scholarly journals Reciprocal modulation of long noncoding RNA EMS and p53 regulates tumorigenesis

2022 ◽  
Vol 119 (3) ◽  
pp. e2111409119
Author(s):  
Chenfeng Wang ◽  
Yang Yang ◽  
Xianning Wu ◽  
Jingxin Li ◽  
Kaiyue Liu ◽  
...  
Keyword(s):  
Long Noncoding Rna ◽  
Transcriptional Repression ◽  
Messenger Rna ◽  
Noncoding Rna ◽  
Critical Role ◽  
P53 Expression ◽  
P53 Signaling ◽  
Element Binding Protein ◽  
Mrna Polyadenylation ◽  
P53 Mrna

p53 plays a central role in tumor suppression. Emerging evidence suggests long noncoding RNA (lncRNA) as an important class of regulatory molecules that control the p53 signaling. Here, we report that the oncogenic lncRNA E2F1 messenger RNA (mRNA) stabilizing factor (EMS) and p53 mutually repress each other’s expression. EMS is negatively regulated by p53. As a direct transcriptional repression target of p53, EMS is surprisingly shown to inhibit p53 expression. EMS associates with cytoplasmic polyadenylation element-binding protein 2 (CPEB2) and thus, disrupts the CPEB2–p53 mRNA interaction. This disassociation attenuates CPEB2-mediated p53 mRNA polyadenylation and suppresses p53 translation. Functionally, EMS is able to exert its oncogenic activities, at least partially, via the CPEB2–p53 axis. Together, these findings reveal a double-negative feedback loop between p53 and EMS, through which p53 is finely controlled. Our study also demonstrates a critical role for EMS in promoting tumorigenesis via the negative regulation of p53.

XIST: A Meaningful Long Noncoding RNA in NSCLC Process

2020 ◽  
Vol 26 ◽  
Author(s):  
Yujie Shen ◽  
Yexiang Lin ◽  
Kai Liu ◽  
Jinlan Chen ◽  
Juanjuan Zhong ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Critical Role ◽  
Biological Functions ◽  
Potential Therapeutic Target ◽  
Considerable Evidence ◽  
Lncrna Xist ◽  
Nsclc Patients ◽  
The Relationship

Background: A number of studies have proposed that lncRNA XIST plays a role in the development and chemosensitivity of NSCLC. Besides, XIST may become a potential therapeutic target for NSCLC patients. The aim of this review is to reveal the biological functions and exact mechanisms of XIST in NSCLC. Methods: In this review, relevant researches involving in the relationship between XIST and NSCLC are collected through systematic retrieval of PubMed Results: XIST is an oncogene in NSCLC and is abnormally upregulated in NSCLC tissues. Considerable evidence has shown that XIST exerts a critical role in the proliferation, invasion, migration, apoptosis and chemosensitivity of NSCLC cells. XIST mainly functions as a ceRNA in NSCLC process, while XIST also functions at transcriptional levels. Conclusion: LncRNA XIST has potential to become a novel biomolecular marker of NSCLC and a therapeutic target for NSCLC.

scholarly journals KDM6A mediated expression of the long noncoding RNA DINO causes TP53 tumor suppressor stabilization in Human Papillomavirus type 16 E7 expressing cells

2020 ◽  
Author(s):  
Surendra Sharma ◽  
Karl Munger
Keyword(s):  
Cell Death ◽  
Tumor Suppressor ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Critical Role ◽  
Metabolic Stress ◽  
Dominant Negative ◽  
Missing Link ◽  
Hpv16 E6 ◽  
E6 And E7

ABSTRACTHPV16 E7 has long been noted to stabilize the TP53 tumor suppressor. However, the molecular mechanism of TP53 stabilization by HPV16 E7 has remained obscure and can occur independent of E2F regulated MDM2 inhibitor, p14ARF. Here, we report that the Damage Induced Noncoding (DINO) lncRNA (DINOL) is the missing link between HPV16 E7 and increased TP53 levels. DINO levels are decreased in cells where TP53 is inactivated, either by HPV16 E6, expression of a dominant negative TP53 minigene or by TP53 depletion. DINO levels are increased in HPV16 E7 expressing cells. HPV16 E7 causes increased DINO expression independent of RB1 degradation and E2F1 activation. Similar to the adjacent CDKN1A locus, DINO expression is regulated by the histone demethylase, KDM6A. DINO stabilizes TP53 in HPV16 E7 expressing cells and as a TP53 transcriptional target, DINO levels further increase. Similar to other oncogenes such as adenovirus E1A or MYC, HPV16 E7 expressing cells are sensitized to cell death under conditions of metabolic stress and in the case of E7, this has been linked to TP53 activation. Consistent with earlier studies, we show that HPV16 E7 expressing keratinocytes are highly sensitive to metabolic stress induced by the antidiabetic drug, metformin. Metformin sensitivity of HPV16 E7 expressing cells is rescued by DINO depletion. This work identifies DINO as a critical mediator TP53 stabilization and activation in HPV16 E7 expressing cells.IMPORTANCEViral oncoproteins, including HPV16 E6 and E7 have been instrumental in elucidating the activities of cellular signaling networks including those governed by the TP53 tumor suppressor. Our study demonstrates that the long noncoding RNA DINO is the long sought missing link between HPV16 E7 and elevated TP53 levels. Importantly, the TP53 stabilizing DINO plays a critical role in the predisposition of HPV16 E7 expressing cells to cell death under metabolic stress conditions from metformin treatment.

Abstract 3543: A long noncoding RNA plays a critical role in Bcr-Abl-mediated cellular transformation

2014 ◽  
Author(s):  
Guijie Guo ◽  
Qingzheng Kang ◽  
Qinghuang Chen ◽  
Ouyang Jing ◽  
Jilong Chen
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Critical Role ◽  
Cellular Transformation

scholarly journals Transcriptome analysis of messenger RNA and long noncoding RNA related to different developmental stages of tail adipose tissues of sunite sheep

2020 ◽  
Author(s):  
Xige He ◽  
Rihan Wu ◽  
Yueying Yun ◽  
Xia Qin ◽  
Lu Chen ◽  
...  
Keyword(s):  
Long Noncoding Rna ◽  
Messenger Rna ◽  
Noncoding Rna ◽  
Target Genes ◽  
Early Stage ◽  
Expression Profiles ◽  
Theoretical Data ◽  
Differentially Expressed ◽  
Growth Stages ◽  
Complex Biological Process

Abstract Background: Sunite sheep are a fat-tailed sheep species with a low percentage of intramuscular fat and good quality lean meat, and their tail fat can be used as a source of dietary fat by humans. To understand the potential regulatory mechanism of different growth stages of tail fat in Sunite sheep, we performed high-throughput RNA sequencing to characterize the long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression profiles of the sheep tail fat at the age of 6 months, 18 months, and 30 months.Results: A total of 223 differentially expressed genes (DEGs) and 148 differentially expressed lncRNAs were found in the tail fat of 6-, 18-, and 30-month-old sheep (false discovery rate < 0.05, |Fold Change| ≥ 2). Based on the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, we found that fat-related DEGs were mainly expressed at 6 months of age, and gradually decreased at 18 and 30 months of age. The target gene prediction analysis shows that most of the lncRNAs target more than 20 mRNAs as their trans-regulators (53 mRNAs at most). Further, we obtained several fat-related differentially-expressed target genes; these target genes interact with different differentially expressed lncRNAs at various ages and play an important role in the development of tail fat. Based on the DEGs and differentially expressed lncRNAs, we established three co-expression networks for each comparison group. Conclusions: Finally, we conclude that the development of the sheep tail fat is more active during the early stage of growth and gradually decreases with the increase in age. The mutual regulation of lncRNAs and mRNAs may play a key role in this complex biological process, and our findings will provide some basic theoretical data for future studies on tail fat development of fat-tailed sheep.

scholarly journals Comprehensive analysis of the long noncoding RNA-associated competitive endogenous RNA network in the osteogenic differentiation of periodontal ligament stem cells

BMC Genomics ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Lingzhi Lai ◽  
Zhaodan Wang ◽  
Yihong Ge ◽  
Wei Qiu ◽  
Buling Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Long Noncoding Rna ◽  
Periodontal Ligament ◽  
Messenger Rna ◽  
Noncoding Rna ◽  
Periodontal Regeneration ◽  
Tgf Beta ◽  
Periodontal Ligament Stem Cells ◽  
Cerna Network ◽  
Significant Expression

Abstract Backgroud The mechanism implicated in the osteogenesis of human periodontal ligament stem cells (PDLSCs) has been investigated for years. Previous genomics data analyses showed that long noncoding RNA (lncRNA), microRNA (miRNA) and messenger RNA (mRNA) have significant expression differences between induced and control human PDLSCs. Competing for endogenous RNAs (ceRNA), as a widely studied mechanism in regenerative medicine, while rarely reported in periodontal regeneration. The key lncRNAs and their ceRNA network might provide new insights into molecular therapies of periodontal regeneration based on PDLSCs. Results Two networks reflecting the relationships among differentially expressed RNAs were constructed. One ceRNA network was composed of 6 upregulated lncRNAs, 280 upregulated mRNAs, and 18 downregulated miRNAs. The other network contained 33 downregulated lncRNAs, 73 downregulated mRNAs, and 5 upregulated miRNAs. Functional analysis revealed that 38 GO terms and 8 pathways related with osteogenesis were enriched. Twenty-four osteogenesis-related gene-centred lncRNA-associated ceRNA networks were successfully constructed. Among these pathways, we highlighted MAPK and TGF-beta pathways that are closely related to osteogenesis. Subsequently, subnetworks potentially linking the GO:0001649 (osteoblast differentiation), MAPK and TGF-beta pathways were constructed. The qRT-PCR validation results were consistent with the microarray analysis. Conclusion We construct a comprehensively identified lncRNA-associated ceRNA network might be involved in the osteogenesis of PDLSCs, which could provide insights into the regulatory mechanisms and treatment targets of periodontal regeneration.

A novel messenger RNA and long noncoding RNA signature associated with the progression of nonmuscle invasive bladder cancer

2018 ◽  
Vol 120 (5) ◽  
pp. 8101-8109 ◽  
Author(s):  
Yu‐hui He ◽  
Yi‐sen Deng ◽  
Pan‐xin Peng ◽  
Ning Wang ◽  
Jian‐feng Wang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Long Noncoding Rna ◽  
Messenger Rna ◽  
Noncoding Rna ◽  
Invasive Bladder Cancer ◽  
Nonmuscle Invasive Bladder Cancer ◽  
Rna Signature

scholarly journals Long noncoding RNA LSINCT5 promotes endometrial carcinoma cell proliferation, cycle, and invasion by promoting the Wnt/β-catenin signaling pathway via HMGA2

2019 ◽  
Vol 11 ◽  
pp. 175883591987464 ◽  
Author(s):  
Hongye Jiang ◽  
Yong Li ◽  
Jie Li ◽  
Xuyu Zhang ◽  
Gang Niu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Endometrial Carcinoma ◽  
Signaling Pathway ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Critical Role ◽  
Migration And Invasion ◽  
Migration Assay

Background: A review of the evidence has indicated the critical role of long noncoding RNA (lncRNA) LSINCT5 in a large number of human cancers. However, the mechanistic involvement of LSINCT5 in endometrial carcinoma (EC) is still unknown. Here the authors aim to characterize the expression status of LSINCT5 and elucidate its mechanistic relevance to EC. Methods: Relative expression of LSINCT5 and HMGA2 were quantified by a real-time polymerase chain reaction. SiRNAs were employed to specifically knockdown endogenous LSINCT5 in EC cells. Cell proliferation was measured with Cell Count Kit-8 kit (CCK-8, Dojindo, Kumamoto, Japan) and cell growth was assessed by a colony formation assay. The cell cycle was analyzed with propidium iodide (PI) staining. Apoptotic cells were determined by flow cytometry after Annexin V/PI double-staining. Cell migration was evaluated by a wound-healing assay, and cell invasion was assessed using a transwell migration assay. The protein levels of HMGA2, Wnt3a, p-β-catenin, c-myc, β-actin, and GAPDH were determined by western blot. Results: The authors observed positively correlated and aberrantly up-regulated LSINCT5 and HMGA2 in EC. LSINCT5 deficiency significantly inhibited cell proliferation, cell cycle progression, and induced apoptosis. Meanwhile, cell migration and invasion were greatly compromised by the LSINCT5 knockdown. LSINCT5 stabilized HMGA2, which subsequently stimulated activation of Wnt/β-catenin signaling and consequently contributed to the oncogenic properties of LSINCT5 in EC. Conclusions: Our data uncovered the oncogenic activities and highlighted the mechanistic contributions of the LSINCT5-HMGA2-Wnt/β-catenin signaling pathway in EC.

scholarly journals A long noncoding RNA,LncMyoD, modulates chromatin accessibility to regulate muscle stem cell myogenic lineage progression

2020 ◽  
Vol 117 (51) ◽  
pp. 32464-32475
Author(s):  
Anqi Dong ◽  
Christopher B. Preusch ◽  
Wai-Kin So ◽  
Kangning Lin ◽  
Shaoyuan Luan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Target Genes ◽  
Myogenic Differentiation ◽  
Critical Role ◽  
Chromatin Accessibility ◽  
Mechanistic Study ◽  
Muscle Stem Cells ◽  
Myogenic Lineage

Epigenetics regulation plays a critical role in determining cell identity by controlling the accessibility of lineage-specific regulatory regions. In muscle stem cells, epigenetic mechanisms of how chromatin accessibility is modulated during cell fate determination are not fully understood. Here, we identified a long noncoding RNA,LncMyoD, that functions as a chromatin modulator for myogenic lineage determination and progression. The depletion ofLncMyoDin muscle stem cells led to the down-regulation of myogenic genes and defects in myogenic differentiation.LncMyoDexclusively binds with MyoD and not with other myogenic regulatory factors and promotes transactivation of target genes. The mechanistic study revealed that loss ofLncMyoDprevents the establishment of a permissive chromatin environment at myogenic E-box–containing regions, therefore restricting the binding of MyoD. Furthermore, the depletion ofLncMyoDstrongly impairs the reprogramming of fibroblasts into the myogenic lineage. Taken together, our study shows thatLncMyoDassociates with MyoD and promotes myogenic gene expression through modulating MyoD accessibility to chromatin, thereby regulating myogenic lineage determination and progression.

Sign in / Sign up

Export Citation Format

Share Document