The Study of Proliferation Relative Long Non-Coding RNA in CD59- Cell from Paroxysmalnocturnal Hemoglobinuria Patients

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonogenic disease of hematopoietic stem cells. LncRNA has a wide range of biological functions, including regulation of gene expression, cell differentiation, cell proliferation and substance metabolism.LncRNA maybe contribute to the proliferation of PNH clone. Methods: PNH clone (CD59-cells) and (CD59+cells) from PNH patients were sorted and analyzed by RNA sequencing in 5 PNH patients. The results were analyzed by KEGG, we focus on the proliferation relative pathway-NF-kB pathway. The mRNA(TAB2, TLR4, LYN,CFLAR, TNFAIP3, PTGS2, TRIM25, CXCL8) which FPKM>10 and over 3 pathients were chosen to search out the upstream regulation LncRNA. MALAT1 and LINC01002 were screened by Co-expression. Then the expression of MALAT1 and LINC01002 in 30 PNH patients were detected by qRT-PCR to vertify the LncRNA sequencing results. Results: Transcription analysis revealed that 742 upregulation LncRNA and 3276 upregulation mRNA were identified in CD59- cells. The highly expressed NF-kB pathway mRNA (TAB2, TLR4, LYN,CFLAR, TNFAIP3, PTGS2, TRIM25, CXCL8) were analysed by LncRNA co-expression, after that MALAT1and LINC01002 were concerned with the 8 mRNA. The results of PNH primary cells (CD59-cells) showed that the level of MALAT1and LINC01002 expression was significantly higher than that of the CD59+ cell in 30 PNH patients (p<0.05). Conclusion: MALAT1and LINC01002 seems to be involved in the proliferation of PNH clones. Its mechanism of action in patients with PNH needs further study. Disclosures No relevant conflicts of interest to declare.

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Long Non-Coding RNA FAM157C Contributed to Clonal Proliferation in Paroxysmal Nocturnal Hemoglobinuria

10.21203/rs.3.rs-147083/v1 ◽

2021 ◽

Author(s):

Honglei Wang ◽

Hui Liu ◽

Yingying Chen ◽

Liyan Li ◽

Zhaoyun Liu ◽

...

Keyword(s):

Paroxysmal Nocturnal Hemoglobinuria ◽

Regulation Of Gene Expression ◽

Hematopoietic Stem ◽

Clonal Proliferation ◽

Non Coding Rna ◽

Wide Range ◽

Differentiation And Proliferation ◽

Clone Cells ◽

First Time ◽

Pnh Clone

Abstract Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disease of hematopoietic stem cells. However, the mechanism of proliferative advantage of PNH clone is unclear. Long noncoding RNAs (LncRNAs) have a wide range of biological functions, including regulation of gene expression, cell differentiation, and proliferation, while its role in PNH remains unclear. Methods: In our study, CD59－and CD59+ granulocytes and monocytes from 5 PNH patients were sorted, and LncRNAs and mRNAs were detected by RNA sequencing. The proliferation-related NF-κB pathway was focused on. A total of 8 mRNAs and 5 LncRNAs were verified by qRT-PCR, and analyzed the correlation with clinical data. Meanwhile, the function of LncRNA was studied.Results: LncRNA FAM157C were verified to be upregulated in PNH clone cells, which were positively correlated with LDH level and CD59- granulated and monocytes cells ratio. After knockdown of FAM157C gene in PIGA-KO-THP-1 cell line, we found that the cells were blocked in G0/G1 phase and S phase, and the apoptosis rate increased, while the proliferation ability decreased. Conclusions: LncRNA FAM157C was proved to promote PNH clone proliferation, which is the first time to explore the role of LncRNAs in PNH.

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CIRCULAR RNA – miRNA MEDIATED INTERACTION IN MYOCARDIAL INFARCTION

Journal of IMAB - Annual Proceeding (Scientific Papers) ◽

10.5272/jimab.2021272.3793 ◽

2021 ◽

Vol 27 (2) ◽

pp. 3793-3798

Author(s):

Yordanka Doneva ◽

◽

Veselin Valkov ◽

Yavor Kashlov ◽

Galya Mihaylova ◽

...

Keyword(s):

Gene Expression ◽

Myocardial Infarction ◽

Circular Rna ◽

Biological Functions ◽

Non Coding Rna ◽

Circular Structure ◽

Wide Range ◽

Non Coding Rnas ◽

Long Non Coding Rna

Circular RNA (circRNAs) belong to the long non-coding RNA family, but unlike the linear RNA in circular RNA, the 3’ and 5’ end in the RNA molecule are joined together, forming their circular structure. Until recently, circRNAs have been believed to be a side product of splicing, but now it is known that they have a wide range of biological functions, from regulators of gene expression to regulators of other non-coding RNAs - microRNAs (miRNAs). CircRNAs have the potential of being therapeutic targets and biomarkers for diseases. There are little data and only several investigations about this type of RNAs in myocardial infarction in humans. This review summarizes the role of some new circRNA – miRNA interactions in the development of Myocardial Infarction.

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

Molecular Neurobiology ◽

10.1007/s12035-021-02474-y ◽

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.

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Abstract TMP25: Long Non-Coding RNA Mediates Stroke-Induced Neurogenesis

Stroke ◽

10.1161/str.51.suppl_1.tmp25 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Baoyan Fan ◽

Wanlong Pan ◽

Xinli Wang ◽

Michael Chopp ◽

Zheng Gang Zhang ◽

...

Keyword(s):

Cell Cycle ◽

Regulation Of Gene Expression ◽

Artery Occlusion ◽

Loss Of Function ◽

Bioinformatics Analyses ◽

Guide Rna ◽

Non Coding Rna ◽

Cerebral Artery Occlusion ◽

Long Non Coding Rna

Background and Purpose: Adult neurogenesis contributes to functional recovery after stroke. Long non-coding RNAs (lncRNAs) regulate stem cell self-renewal and differentiation. However, the role of lncRNAs in stroke-induced neurogenesis remains unknown. Methods and Results: Using lncRNA array and in situ hybridization, we analyzed lncRNA profiles of adult neural stem cells (NSCs) isolated from the subventricular zone neurogenic region in rats subjected to middle cerebral artery occlusion. We found that H19 was the most highly upregulated lncRNA (19 fold) in ischemic NSCs compared with non-ischemic NSCs. Reduction of endogenous H19 in NSCs by CRISPR-Cas9 genome editing significantly decreased the proliferation and increased the apoptosis of ischemic NSCs, as assayed by the number of BrdU + cells (56±5% vs 22±3%, p<0.01, n=3) and Caspase-3/7 activity compared to NSCs transfected with scrambled small guide RNA (sgRNA). Knockdown of H19 significantly decreased the number of Tuj1 + neuroblasts (8±2% vs 5±0.4%, p<0.01, n=3) and NG 2 + oliogodendrocyte progenitor cells (10±1% vs 5±0.3%, p<0.01, n=3), suggesting that deletion of H19 suppresses the proliferation and survival and blocks the differentiation of NSCs into neurons and oligodendrocytes. Additional RNA-sequencing and bioinformatics analyses revealed that genes deregulated by H19 knockdown were involved in transcription, apoptosis, proliferation, cell cycle and response to hypoxia. Western blot analysis validated that loss-of-function and gain-of-function of H19 significantly increased and reduced, respectively, the transcription of cell cycle-related genes including p27. Using ChIRP assay, we found that upregulated H19 in NSCs was physically associated with EZH2 which catalyzes the repressive H3K27me3 histone marker. Knockdown of H19 significantly reduced the enrichment of H3K27me3 at the promoter of p27, leading to the upregulation of p27 expression and consequently inhibition of NSC proliferation. Conclusions: H19 mediates stroke-induced neurogenesis by regulating genes involved in cell cycle and survival through the interaction with chromatin remodeling proteins. Our data provide novel insights into epigenetic regulation of gene expression by lncRNA in neurogenesis.

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Paroxysmal Nocturnal Hemoglobinuria Clones Are Infrequent in Hepatitis-Associated Aplastic Anemia at the Time of Diagnosis

Blood ◽

10.1182/blood-2019-125620 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5016-5016

Author(s):

Wenrui Yang ◽

Xin Zhao ◽

Guangxin Peng ◽

Li Zhang ◽

Liping Jing ◽

...

Keyword(s):

Aplastic Anemia ◽

Paroxysmal Nocturnal Hemoglobinuria ◽

Conflicts Of Interest ◽

Bone Marrow Failure ◽

Clonal Evolution ◽

Extrinsic Factors ◽

Clone Size ◽

Hematopoietic Stem ◽

Over Time ◽

Pnh Clone

Aplastic anemia (AA) is an immune-mediated bone marrow failure, resulting in reduced number of hematopoietic stem and progenitor cells and pancytopenia. The presence of paroxysmal nocturnal hemoglobinuria (PNH) clone in AA usually suggests an immunopathogenesis in patients. However, when and how PNH clone emerge in AA is still unclear. Hepatitis associated aplastic anemia (HAAA) is a special variant of AA with a clear disease course and relatively explicit immune pathogenesis, thus serves as a good model to explore the emergence and expansion of PNH clone. To evaluate the frequency and clonal evolution of PNH clones in AA, we retrospectively analyzed the clinical data of 90 HAAA patients that were consecutively diagnosed between August 2006 and March 2018 in Blood Diseases Hospital, and we included 403 idiopathic AA (IAA) patients as control. PNH clones were detected in 8 HAAA patients (8.9%,8/90) at the time of diagnosis, compared to 18.1% (73/403) in IAA. Eight HAAA patients had PNH clone in granulocytes with a median clone size of 3.90% (1.09-12.33%), and 3 patients had PNH clone in erythrocytes (median 4.29%, range 2.99-10.8%). Only one HAAA patients (1/8, 12.5%) had a PNH clone larger than 10%, while 24 out of 73 IAA patients (32.9%) had larger PNH clones. Taken together, we observed a less frequent PNH clone with smaller clone size in HAAA patients, compared to that in IAAs. We next attempted to find out factors that associated with PNH clones. We first split patients with HAAA into two groups based on the length of disease history (≥3 mo and < 3mo). There were more patients carried PNH clone in HAAA with longer history (21.4%, 3/14) than patients with shorter history (6.6%, 5/76), in line with higher incidence of PNH clone in IAA patients who had longer disease history. Then we compared the PNH clone incidence between HAAA patients with higher absolute neutrophil counts (ANC, ≥0.2*109/L) and lower ANC (< 0.2*109/L). Interestingly, very few VSAA patients developed PNH clone (5%, 3/60), while 16.7% (5/30) of non-VSAA patients had PNH clone at diagnosis. We monitored the evolution of PNH clones after immunosuppressive therapy, and found increased incidence of PNH clone over time. The overall frequency of PNH clone in HAAA was 20.8% (15/72), which was comparable to that in IAA (27.8%, 112/403). Two thirds of those new PNH clones occurred in non-responders in HAAA. In conclusion, PNH clones are infrequent in HAAA compared to IAA at the time of diagnosis, but the overall frequency over time are comparable between the two groups of patients. In SAA/VSAA patients who are under the activated abnormal immunity, longer clinical course and relatively adequate residual hematopoietic cells serve as two important extrinsic factors for HSCs with PIGA-mutation to escape from immune attack and to expand. Disclosures No relevant conflicts of interest to declare.

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HOTAIR: An Oncogenic Long Non-Coding RNA in Human Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000490131 ◽

2018 ◽

Vol 47 (3) ◽

pp. 893-913 ◽

Cited By ~ 87

Author(s):

Qing Tang ◽

Swei Sunny Hann

Keyword(s):

Drug Resistance ◽

Human Cancer ◽

Critical Role ◽

Stem Cell Differentiation ◽

Human Diseases ◽

Biological Functions ◽

Protein Coding ◽

Non Coding Rna ◽

And Function ◽

Long Non Coding Rna

Long non-coding RNAs (LncRNAs) represent a novel class of noncoding RNAs that are longer than 200 nucleotides without protein-coding potential and function as novel master regulators in various human diseases, including cancer. Accumulating evidence shows that lncRNAs are dysregulated and implicated in various aspects of cellular homeostasis, such as proliferation, apoptosis, mobility, invasion, metastasis, chromatin remodeling, gene transcription, and post-transcriptional processing. However, the mechanisms by which lncRNAs regulate various biological functions in human diseases have yet to be determined. HOX antisense intergenic RNA (HOTAIR) is a recently discovered lncRNA and plays a critical role in various areas of cancer, such as proliferation, survival, migration, drug resistance, and genomic stability. In this review, we briefly introduce the concept, identification, and biological functions of HOTAIR. We then describe the involvement of HOTAIR that has been associated with tumorigenesis, growth, invasion, cancer stem cell differentiation, metastasis, and drug resistance in cancer. We also discuss emerging insights into the role of HOTAIR as potential biomarkers and therapeutic targets for novel treatment paradigms in cancer.

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Identification of Potential Long Non-coding RNA Expression Quantitative Trait Methylations in Lung Adenocarcinoma and Lung Squamous Carcinoma

Frontiers in Genetics ◽

10.3389/fgene.2020.602035 ◽

2020 ◽

Vol 11 ◽

Author(s):

Xiaohong Wu ◽

Yue Gao ◽

Jianlong Bu ◽

Lin Deng ◽

Pinyi Zhang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Quantitative Trait ◽

Regulatory Networks ◽

Squamous Carcinoma ◽

Drug Repurposing ◽

Cancer Pathogenesis ◽

Non Coding Rna ◽

Wide Range ◽

Lung Squamous Carcinoma ◽

Long Non Coding Rna

There are associations between DNA methylation and the expression of long non-coding RNA (lncRNA), also known as lncRNA expression quantitative trait methylations (lnc-eQTMs). Lnc-eQTMs may induce a wide range of carcinogenesis pathways. However, lnc-eQTMs have not been globally identified and studied, and their roles in lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) are largely unknown. In the present study, we identified some differential methylation sites located in genes of long intergenic non-coding RNAs (lincRNAs) and other types of lncRNAs in LUAD and LUSC. An integrated pipeline was established to construct two global cancer-specific regulatory networks of lnc-eQTMs in LUAD and LUSC. The associations between eQTMs showed common and specific features between LUAD and LUSC. Some lnc-eQTMs were also related with survival in LUAD- and LUSC-specific regulatory networks. Lnc-eQTMs were associated with cancer-related functions, such as lung epithelium development and vasculogenesis by functional analysis. Drug repurposing analysis revealed that these lnc-eQTMs may mediate the effects of some anesthesia-related drugs in LUAD and LUSC. In summary, the present study elucidates the roles of lnc-eQTMs in LUAD and LUSC, which could improve our understanding of lung cancer pathogenesis and facilitate treatment.

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