs as EMT-related and significant biomarkers in prognosis prediction of LUAD. As validation, lncRNA RBPMS-AS1 was proven to be co-expressed with epithelial biomarkers, suppressive for A549 cell migration, invasion and EMT, and also significantly associated with better outcomes of LUAD patients, suggesting the potential of RBPMS-AS1 to serve as a lncRNA epithelial biomarker in metastasis of LUAD. Based on the identified lncRNAs, an EMT-linked lncRNA prognostic signature was further established. Taken together, our study provides robust predictive tools, potential lncRNA targets and feasible screening strategies for future study of lung cancer metastasis.

Long Noncoding RNAs in Lung Cancer: From Disease Markers to Treatment Roles.

There is an urgent need to identify reliable biomarkers that can be used in early diagnosis, prognostication prediction and as possible therapeutic targets for lung cancer due to its current poor prognosis. Long noncoding RNAs (lncRNAs) have recently attracted additional attention due to their potential role in carcinogenesis, invasion and metastasis. Issues involved in the biofunctions and regulatory mechanisms of oncogenic and tumor-suppressive lncRNAs in lung cancer are discussed. Some lncRNAs have shown good diagnostic value, especially in combination with conventional serum protein markers. The use of antisense oligonucleotides, small molecules and RNA interference techniques have shown promise as direct therapeutic tools for targeting lncRNAs in preclinical studies. The biomarker function of lncRNAs may also indirectly involved in tumor therapy as a reference to conventional therapy. Overall, the concept of using lncRNAs as biomarkers for prognostication and intervention in lung cancer is still in its infancy, and only with more in-depth studies could they have a significant impact.

Emerging role of exosomal long non-coding RNAs in lung cancer.

Lung cancer is one of the most common malignancies worldwide. Also, it is the leading cause of cancer morbidity and mortality in men. Despite advances in lung cancer diagnosis and treatment, novel approaches are strongly needed to promote early diagnosis and effective treatment of lung cancer. Presently, accumulating data reveal that long noncoding RNAs (lncRNAs) are differentially enriched in exosomes and mediate multiple biological processes in lung cancer, suggesting the potential application of exosomal lncRNAs as diagnostic biomarkers and therapeutic targets. In this review, we described the emerging roles of lncRNAs specifically sorted into exosomes in lung cancer. We discussed the current knowledge of the exosomal lncRNA sorting mechanism and highlighted opportunities for exosome-derived lncRNAs as biomarkers in clinical practice. In particular, we systematically summarized the biological functions of exosomal lncRNAs in lung cancer.

Long Non-Coding RNAs in Lung Cancer: The Role in Tumor Microenvironment.

The development of various therapeutic interventions, particularly immune checkpoint inhibitor therapy, have effectively induced tumor remission for patients with advanced lung cancer. However, few cancer patients can obtain significant and long-lasting therapeutic effects for the limitation of immunological nonresponse and resistance. For this case, it’s urgent to identify new biomarkers and develop therapeutic targets for future immunotherapy. Over the past decades, tumor microenvironment (TME)-related long non-coding RNAs (lncRNAs) have gradually become well known to us. A large number of existing studies have indicated that TME-related lncRNAs are one of the major factors to realize precise diagnosis and treatment of lung cancer. Herein, this paper discusses the roles of lncRNAs in TME, and the potential application of lncRNAs as biomarkers or therapeutic targets for immunotherapy in lung cancer.

The roles of long non-coding RNAs in lung cancer.

Lung cancer is the most common malignancy, being a serious threat of human lives. The incidence and mortality of lung cancer has been increasing rapidly in the past decades. Although the development of new therapeutic modes, such as target therapy, the overall survival rate of lung cancer remains low. It is urgent to advance the understanding of molecular oncology and find novel biomarkers and targets for the early diagnosis, treatment, and prognostic prediction of lung cancer. Long non-coding RNAs (lncRNAs) are non-protein coding RNA transcripts that are more than 200 nucleotides in length. LncRNAs exert diverse biological functions by regulating gene expressions at transcriptional, translational, and post-translational levels. In the past decade, it has been shown that lncRNAs are extensively involved in the pathogenesis of various diseases, including lung cancer. In this review, we highlighted the lncRNAs characterized in lung cancer and discussed their translational potential in lung cancer clinics.

New Insights into the Importance of Long Non-Coding RNAs in Lung Cancer: Future Clinical Approaches.

In mammals, a large part of the gene expression products come from the non-coding ribonucleotide sequences of the protein. These short and long sequences are within the range of tens to hundreds of nucleotides, encompassing more than 200 RNA molecules, and their function is known as the molecular structure of long non-coding RNA (lncRNA). LncRNA molecules are unique nucleotides that have a substantial role in epigenetic regulation, transcription, and post-transcriptional modifications in different ways. According to the results of recent studies, lncRNAs have been shown to assume various roles, including tumor suppression or oncogenic functions in common types of cancer such as lung and breast cancer. These non-coding RNAs (ncRNAs) play a pivotal role in activating transcription factors, managing the ribonucleoproteins, the framework for collecting co-proteins, intermittent processing regulations, chromatin status alterations, and maintaining the control within the cell. Cutting-edge technologies have been introduced to disclose several types of lncRNAs within the nucleus and the cytoplasm, which have accomplished important achievements that are applicable in medicine. Due to these efforts, various data centers have been created to facilitate and modify scientific information related to these molecules, including detection, classification, biological evolution, gene status, spatial structure, status, and location of these small molecules. In the present study, we attempt to present the impacts of these ncRNAs on lung cancer with an emphasis on their mechanisms and functions.

Emerging role of HOX genes and their related long noncoding RNAs in lung cancer.

The transcription factor homeobox (Hox) proteins are the master regulator for the embryonic development. Studies have identified new functions for HOX in the regulation of metabolism and other primary cellular processes in humans. Their dysregulation has been observed in a variety of cancers and accumulating evidence has revealed the crucial role of HOX in cancer progression, metastasis, and resistance to therapy. HOX-related long non-coding RNAs (lncRNAs) became the most attracting lncRNAs recently that play critical role in gene regulation and chromatin dynamics in cancers. In this review, we explore the roles of HOX and their related lncRNAs in lung cancer, indicating HOX genes as potential therapeutic targets in lung cancer.

Multidimensional communication of microRNAs and long non-coding RNAs in lung cancer.

Non-coding RNAs (ncRNAs) have been a hot topic for many years in the field of cancer research,especially miRNAs and lncRNAs. Because they play critical roles in regulating various cellular processes and are more often involved in tumorigenesis than protein-coding genes. But the cross talk between miRNAs and lncRNAs in cancer has been scarcely studied. This articleaims to provide a retrospective review of the latest research on the link between miRNAs and lncRNAs in lung cancer and discusses their potential role as diagnostic biomarkers and therapeutic targets for lung cancer in clinical practice. We reviewed literatures about ncRNAs and lung cancer from PUBMED databases in this article. As shown in our review, miRNAs and lncRNAs could represent underlying targets for diagnosis, therapy, prognosis, and drug resistence of lung cancer. By acting as ceRNAs, lncRNAs can competitively inhibit the expression levels of miRNAs, and the lncRNA/miRNA axis can contribute to tumorigenesis, metastasis, and mutidrug resistance in lung cancer via various classic signaling pathways or related proteins. Based on present knowledge, ncRNAs may provide a novel perspectiveto understand the pathogenesis of lung cancer and could be candidates in screening of therapeutic targets for lung cancer.

Identification and Characterization of TGF‐beta induced Long Noncoding RNAs in Lung Cancer

Lung cancer is the most lethal cancer worldwide due to high ratio of recurrence and high probability to undergo metastasis. As Epithelial‐mesenchymal transition (EMT) plays a major role during metastasis, how EMT is regulated by periphery in the lung cancer is particularly important. Although initiation of EMT can be triggered by TGF‐beta found to be overexpressed in lung cancer, how EMT can be affected by TGF‐beta signaling in different disease stages and its contribution to the heterogenecity of tumor cells are still unclear. This hampers our ability to effectively treat and block metastasis in lung cancer. Recently, long noncoding RNAs have emerged as a new player for tumor metastasis. We therefore hypothesize that lncRNAs mediated TGF‐beta signaling might be involved during EMT in lung cancer. Using RNA‐seq, we identified changes in lncRNAs profiles during different time points after TGF‐beta treatment in A549 cells. Early responded lncRNAs are major regulators in signaling and will be selected as primary candidates for further study. Expression patterns will be re‐validated by other lung cancer cell line with TGF‐beta treatment. The lncRNA candidates that have altered expression levels in response to TGF‐beta will be chosen to determine their effects on migration and gene regulation using wound healing and expression microarray. In situ hybridization will eventually be carried out to correlate the expression level of lncRNA in lung cancer clinical samples and re‐probe with EMT markers. The regulation of lncRNA in EMT would be validated with lncRNA knockout with TGF‐beta stimulation in A549 cells. The abilities of migration and invasion in knockout cells would be determined in vivo. In the end, we found the candidate lncRNA play a critical role in EMT with TGF‐beta stimulation in lung cancer.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Functions and mechanisms of long noncoding RNAs in lung cancer.

Lung cancer is a heterogeneous disease, and there is a lack of adequate biomarkers for diagnosis. Long noncoding RNAs (lncRNAs) are emerging as an important set of molecules because of their roles in various key pathophysiological pathways, including cell growth, apoptosis, and metastasis. We review the current knowledge of the lncRNAs in lung cancer. In-depth analyses of lncRNAs in lung cancer have increased the number of potential effective biomarkers, thus providing options to increase the therapeutic benefit. In this review, we summarize the functions, mechanisms, and regulatory networks of lncRNAs in lung cancer, providing a basis for further research in this field.

Abstract IA08: Functional long noncoding RNAs in lung cancer

Abstract The majority of the human genome is transcribed into non-protein-coding RNA. Hence, RNA is also the primary product of the cancer genome. We have defined the ncRNA expression landscape of lung, breast and liver cancer providing a comprehensive expression map of over 17000 long ncRNAs and discovering new lncRNAs associated with cancer whose molecular and cellular functions we are currently elucidating exploiting our custom siRNA library targeting 638 tumor-associated lncRNAs. The nuclear lncRNA MALAT1 was one of the first lncRNAs associated with cancer: it is associated with metastasis development in lung cancer. However, its high abundance and nuclear localization have hampered its functional analysis. To uncover its functional importance, we developed a MALAT1 knockout model in human lung tumor cells by genomically integrating RNA destabilizing elements site-specifically into the MALAT1 locus. This approach yielded a 1000-fold silencing of MALAT1 providing a unique loss-of-function model. Proposed mechanisms of MALAT1 action include regulation of splicing or gene expression. In lung cancer, MALAT1 does not alter alternative splicing but regulates gene expression inducing a signature of metastasis-associated genes. Consequently, MALAT1-deficient cells are impaired in migration and form fewer tumor nodules in a mouse xenograft model. Encouraged by this discovery of the essential function of MALAT1 in lung cancer metastasis, we analyzed whether MALAT1 could serve as therapeutic target for an Antisense oligonucleotide (ASO). Notably, MALAT1-ASO treatment prevented metastasis formation after tumor implantation. Thus, targeting MALAT1 with ASOs provided a therapeutic approach to prevent lung cancer metastasis with MALAT1 serving as both, predictive marker and therapeutic target. In summary, ten years after the discovery of the lncRNA MALAT1 as a biomarker for lung cancer metastasis, our loss-of-function model unraveled the active function of MALAT1 as a regulator of gene expression governing hallmarks of lung cancer metastasis. Citation Format: Sven Diederichs. Functional long noncoding RNAs in lung cancer. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr IA08.

Long noncoding RNAs in lung cancer: what we know in 2015.

Lung cancer ranks as the first most common cancer and the first leading cause of cancer-related death in China and worldwide. Due to the difficulty in early diagnosis and the onset of cancer metastasis, the 5-year survival rate of lung cancer remains extremely low. Long noncoding RNAs (lncRNAs), which lacking protein-coding ability, have recently emerged as pivotal participants in biological processes, often dysregulated in a range of cancers, including lung cancer. In this review, we highlight the recent findings of lncRNAs in lung cancer pathogenesis. While our understanding of lncRNAs in the onset and progression of lung cancer is still in its infancy, there is no doubt that understanding the activities of lncRNAs will certainly secure strong biomarkers and improve treatment options for lung cancer patients.

Non-coding RNAs in lung cancer.

The discovery that protein-coding genes represent less than 2% of all human genome, and the evidence that more than 90% of it is actively transcribed, changed the classical point of view of the central dogma of molecular biology, which was always based on the assumption that RNA functions mainly as an intermediate bridge between DNA sequences and protein synthesis machinery. Accumulating data indicates that non-coding RNAs are involved in different physiological processes, providing for the maintenance of cellular homeostasis. They are important regulators of gene expression, cellular differentiation, proliferation, migration, apoptosis, and stem cell maintenance. Alterations and disruptions of their expression or activity have increasingly been associated with pathological changes of cancer cells, this evidence and the prospect of using these molecules as diagnostic markers and therapeutic targets, make currently non-coding RNAs among the most relevant molecules in cancer research. In this paper we will provide an overview of non-coding RNA function and disruption in lung cancer biology, also focusing on their potential as diagnostic, prognostic and predictive biomarkers.

Roles of long noncoding RNA in lung cancer

Long noncoding RNAs are a group of noncoding RNAs with a length more than 200 nucleotides. Recent studies have revealed that long noncoding RNAs play an important role in the development and progression of cancer. Lung cancer is the leading cause of cancer-related death all over the world. In this article, we review the roles of long noncoding RNAs in lung cancer to provide new insights into the diagnosis and treatment of the disease.

Transcriptome sequencing reveals altered long intergenic non-coding RNAs in lung cancer.

BackgroundLong intergenic non-coding RNAs (lncRNAs) represent an emerging and under-studied class of transcripts that play a significant role in human cancers. Due to the tissue- and cancer-specific expression patterns observed for many lncRNAs it is believed that they could serve as ideal diagnostic biomarkers. However, until each tumor type is examined more closely, many of these lncRNAs will remain elusive.ResultsHere we characterize the lncRNA landscape in lung cancer using publicly available transcriptome sequencing data from a cohort of 567 adenocarcinoma and squamous cell carcinoma tumors. Through this compendium we identify over 3,000 unannotated intergenic transcripts representing novel lncRNAs. Through comparison of both adenocarcinoma and squamous cell carcinomas with matched controls we discover 111 differentially expressed lncRNAs, which we term lung cancer-associated lncRNAs (LCALs). A pan-cancer analysis of 324 additional tumor and adjacent normal pairs enable us to identify a subset of lncRNAs that display enriched expression specific to lung cancer as well as a subset that appear to be broadly deregulated across human cancers. Integration of exome sequencing data reveals that expression levels of many LCALs have significant associations with the mutational status of key oncogenes in lung cancer. Functional validation, using both knockdown and overexpression, shows that the most differentially expressed lncRNA, LCAL1, plays a role in cellular proliferation.ConclusionsOur systematic characterization of publicly available transcriptome data provides the foundation for future efforts to understand the role of LCALs, develop novel biomarkers, and improve knowledge of lung tumor biology.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-014-0429-8) contains supplementary material, which is available to authorized users.

Transcriptome sequencing reveals altered long intergenic non-coding RNAs in lung cancer

BackgroundLong intergenic non-coding RNAs (lncRNAs) represent an emerging and under-studied class of transcripts that play a significant role in human cancers. Due to the tissue- and cancer-specific expression patterns observed for many lncRNAs it is believed that they could serve as ideal diagnostic biomarkers. However, until each tumor type is examined more closely, many of these lncRNAs will remain elusive.ResultsHere we characterize the lncRNA landscape in lung cancer using publicly available transcriptome sequencing data from a cohort of 567 adenocarcinoma and squamous cell carcinoma tumors. Through this compendium we identify over 3,000 unannotated intergenic transcripts representing novel lncRNAs. Through comparison of both adenocarcinoma and squamous cell carcinomas with matched controls we discover 111 differentially expressed lncRNAs, which we term lung cancer-associated lncRNAs (LCALs). A pan-cancer analysis of 324 additional tumor and adjacent normal pairs enable us to identify a subset of lncRNAs that display enriched expression specific to lung cancer as well as a subset that appear to be broadly deregulated across human cancers. Integration of exome sequencing data reveals that expression levels of many LCALs have significant associations with the mutational status of key oncogenes in lung cancer. Functional validation, using both knockdown and overexpression, shows that the most differentially expressed lncRNA, LCAL1, plays a role in cellular proliferation.ConclusionsOur systematic characterization of publicly available transcriptome data provides the foundation for future efforts to understand the role of LCALs, develop novel biomarkers, and improve knowledge of lung tumor biology.