scholarly journals A correlation between Long noncoding RNA and unpaired DNA silencing in Drosophila

2016 ◽  
Author(s):  
Manika Pal-Bhadra ◽  
Indira Bag ◽  
Sreerangam N.C. L.V Pushpavalli ◽  
Avadhesha Surolia ◽  
Utpal Bhadra
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Gene Dosage ◽  
Genetic Material ◽  
Transcriptional Silencing ◽  
Transcriptional Level ◽  
Loss Of Function ◽  
Gene Dosage Effect ◽  
Copy Numbers ◽  
Dna Silencing

SUMMARYHybrid transgenes are often recognized as foreign genetic material by cell surveillance mechanisms and are repressed in expression inversely to their copy numbers. Here, we compare the expression of multiple Adh-promoter-white reporter (Adh-w) inserts in paired and unpaired configurations in Drosophila somatic cells. The unpaired copies exhibit a clear repression at the transcriptional level relative to paired gene dosage effect, which is dependent upon long noncoding RNA, Polycomb and piwi. Deficiency mapping using Adh-w constructs showed that a minimal sequence of 532 bp of the Adh promoter is required for unpaired DNA silencing. Long noncoding RNA detected from this region of the Adh promoter is abundant in the unpaired condition. It serves as a docking site for at least two proteins POLYCOMB and Piwi that are essential for active transcriptional silencing. The lesser abundance of noncoding RNAs in the paired configuration only allows PC binding. An active RNA-Protein complex binds to unpaired copies. The loss-of-function piwi mutation relieves transcriptional silencing even in association with POLYCOMB. It suggests that functional RNA-Piwi complex might create a silencing driven chromatin configuration by accumulating histone modifying enzymes at the Adh-w promoter target. This distinct transcriptional silencing that is stronger for unpaired DNA represents a novel mechanism to repress new transposon and foreign DNA insertions for protection of genome integrity.

scholarly journals Long noncoding RNA SNHG25 promotes the malignancy of endometrial cancer by sponging microRNA-497-5p and increasing FASN expression

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yuhua He ◽  
Shuifang Xu ◽  
Yi Qi ◽  
Jinfang Tian ◽  
Fengying Xu
Keyword(s):  
Endometrial Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Fatty Acid Synthase ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Study Cohort ◽  
Loss Of Function ◽  
Ec Cells

Abstract Background Small nucleolar RNA host gene 25 (SNHG25), a long noncoding RNA, has been well-studied in epithelial ovarian cancer. However, the specific functions of SNHG25 in endometrial cancer (EC) have not been studied yet. In this study, we aimed to elucidate the clinical significance of SNHG25 in EC and determine the regulatory activity of SNHG25 on the tumor-associated EC phenotype. We also thoroughly explored the molecular mechanisms underlying SNHG25 function in EC. Methods Gene expression was measured using quantitative real-time polymerase chain reaction. The detailed functions of SNHG25 in EC were examined by performing loss-of-function experiments. Moreover, the regulatory mechanisms involving SNHG25, microRNA-497-5p, and fatty acid synthase (FASN) were unveiled using the luciferase reporter assay and RNA immunoprecipitation. Results We observed a high level of SNHG25 in EC using the TCGA dataset and our study cohort. Patients with a high SNHG25 level had shorter overall survival than those with a low SNHG25 level. SNHG25 deficiency resulted in tumor-repressing activities in EC cells by decreasing cell proliferation, migration, and invasion and promoting cell apoptosis. Furthermore, the function of SNHG25 depletion in impairing tumor growth in vivo was confirmed. SNHG25 sequestered miR-497-5p as a competing endogenous RNA in EC and consequently positively regulated FASN expression. Thus, the decrease in miR-497-5p or increase in FASN could neutralize the modulatory actions of SNHG25 knockdown in EC cells. Conclusions The depletion of SNHG25 impedes the oncogenicity of EC by targeting the miR-497-5p/FASN axis. The newly elucidated SNHG25/miR-497-5p/FASN pathway may be a promising target for the molecular-targeted management of EC.

Knockdown of long noncoding RNA AC245100.4 inhibits the tumorigenesis of prostate cancer cells via the STAT3/NR4A3 axis

Epigenomics ◽  
2021 ◽  
Author(s):  
Chi Liu ◽  
Ping Lin ◽  
Jiabin Zhao ◽  
Hui Xie ◽  
Rou Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Rna Sequencing ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Transcriptional Repressor ◽  
Sequencing Analysis ◽  
Loss Of Function ◽  
Prostate Cancer Cells ◽  
Rna Immunoprecipitation

Aim: To explore the role and mechanism of long noncoding RNA AC245100.4 and NR4A3 in prostate cancer (PCa). Methods: RNA-sequencing analysis was used to detect the downstream genes of AC245100.4. A series of gain- and loss-of-function approaches were used to investigate the roles of AC245100.4 and NR4A3. RNA immunoprecipitation was performed to examine the interaction between AC245100.4 and STAT3. Results: AC245100.4 was significantly upregulated in PCa cells and tissues. Knockdown of AC21500.4 significantly inhibited the tumorigenesis of PCa cells. Mechanistically, AC245100.4 deregulated the transcription of NR4A3 via increasing p-STAT3, which acted as a transcriptional repressor of NR4A3. Conclusion: Knockdown of lncRNA AC245100.4 inhibits the tumorigenesis of PCa cells via the STAT3/ NR4A3 axis.

scholarly journals Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Lovorka Stojic ◽  
Malwina Niemczyk ◽  
Arturo Orjalo ◽  
Yoko Ito ◽  
Anna Elisabeth Maria Ruijter ◽  
...  
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Transcriptional Silencing

scholarly journals Complex networks of miRNA-transcription factors mediate gene dosage compensation in aneuploid cancer

2020 ◽  
Author(s):  
ManSai Acón ◽  
Guillermo Oviedo ◽  
Edwin Baéz ◽  
Gloriana Vásquez-Vargas ◽  
José Guevara-Coto ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Complex Networks ◽  
Dosage Compensation ◽  
Computational Models ◽  
Therapeutic Potential ◽  
Gene Dosage ◽  
Cancer Cell Line ◽  
Transcriptional Level ◽  
Negative Effects ◽  
Copy Numbers

AbstractCancer complexity is consequence of enormous genomic instability leading to aneuploidy, a hallmark of most cancers. We hypothesize that dosage compensation of critical genes could arise from systems-level properties of complex networks of microRNAs (miRNA) and transcription factors (TF) as a way for cancer cells to withstand the negative effects of aneuploidy. We studied gene dosage compensation at the transcriptional level on data of the NCI-60 cancer cell line panel with the aid of computational models to identify candidate genes with low tolerance to variation in gene expression despite high variation in copy numbers. We identified a network of TF and miRNAs validated interactions with those genes to construct a mathematical model where the property of dosage compensation emerged for MYC and STAT3. Compensation was mediated by feedback and feed-forward motifs with 4 miRNAs and was dependent on the kinetic parameters of these TF-miRNA interactions, indicating that network analysis was not enough to identify this emergent property. The inhibition of miRNAs compensating MYC suggest a therapeutic potential of targeting gene dosage compensation against aneuploid cancer.

scholarly journals Long Noncoding RNA MIR4697HG Promotes Cell Growth and Metastasis in Human Ovarian Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Li-qian Zhang ◽  
Su-qing Yang ◽  
Ying Wang ◽  
Qiao Fang ◽  
Xian-jun Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Growth ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Transcriptional Level ◽  
Skov3 Cells ◽  
Phosphorylated Akt

Ovarian cancer is one of the three most common gynecological malignant tumors worldwide. The prognosis of patients suffering from this malignancy remains poor because of limited therapeutic strategies. Herein, we investigated the role of a long noncoding RNA named MIR4697 host gene (MIR4697HG) in the cell growth and metastasis of ovarian cancer. Results showed that the transcriptional level of MIR4697HG in cancerous tissues increased twofold compared with that in adjacent noncancerous tissues. MIR4697HG was differentially expressed in ovarian cancer cell lines, with the highest levels in OVCAR3 and SKOV3 cells. MIR4697HG knockdown by specific shRNA significantly inhibited cell proliferation and colony formation in both OVCAR3 and SKOC3 cells. Consistently, in a xenograft model of ovarian cancer, MIR4697HG depletion also significantly restricted tumor volumes and weights. Furthermore, MIR4697HG knockdown inhibited cell migration and invasion capacities. Invasion ability was inhibited by 58% in SKOV3 cells and 40% in OVCAR3 cells, and migration ability was inhibited by 73% in SKOV3 cells and 62% in OVCAR3 cells after MIR4697HG knockdown. MIR4697HG knockdown also caused a decrease in matrix metalloprotease-9, phosphorylated ERK, and phosphorylated AKT. These data suggested that MIR4697HG promoted ovarian cancer growth and metastasis. The aggressive role of MIR4697HG in ovarian cancer may be related to the ERK and AKT signaling pathways.

scholarly journals The PU.1-Regulated Long Noncoding RNA Lnc-MC Controls Human Monocyte/Macrophage Differentiation through Interaction with MicroRNA-199a-5p

2015 ◽  
pp. MCB.00429-15 ◽  
Author(s):  
Ming-Tai Chen ◽  
Hai-Shuang Lin ◽  
Chao Shen ◽  
Yan-Ni Ma ◽  
Fang Wang ◽  
...  
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Human Monocyte ◽  
Regulation Mechanism ◽  
Loss Of Function ◽  
Macrophage Differentiation ◽  
Hematopoietic Stem ◽  
Mechanistic Investigation ◽  
Repressive Effect

Long noncoding RNAs (lncRNAs) are emerging as important regulators in mammalian development, but little is known about their roles in monocyte/macrophage differentiation. Here we identified a long noncoding RNA MonoCyte (lnc-MC), which exhibits increased expression during monocyte/macrophage differentiation of THP-1 and HL-60 cells as well as CD34+hematopoietic stem/progenitor cells (HSPCs), and is transcriptionally activated by PU.1. Gain and loss of function assays demonstrate that lnc-MC promotes monocyte/macrophage differentiation of THP-1 cells and CD34+HSPCs. Mechanistic investigation reveals that lnc-MC acts as a competing endogenous RNA to sequester miR-199a-5p and alleviate repression on activin A receptor type 1B (ACVR1B) expression, an important regulator of monocyte/macrophage differentiation. We also noted repressive effect of miR-199a-5p on lnc-MC expression and function, but PU.1-dominant down-regulation of miR-199a-5p results in its adverse position in the reciprocal regulation between miR-199a-5p and lnc-MC. Altogether, our work uncovers that PU.1-regulated two noncoding RNAs, lnc-MC and miR-199a-5p, have opposing roles in monocyte/macrophage differentiation and during the differentiation lnc-MC further enforces PU.1's role to facilitate the process by sponging miR-199a-5p and releasing ACVR1B expression, which confers a novel regulation mechanism composed of PU.1, lnc-MC, miR-199a-5p and ACVR1B in the monocyte/macrophage differentiation.

Possible gene dosage effect of glutathione-S-transferases on atopic asthma: Using real-time PCR for quantification of GSTM1 and GSTT1 gene copy numbers

2004 ◽  
Vol 24 (3) ◽  
pp. 208-214 ◽  
Author(s):  
Charlotte Brasch-Andersen ◽  
Lene Christiansen ◽  
Qihua Tan ◽  
Annette Haagerup ◽  
J�rgen Vestbo ◽  
...  
Keyword(s):  
Real Time ◽  
Real Time Pcr ◽  
Gene Dosage ◽  
Atopic Asthma ◽  
Gene Copy ◽  
Gene Dosage Effect ◽  
Gstt1 Gene ◽  
Copy Numbers ◽  
Glutathione S Transferases ◽  
Gene Copy Numbers

scholarly journals Long Noncoding RNA MIR210HG Promotes the Warburg Effect and Tumor Growth by Enhancing HIF-1α Translation in Triple-Negative Breast Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Ye Du ◽  
Na Wei ◽  
Ruolin Ma ◽  
Shu-Heng Jiang ◽  
Dong Song
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Long Noncoding Rna ◽  
Warburg Effect ◽  
Noncoding Rna ◽  
Triple Negative ◽  
Lactate Production ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
The Warburg Effect

BackgroundHypoxia is an important environmental factor and has been correlated with tumor progression, treatment resistance and poor prognosis in many solid tumors, including triple-negative breast cancer (TNBC). Emerging evidence suggests that long noncoding RNA (lncRNA) functions as a critical regulator in tumor biology. However, little is known about the link between hypoxia and lncRNAs in TNBC.MethodsTNBC molecular profiles from The Cancer Genome Atlas (TCGA) were leveraged to identify hypoxia-related molecular alterations. Loss-of-function studies were performed to determine the regulatory role of MIR210HG in tumor glycolysis. The potential functions and mechanisms of hypoxia-MIR210HG axis were explored using qPCR, Western blotting, luciferase reporter assay, and polysome profiling.ResultsWe found that MIR210HG is a hypoxia-induced lncRNA in TNBC. Loss-of-function studies revealed that MIR210HG promoted the Warburg effect as demonstrated by glucose uptake, lactate production and expression of glycolytic components. Mechanistically, MIR210HG potentiated the metabolic transcription factor hypoxia-inducible factor 1α (HIF-1α) translation via directly binding to the 5’-UTR of HIF-1α mRNA, leading to increased HIF-1a protein level, thereby upregulating expression of glycolytic enzymes. MIR210HG knockdown in TNBC cells reduced their glycolytic metabolism and abolished their tumorigenic potential, indicating the glycolysis-dependent oncogenic activity of MIR210HG in TNBC. Moreover, MIR210HG was highly expressed in breast cancer and predicted poor clinical outcome.ConclusionOur results decipher a positive feedback loop between hypoxia and MIR210HG that drive the Warburg effect and suggest that MIR210HG may be a good prognostic marker and therapeutic target for TNBC patients.

scholarly journals Overexpression of long noncoding RNA HOXB-AS3 indicates an unfavorable prognosis and promotes tumorigenesis in epithelial ovarian cancer via Wnt/β-catenin signaling pathway

2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Xiao-hong Zhuang ◽  
Ying liu ◽  
Jin-ling Li
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cell Lines ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Loss Of Function ◽  
Independent Prognostic Marker ◽  
The Impact ◽  
Oncogenic Gene

Abstract Long noncoding RNA HOXB cluster antisense RNA 3 (HOXB-AS3) has been reported to be dysregulated in several tumors. The present study mainly aims at the investigation in how HOXB-AS3 works in epithelial ovarian cancer (EOC) and to elucidate the mechanism involved. Initially, ‘GEPIA’ was mined to examine the differential expression levels and prognostic value of HOXB-AS3 in EOC patients. The expression of HOXB-AS3 in EOC cell lines and patient specimens was examined with quantitative RT-PCR. Simultaneously, the correlation of HOXB-AS3 expression with a variety of clinicopathological factors and patient survival was analyzed. MTT, colony formation and flow cytometry assays were performed to analyze the cell viability of EOC cells. Wound healing and Transwell assays were carried out to determine EOC cells’ capability of migrating and invading. The impact of HOXB-AS3 on EMT and Wnt/β-catenin signaling was explored with the approach of Western blot. We found that in both EOC cell lines and tissues, HOXB-AS3 expression was significantly up-regulated, and its high expression was an independent prognostic marker of poor outcome for EOC patients. In vitro loss-of-function assays revealed that HOXB-AS3 knockdown inhibited EOC cells proliferation, migration, invasion and EMT, and induced EOC cells’ apoptosis. Furthermore, we validated that down-regulated HOXB-AS3 attenuated the activity of Wnt/β-catenin signaling to suppress the invasion, migration and proliferation of EOC cells. To sum up, the present study came up with the conclusion that HOXB-AS3 acts as an oncogenic gene in EOC progression through HOXB-AS3-Wnt/β-catenin signaling regulation, providing a novel insight into EOC tumorigenesis.

scholarly journals Long noncoding RNA NR2F1-AS1 stimulates the tumorigenic behavior of non-small cell lung cancer cells by sponging miR-363-3p to increase SOX4

Open Medicine ◽  
2021 ◽  
Vol 17 (1) ◽  
pp. 87-95
Author(s):  
Luming Jin ◽  
Chaoyang Chen ◽  
Lipeng Huang ◽  
Qingyu Sun ◽  
Liang Bu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Small Cell ◽  
Glutamine Metabolism ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Small Cell Lung

Abstract Long noncoding RNA (lncRNA), specifically the upregulation of lncRNA NR2F1 antisense RNA 1 (NR2F1-AS1), has been involved in the progression of non-small cell lung cancer (NSCLC), but the mechanisms that underlie this remain unclear. In this study, the expression of NR2F1-AS1, miR-363-3p, and SOX4 was assessed in NSCLC cells. A loss-of-function assay was used to measure the tumorigenicity of NSCLC cells. The glycolysis and glutamine metabolism of NSCLC cells was also measured via extracellular acidification rate, consumption of glucose and glutamine, and production of lactate and ATP. The relationships among NR2F1-AS1, miR-363-3p, and SOX4 were detected via dual-luciferase reporter assay. HK-2, GLS1, and SOX4 levels were also analyzed. We found that both NSCLC tissues and cells had higher levels of NR2F1-AS1. Silencing of NR2F1-AS1 inhibited the tumorigenicity of cells in vitro and reduced the glycolysis and glutamine metabolism of NSCLC cells. Regarding its mechanism, NR2F1-AS1 positively regulated the SOX4 level by sponging miR-363-3p. Furthermore, miR-363-3p inhibition or SOX4 overexpression reversed the repressing role of sh-NR2F1-AS1 in the tumorigenicity of NSCLC cells. In summary, NR2F1-AS1 promotes the tumorigenicity of NSCLC cells by regulating miR-363-3p/SOX4.

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