scholarly journals Integrator restrains paraspeckles assembly by promoting isoform switching of the lncRNA NEAT1

2020 ◽  
Vol 6 (27) ◽  
pp. eaaz9072 ◽  
Author(s):  
Jasmine Barra ◽  
Gabriel S. Gaidosh ◽  
Ezra Blumenthal ◽  
Felipe Beckedorff ◽  
Mina M. Tayari ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Cancer Biology ◽  
Nuclear Bodies ◽  
Physiological Processes ◽  
Polyadenylated Rna ◽  
Non Coding Rna ◽  
Isoform Switching ◽  
Low Levels ◽  
Lncrna Neat1 ◽  
Long Non Coding Rna

RNA 3′ end processing provides a source of transcriptome diversification which affects various (patho)-physiological processes. A prime example is the transcript isoform switch that leads to the read-through expression of the long non-coding RNA NEAT1_2, at the expense of the shorter polyadenylated transcript NEAT1_1. NEAT1_2 is required for assembly of paraspeckles (PS), nuclear bodies that protect cancer cells from oncogene-induced replication stress and chemotherapy. Searching for proteins that modulate this event, we identified factors involved in the 3′ end processing of polyadenylated RNA and components of the Integrator complex. Perturbation experiments established that, by promoting the cleavage of NEAT1_2, Integrator forces NEAT1_2 to NEAT1_1 isoform switching and, thereby, restrains PS assembly. Consistently, low levels of Integrator subunits correlated with poorer prognosis of cancer patients exposed to chemotherapeutics. Our study establishes that Integrator regulates PS biogenesis and a link between Integrator, cancer biology, and chemosensitivity, which may be exploited therapeutically.

scholarly journals LncRNA NEAT1 in Paraspeckles: A Structural Scaffold for Cellular DNA Damage Response Systems?

2020 ◽  
Vol 6 (3) ◽  
pp. 26 ◽  
Author(s):  
Elisa Taiana ◽  
Domenica Ronchetti ◽  
Katia Todoerti ◽  
Lucia Nobili ◽  
Pierfrancesco Tassone ◽  
...  
Keyword(s):  
Dna Damage ◽  
Current Knowledge ◽  
Nuclear Bodies ◽  
Cellular Functions ◽  
Damage Repair ◽  
Non Coding Rna ◽  
Response Systems ◽  
Cellular Dna ◽  
Lncrna Neat1 ◽  
Long Non Coding Rna

Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA (lncRNA) reported to be frequently deregulated in various types of cancers and neurodegenerative processes. NEAT1 is an indispensable structural component of paraspeckles (PSs), which are dynamic and membraneless nuclear bodies that affect different cellular functions, including stress response. Furthermore, increasing evidence supports the crucial role of NEAT1 and essential structural proteins of PSs (PSPs) in the regulation of the DNA damage repair (DDR) system. This review aims to provide an overview of the current knowledge on the involvement of NEAT1 and PSPs in DDR, which might strengthen the rationale underlying future NEAT1-based therapeutic options in tumor and neurodegenerative diseases.

scholarly journals Long non-coding RNA AFAP1-AS1 accelerates lung cancer cells migration and invasion by interacting with SNIP1 to upregulate c-Myc

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Yu Zhong ◽  
Liting Yang ◽  
Fang Xiong ◽  
Yi He ◽  
Yanyan Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cancer Metastasis ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Lung Cancer Patients ◽  
Lung Cancer Metastasis ◽  
Non Coding Rna ◽  
Long Non Coding Rna

AbstractActin filament associated protein 1 antisense RNA 1 (named AFAP1-AS1) is a long non-coding RNA and overexpressed in many cancers. This study aimed to identify the role and mechanism of AFAP1-AS1 in lung cancer. The AFAP1-AS1 expression was firstly assessed in 187 paraffin-embedded lung cancer and 36 normal lung epithelial tissues by in situ hybridization. The migration and invasion abilities of AFAP1-AS1 were investigated in lung cancer cells. To uncover the molecular mechanism about AFAP1-AS1 function in lung cancer, we screened proteins that interact with AFAP1-AS1 by RNA pull down and the mass spectrometry analyses. AFAP1-AS1 was highly expressed in lung cancer clinical tissues and its expression was positively correlated with lung cancer patients’ poor prognosis. In vivo experiments confirmed that AFAP1-AS1 could promote lung cancer metastasis. AFAP1-AS1 promoted lung cancer cells migration and invasion through interacting with Smad nuclear interacting protein 1 (named SNIP1), which inhibited ubiquitination and degradation of c-Myc protein. Upregulation of c-Myc molecule in turn promoted the expression of ZEB1, ZEB2, and SNAIL gene, which ultimately enhanced epithelial to mesenchymal transition (EMT) and lung cancer metastasis. Understanding the molecular mechanism by which AFAP1-AS1 promotes lung cancer’s migration and invasion may provide novel therapeutic targets for lung cancer patients’ early diagnosis and therapy.

scholarly journals LncRNA NEAT1 Enhances Glioma Progression via Regulating the miR-128-3p/ITGA5 Axis

2021 ◽  
Author(s):  
Jiakai Chen ◽  
Handong Wang ◽  
Junjun Wang ◽  
Wenhao Niu ◽  
Chulei Deng ◽  
...  
Keyword(s):  
Flow Cytometric Analysis ◽  
Biological Functions ◽  
Quantitative Real Time Pcr ◽  
Flow Cytometric ◽  
Non Coding Rna ◽  
Rna Immunoprecipitation ◽  
Human Gbm ◽  
Novel Strategy ◽  
Lncrna Neat1 ◽  
Long Non Coding Rna

AbstractAccumulating evidences indicate that long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) promotes the progression of glioma. In this study, we postulated that NEAT1 may act as a miR-128-3p sponge. Relative levels of NEAT1 and miR-128-3p expression in human glioma samples and GBM cells were detected using quantitative real-time PCR. By means of CCK-8 assays, transwell assays, and flow cytometric analysis, the biological functions of miR-128-3p and NEAT1 were investigated in U87MG and U251MG human GBM cell lines with stable miR-128-3p and NEAT1 knockdown or overexpression. The luciferase reports, RNA pull-down assay, and RNA immunoprecipitation assay were conducted to determine the relevance of NEAT1 and miR-128-3p in glioma. As a result, high expression of NEAT1 and lack of miR-128-3p were observed in glioma specimens and cells. By binding to anti-oncogene miR-128-3p in the nucleus, NEAT1 enhanced tumorigenesis and glioma development. Further experiments suggested that ITGA5 expression was increased in glioma tissues and was found to be connected with miR-128-3p. Additionally, NEAT1 facilitated ITGA5 expression via competitively binding to miR-128-3p. For this reason, ITGA5 would not be decomposed by miR-128-3p and could activate FAK signaling pathway, thereby promoting cell growth. Collectively, these results indicated that the NEAT1/miR-128-3p/ITGA5 axis was involved in glioma initiation and progression, and might offer a potential novel strategy for treatment of glioma.

scholarly journals Meta-analysis of the prognostic value of long non-coding RNA PVT1 for cancer patients

Medicine ◽  
2018 ◽  
Vol 97 (49) ◽  
pp. e13548 ◽  
Author(s):  
Chao Ma ◽  
Xing-Guo Nie ◽  
Yan-Li Wang ◽  
Da-Peng Wu ◽  
Qiu-dong Liang
Keyword(s):  
Cancer Patients ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Non Coding Rna ◽  
Long Non Coding Rna

scholarly journals Identifying Structural Domains and Conserved Regions in the Long Non-Coding RNA lncTCF7

2019 ◽  
Vol 20 (19) ◽  
pp. 4770 ◽  
Author(s):  
Michael C. Owens ◽  
Sean C. Clark ◽  
Allison Yankey ◽  
Srinivas Somarowthu
Keyword(s):  
Structure Function ◽  
Cancer Biology ◽  
Structural Model ◽  
Structural Domains ◽  
Conserved Regions ◽  
Non Coding Rna ◽  
Function Relationship ◽  
Modular Domains ◽  
Relationship Of ◽  
Long Non Coding Rna

Long non-coding RNA (lncRNA) biology is a rapidly growing area of study. Thousands of lncRNAs are implicated as key players in cellular pathways and cancer biology. However, the structure–function relationships of these novel biomolecules are not well understood. Recent structural studies suggest that lncRNAs contain modular structural domains, which play a crucial role in their function. Here, we hypothesized that such structural domains exist in lncTCF7, a conserved lncRNA implicated in the development and progression of several cancers. To understand the structure–function relationship of lncTCF7, we characterized its secondary structure using chemical probing methods. Our model revealed structural domains and conserved regions in lncTCF7. One of the modular domains identified here coincides with a known protein-interacting domain. The model reported herein is, to our knowledge, the first structural model of lncTCF7 and thus will serve to direct future studies that will provide fundamental insights into the function of this lncRNA.

Extracellular vesicles: their role in cancer biology and epithelial–mesenchymal transition

2016 ◽  
Vol 474 (1) ◽  
pp. 21-45 ◽  
Author(s):  
Shashi K. Gopal ◽  
David W. Greening ◽  
Alin Rai ◽  
Maoshan Chen ◽  
Rong Xu ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Cancer Biology ◽  
Epithelial Mesenchymal Transition ◽  
Current Knowledge ◽  
Cell Communication ◽  
Metastatic Potential ◽  
Messenger Rnas ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Cell–cell communication is critical across an assortment of physiological and pathological processes. Extracellular vesicles (EVs) represent an integral facet of intercellular communication largely through the transfer of functional cargo such as proteins, messenger RNAs (mRNAs), microRNA (miRNAs), DNAs and lipids. EVs, especially exosomes and shed microvesicles, represent an important delivery medium in the tumour micro-environment through the reciprocal dissemination of signals between cancer and resident stromal cells to facilitate tumorigenesis and metastasis. An important step of the metastatic cascade is the reprogramming of cancer cells from an epithelial to mesenchymal phenotype (epithelial–mesenchymal transition, EMT), which is associated with increased aggressiveness, invasiveness and metastatic potential. There is now increasing evidence demonstrating that EVs released by cells undergoing EMT are reprogrammed (protein and RNA content) during this process. This review summarises current knowledge of EV-mediated functional transfer of proteins and RNA species (mRNA, miRNA, long non-coding RNA) between cells in cancer biology and the EMT process. An in-depth understanding of EVs associated with EMT, with emphasis on molecular composition (proteins and RNA species), will provide fundamental insights into cancer biology.

scholarly journals HOTAIR long non-coding RNA is a negative prognostic factor not only in primary tumors, but also in the blood of colorectal cancer patients

2014 ◽  
Vol 35 (7) ◽  
pp. 1510-1515 ◽  
Author(s):  
M. Svoboda ◽  
J. Slyskova ◽  
M. Schneiderova ◽  
P. Makovicky ◽  
L. Bielik ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Primary Tumors ◽  
Non Coding Rna ◽  
Negative Prognostic Factor ◽  
Colorectal Cancer Patients ◽  
Long Non Coding Rna

scholarly journals Long non-coding RNA XIST predicts worse prognosis in digestive system tumors: a systemic review and meta-analysis

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Xuefang Liu ◽  
Xinliang Ming ◽  
Wei Jing ◽  
Ping Luo ◽  
Nandi Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cancer Patients ◽  
Digestive System ◽  
Meta Analysis ◽  
Predictive Biomarker ◽  
Systemic Review ◽  
Cochrane Library ◽  
Expression Levels ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Increasing studies are indicating that long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is associated with the prognosis of cancer patients. However, the results have been disputed. Therefore, we aimed to further explore the prognostic value and clinical significance of XIST in various types of cancers. Then, we focussed our research on the comparison of the predictive value of XIST between digestive system tumors and non-digestive system tumors. We performed a systematic search by looking up PubMed, Embase, Cochrane Library, Web of Science, and Medline (up to 3 January 2018). Fifteen studies which matched our inclusion criteria with a total of 920 patients for overall survival and 867 patients for clinicopathological characteristics were included in this meta-analysis. Pooled hazard ratios (HR) and odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were calculated to summarize the effects. Our results suggested that high expression levels of XIST were associated with unfavorable overall survival in cancer patients (pooled HR = 1.81, 95% CI: 1.45–2.26). Additionally, we found that XIST was more valuable in digestive system tumors (pooled HR = 2.24, 95% CI: 1.73–2.92) than in non-digestive system tumors (pooled HR = 1.22, 95% CI: 0.60–2.45). Furthermore, elevated expression levels of XIST were connected with distant metastasis and tumor stage. XIST was correlated with poor prognosis, which suggested that XIST might serve as a novel predictive biomarker for cancer patients, especially for patients of digestive system tumors.

scholarly journals The Arabidopsis Hypoxia Inducible AtR8 Long Non-Coding RNA also Contributes to Plant Defense and Root Elongation Coordinating with WRKY Genes under Low Levels of Salicylic Acid

2020 ◽  
Vol 6 (1) ◽  
pp. 8
Author(s):  
Shuang Li ◽  
Saraswati Nayar ◽  
HuiYuan Jia ◽  
Sanjay Kapoor ◽  
Juan Wu ◽  
...  
Keyword(s):  
Salicylic Acid ◽  
Pseudomonas Syringae ◽  
Root Elongation ◽  
Early Stage ◽  
Flowering Plant ◽  
Stage Of Development ◽  
Non Coding Rna ◽  
Pathogenesis Related ◽  
Low Levels ◽  
Long Non Coding Rna

AtR8 lncRNA was previously identified in the flowering plant Arabidopsis thaliana as an abundant Pol III-transcribed long non-coding RNA (lncRNA) of approximately 260 nt. AtR8 lncRNA accumulation is responsive to hypoxic stress and salicylic acid (SA) treatment in roots, but its function has not yet been identified. In this study, microarray analysis of an atr8 mutant and wild-type Arabidopsis indicated a strong association of AtR8 lncRNA with the defense response. AtR8 accumulation exhibited an inverse correlation with an accumulation of two WRKY genes (WRKY53/WRKY70) when plants were exposed to exogenous low SA concentrations (20 µM), infected with Pseudomonas syringae, or in the early stage of development. The highest AtR8 accumulation was observed 5 days after germination, at which time no WRKY53 or WRKY70 mRNA was detectable. The presence of low levels of SA resulted in a significant reduction of root length in atr8 seedlings, whereas wrky53 and wrky70 mutants exhibited the opposite phenotype. Taken together, AtR8 lncRNA participates in Pathogenesis-Related Proteins 1 (PR-1)-independent defense and root elongation, which are related to the SA response. The mutual regulation of AtR8 lncRNA and WRKY53/WRKY70 is mediated by Nonexpressor of Pathogenesis-Related Gene 1 (NPR1).

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