scholarly journals Molecular Mechanisms of lncRNAs in the Dependent Regulation of Cancer and Their Potential Therapeutic Use

2022 ◽  
Vol 23 (2) ◽  
pp. 764
Author(s):  
Carlos García-Padilla ◽  
Ángel Dueñas ◽  
Virginio García-López ◽  
Amelia Aránega ◽  
Diego Franco ◽  
...  

Deep whole genome and transcriptome sequencing have highlighted the importance of an emerging class of non-coding RNA longer than 200 nucleotides (i.e., long non-coding RNAs (lncRNAs)) that are involved in multiple cellular processes such as cell differentiation, embryonic development, and tissue homeostasis. Cancer is a prime example derived from a loss of homeostasis, primarily caused by genetic alterations both in the genomic and epigenetic landscape, which results in deregulation of the gene networks. Deregulation of the expression of many lncRNAs in samples, tissues or patients has been pointed out as a molecular regulator in carcinogenesis, with them acting as oncogenes or tumor suppressor genes. Herein, we summarize the distinct molecular regulatory mechanisms described in literature in which lncRNAs modulate carcinogenesis, emphasizing epigenetic and genetic alterations in particular. Furthermore, we also reviewed the current strategies used to block lncRNA oncogenic functions and their usefulness as potential therapeutic targets in several carcinomas.

Author(s):  
Xuhui Chen ◽  
Kai Liu ◽  
Wen Xu ◽  
Gang Zhou ◽  
Chengfu Yuan

Background: Long non-coding RNA rhabdomyosarcoma 2-associated transcript (LncRNA RMST) will affect every aspect of tumor progression, such as proliferation, translocation and apoptosis. As a result, RMST can be used as an attractive biomarker for early diagnosis and clinical therapies of different disease states. This article aims to review pathophysiological functions, molecular mechanisms as well as promising biotherapies of RMST in multiple tumors. Methods: Through the systematic induction and summary of 46 papers published in PubMed concerning this study, the molecular mechanisms of RMST in all kinds of tumors have been reviewed. Results: LncRNA RMST is a tumor-related regulatory mediator, aberrantly expressed in diverse tumors, regarding medullary thyroid cancer, hepatocellular carcinoma, endometrial carcinoma, colon cancer, pancreatic cancer, glioma, Wilm’s tumor and breast cancer. Furthermore, as a mechanism-based player, RMST probably guides the translation and post-translation modification, containing DNA methylation and SUMOylation. It is capable of regulating distinct tumor cells and stem cells of biological behaviors via various molecular pathways. Conclusion: LncRNA RMST, potentially as an original therapeutic target, is valuable in the occurrence, development and apoptosis of different tumors.


Author(s):  
Jinliang Huang ◽  
Sipeng Wu ◽  
Pengcheng Wang ◽  
Geng Wang

Mitochondria are the main hubs for cellular energy production. Metabolites produced in mitochondria not only feed many important biosynthesis pathways but also function as signaling molecules. Mitochondrial biosynthesis requires collaboration of both nuclear and mitochondrial gene expression systems. In addition, mitochondria have to quickly respond to changes inside and outside the cells and have their own functional states reported to the nucleus and other cellular compartments. The underlying molecular mechanisms of these complex regulations have not been well understood. Recent evidence indicates that in addition to small molecules, non-coding RNAs may contribute to the communication between mitochondria and other cellular compartments and may even serve as signals. In this review, we summarize the current knowledge about mitochondrial non-coding RNAs (including nucleus-encoded non-coding RNAs that are imported into mitochondria and mitochondrion-encoded non-coding RNAs that are exported), their trafficking and their functions in co-regulation of mitochondrial and other cellular processes.


2021 ◽  
Vol 11 (6) ◽  
pp. 513
Author(s):  
Zheng Zhang ◽  
Meng Gu ◽  
Zhongze Gu ◽  
Yan-Ru Lou

Genetic polymorphisms are defined as the presence of two or more different alleles in the same locus, with a frequency higher than 1% in the population. Since the discovery of long non-coding RNAs (lncRNAs), which refer to a non-coding RNA with a length of more than 200 nucleotides, their biological roles have been increasingly revealed in recent years. They regulate many cellular processes, from pluripotency to cancer. Interestingly, abnormal expression or dysfunction of lncRNAs is closely related to the occurrence of human diseases, including cancer and degenerative neurological diseases. Particularly, their polymorphisms have been found to be associated with altered drug response and/or drug toxicity in cancer treatment. However, molecular mechanisms are not yet fully elucidated, which are expected to be discovered by detailed studies of RNA–protein, RNA–DNA, and RNA–lipid interactions. In conclusion, lncRNAs polymorphisms may become biomarkers for predicting the response to chemotherapy in cancer patients. Here we review and discuss how gene polymorphisms of lncRNAs affect cancer chemotherapeutic response. This knowledge may pave the way to personalized oncology treatments.


2021 ◽  
Vol 27 ◽  
Author(s):  
Wen Xu ◽  
Bei Wang ◽  
Yuxuan Cai ◽  
Jinlan Chen ◽  
Xing Lv ◽  
...  

Background: Long non-coding RNAs (lncRNA) have been identified as novel molecular regulators in cancers. LncRNA ADAMTS9-AS2 can mediate the occurrence and development of cancer through various ways such as regulating miRNAs, activating the classical signaling pathways in cancer, and so on, which have been studied by many scholars. In this review, we summarize the molecular mechanisms of ADAMTS9-AS2 in different human cancers. Methods: Through a systematic search of PubMed, lncRNA ADAMTS9-AS2 mediated molecular mechanisms in cancer are summarized inductively. Results: ADAMTS9-AS2 aberrantly expression in different cancers is closely related to cancer proliferation, invasion, migration, inhibition of apoptosis. The involvement of ADAMTS9-AS2 in DNA methylation, mediating PI3K / Akt / mTOR signaling pathways, regulating miRNAs and proteins, and such shows its significant potential as a therapeutic cancer target. Conclusion: LncRNA ADAMTS9-AS2 can become a promising biomolecular marker and a therapeutic target for human cancer.


Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5944
Author(s):  
Jianfei Tang ◽  
Xiaodan Fang ◽  
Juan Chen ◽  
Haixia Zhang ◽  
Zhangui Tang

Oral squamous cell carcinoma (OSCC) is a type of malignancy with high mortality, leading to poor prognosis worldwide. However, the molecular mechanisms underlying OSCC carcinogenesis have not been fully understood. Recently, the discovery and characterization of long non-coding RNAs (lncRNAs) have revealed their regulatory importance in OSCC. Abnormal expression of lncRNAs has been broadly implicated in the initiation and progress of tumors. In this review, we summarize the functions and molecular mechanisms regarding these lncRNAs in OSCC. In addition, we highlight the crosstalk between lncRNA and tumor microenvironment (TME), and discuss the potential applications of lncRNAs as diagnostic and prognostic tools and therapeutic targets in OSCC. Notably, we also discuss lncRNA-targeted therapeutic techniques including CRISPR-Cas9 as well as immune checkpoint therapies to target lncRNA and the PD-1/PD-L1 axis. Therefore, this review presents the future perspectives of lncRNAs in OSCC therapy, but more research is needed to allow the applications of these findings to the clinic.


Author(s):  
Hongying Zhao ◽  
Jian Shi ◽  
Yunpeng Zhang ◽  
Aimin Xie ◽  
Lei Yu ◽  
...  

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.


2019 ◽  
Vol 21 (1) ◽  
pp. 28 ◽  
Author(s):  
Silvia Ferrari ◽  
Maurizio Pesce

The heart is par excellence the ‘in-motion’ organ in the human body. Compelling evidence shows that, besides generating forces to ensure continuous blood supply (e.g., myocardial contractility) or withstanding passive forces generated by flow (e.g., shear stress on endocardium, myocardial wall strain, and compression strain at the level of cardiac valves), cells resident in the heart respond to mechanical cues with the activation of mechanically dependent molecular pathways. Cardiac stromal cells, most commonly named cardiac fibroblasts, are central in the pathologic evolution of the cardiovascular system. In their normal function, these cells translate mechanical cues into signals that are necessary to renew the tissues, e.g., by continuously rebuilding the extracellular matrix being subjected to mechanical stress. In the presence of tissue insults (e.g., ischemia), inflammatory cues, or modifiable/unmodifiable risk conditions, these mechanical signals may be ‘misinterpreted’ by cardiac fibroblasts, giving rise to pathology programming. In fact, these cells are subject to changing their phenotype from that of matrix renewing to that of matrix scarring cells—the so-called myo-fibroblasts—involved in cardiac fibrosis. The links between alterations in the abilities of cardiac fibroblasts to ‘sense’ mechanical cues and molecular pathology programming are still under investigation. On the other hand, various evidence suggests that cell mechanics may control stromal cells phenotype by modifying the epigenetic landscape, and this involves specific non-coding RNAs. In the present contribution, we will provide examples in support of this more integrated vision of cardiac fibrotic progression based on the decryption of mechanical cues in the context of epigenetic and non-coding RNA biology.


2020 ◽  
Author(s):  
xuanjun liu ◽  
Lan Yan ◽  
Chun Lin ◽  
Yiliang Zhang ◽  
Haofei Miao ◽  
...  

Abstract BackgroundDepression is one of the most common psychiatric disease worldwide. Although the research about the pathogenesis of depression have achieved progress, the detailed effect of non-coding RNAs (ncRNAs) in depression are still not clearly elucidated. This study was aimed to identify non-coding RNA biomarkers in stress-induced depression via comprehensive analysis of competing endogenous RNA networkMethodsIn this present study, we acquired RNA expression from RNA seq expression profile in three mice with depressive-like behaviors using chronic restraint stress paradigm and three C57BL/6J wild-type mice as control mice. ResultsA total of 41 differentially expressed circular RNAs (circRNAs) and 181 differentially expressed messenger RNAs (mRNAs) were up-regulated, and 65 differentially expressed circRNAs and 289 differentially expressed mRNAs were down-regulated, which were selected by a threshold of fold change ≥2 and a p-value < 0.05. Gene Ontology was performed to analyze the biological functions, and we predicted potential signaling pathways based on Kyoto Encyclopedia of Genes and Genomes pathway database. In addition, we constructed a circRNA-microRNA (miRNA)-mRNA regulatory network to further identify non-coding RNAs biomarkers. ConclusionsOur findings provide a promising perspective for further research into molecular mechanisms of depression, and targeting circRNA -mediated competing endogenous RNA (ceRNA) network is a useful strategy to early recognize the depression.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Sung-Hyun Kim ◽  
Key-Hwan Lim ◽  
Sumin Yang ◽  
Jae-Yeol Joo

AbstractBrain tumors are associated with adverse outcomes despite improvements in radiation therapy, chemotherapy, and photodynamic therapy. However, treatment approaches are evolving, and new biological phenomena are being explored to identify the appropriate treatment of brain tumors. Long non-coding RNAs (lncRNAs), a type of non-coding RNA longer than 200 nucleotides, regulate gene expression at the transcriptional, post-transcriptional, and epigenetic levels and are involved in a variety of biological functions. Recent studies on lncRNAs have revealed their aberrant expression in various cancers, with distinct expression patterns associated with their instrumental roles in cancer. Abnormal expression of lncRNAs has also been identified in brain tumors. Here, we review the potential roles of lncRNAs and their biological functions in the context of brain tumors. We also summarize the current understanding of the molecular mechanisms and signaling pathways related to lncRNAs that may guide clinical trials for brain tumor therapy.


2021 ◽  
Vol 22 (16) ◽  
pp. 8527
Author(s):  
Leila Jahangiri ◽  
Perla Pucci ◽  
Tala Ishola ◽  
Ricky M. Trigg ◽  
John A. Williams ◽  
...  

MYC is a target of the Wnt signalling pathway and governs numerous cellular and developmental programmes hijacked in cancers. The amplification of MYC is a frequently occurring genetic alteration in cancer genomes, and this transcription factor is implicated in metabolic reprogramming, cell death, and angiogenesis in cancers. In this review, we analyse MYC gene networks in solid cancers. We investigate the interaction of MYC with long non-coding RNAs (lncRNAs). Furthermore, we investigate the role of MYC regulatory networks in inducing changes to cellular processes, including autophagy and mitophagy. Finally, we review the interaction and mutual regulation between MYC and lncRNAs, and autophagic processes and analyse these networks as unexplored areas of targeting and manipulation for therapeutic gain in MYC-driven malignancies.


Sign in / Sign up

Export Citation Format

Share Document