Long Noncoding RNA WT1-AS Inhibit Cell Malignancy via miR-494-3p in Glioma

Primary brain tumors are a rare occurrence in comparison to other malignancies, the most predominant form being glioma. Commonly, exposure to ionizing radiations and inheritance of associated conditions such a neurofibromatosis and tuberous sclerosis are the most common causes of development of glioma. However, understanding of the molecular mechanisms that drive glioma development is limited. We explore the role of aberration of microRNA namely miR-494-3p through long noncoding RNA WT1-AS in the development of gliomas. In this study, we found that, levels of WT1-AS were significantly reduced in glioma tissues and cell lines. The miR-494-3p levels were negatively correlated with WT1-AS levels. The cellular proliferation and invasiveness decreased in WT1-AS transfected cell lines. Further the half maximal inhibitory concentration (IC50) of chemotherapeutic agent temozolomide was significantly reduced in the presence of WT1-AS. The cotransfection of WT1-AS and miR-494-3p reduced activation of phospho-AKT (p-AKT). Expression of miR-494-3p is modulated by binding to long noncoding RNA WT1-AS. Deregulation of WT1-AS leads to aberrant expression of miR-494-3p leading to hyperactivation of AKT. This malformation may result in altering protective immune responses in malignancies. Targeting of WT1-AS, miR-494-3p, and AKT may be novel therapeutic options in treatment of glioma.

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KCNQ1OT1: An Oncogenic Long Noncoding RNA

Biomolecules ◽

10.3390/biom11111602 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1602

Author(s):

Patrice Cagle ◽

Qi Qi ◽

Suryakant Niture ◽

Deepak Kumar

Keyword(s):

Noncoding Rna ◽

Molecular Mechanisms ◽

Vital Role ◽

Migration And Invasion ◽

Biological Functions ◽

Aberrant Expression ◽

Human Cancers ◽

Oral Melanoma ◽

Opposite Strand

Long noncoding RNAs (lncRNAs) are transcripts greater than 200 nucleotides that do not code for proteins but regulate gene expression. Recent studies indicate that lncRNAs are involved in the modulation of biological functions in human disease. KCNQ1 Opposite Strand/Antisense Transcript 1 (KCNQ1OT1) encodes a lncRNA from the opposite strand of KCNQ1 in the CDKN1C/KCNQ1OT1 cluster that is reported to play a vital role in the development and progression of cancer. KCNQ1OT1 regulates cancer cell proliferation, cell cycle, migration and invasion, metastasis, glucose metabolism, and immune evasion. The aberrant expression of KCNQ1OT1 in cancer patients is associated with poor prognosis and decreased survival. This review summarizes recent literature related to the biological functions and molecular mechanisms of KCNQ1OT1 in various human cancers, including colorectal, bladder, breast, oral, melanoma, osteosarcoma, lung, glioma, ovarian, liver, acute myeloid leukemia, prostate, and gastric. We also discuss the role of KCNQ1OT1 as a promising diagnostic biomarker and a novel therapeutic target in human cancers.

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Long noncoding RNA LINC00342 promotes growth of infantile hemangioma by sponging miR-3619-5p from HDGF

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00188.2019 ◽

2019 ◽

Vol 317 (4) ◽

pp. H830-H839 ◽

Cited By ~ 8

Author(s):

Zhen Liu ◽

Zhenming Kang ◽

Yujian Dai ◽

Huiming Zheng ◽

Yingjun Wang

Keyword(s):

Cell Proliferation ◽

Endothelial Cells ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Molecular Mechanisms ◽

Rna Binding ◽

Micro Rna ◽

Luciferase Reporter ◽

Proliferation And Apoptosis

Infantile hemangiomas (IH) are a type of benign vascular neoplasm that may cause permanent scarring. Hemangioma-derived endothelial cells (HemECs) are commonly used as an in vitro model to study IH. Long noncoding RNA is a type of RNA transcript longer than 200 nucleotides that does not encode any protein. LINC00342 was discovered to regulate proliferation and apoptosis in nonsmall cell lung cancer. However, the role of LINC00342 in IH has never been reported before. Expressions of LINC00342 and miR-3619-5p were detected in proliferating versus normal skin tissues. Colony formation and Cell-Couting Kit 8 assays were carried out to study the effects on cell proliferation after knockdown and overexpression of LINC00342, respectively. Meanwhile caspase-3 activity and nucleosomal fragmentation assay were applied to detect cell apoptosis. Micro-RNA binding sites on LINC00342 and hepatoma-derived growth factor (HDGF) were predicted and confirmed via dual-luciferase reporter assay. Biotin RNA pulldown assay was used to verify the direct binding between RNA molecules. LINC00342 enhanced proliferation and inhibited apoptosis in HemECs. MiR-3619-5p targeted both LINC00342 and HDGF, where LINC00342 sponged miR-3619-5p and positively regulated HDGF. HDGF knockdown rescued the effects of LINC00342 on HemECs. The LINC00342-miR-3619-5p-HDGF signaling pathway could regulate cell proliferation and apoptosis in HemECs. NEW & NOTEWORTHY The role of LINC00342 in infantile hemangiomas has not yet been elucidated. This paper highlights the regulatory role of LINC00342 in cell proliferation and apoptosis in hemangioma-derived endothelial cells and the underlying molecular mechanisms. The findings would provide potential target for treatment of infantile hemangiomas.

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Regulatory Role of microRNAs Targeting the Transcription Co-Factor ZNF521 in Normal Tissues and Cancers

International Journal of Molecular Sciences ◽

10.3390/ijms22168461 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8461

Author(s):

Emanuela Chiarella ◽

Annamaria Aloisio ◽

Stefania Scicchitano ◽

Heather Mandy Bond ◽

Maria Mesuraca

Keyword(s):

Transcription Factor ◽

Molecular Mechanisms ◽

Transitional Cell ◽

Biological Functions ◽

Aberrant Expression ◽

Normal Tissues ◽

Novel Mirna ◽

Mirna Expression Profiling ◽

Mirna Deregulation

Powerful bioinformatics tools have provided a wealth of novel miRNA–transcription factor networks crucial in controlling gene regulation. In this review, we focus on the biological functions of miRNAs targeting ZNF521, explaining the molecular mechanisms by which the dysregulation of this axis contributes to malignancy. ZNF521 is a stem cell-associated co-transcription factor implicated in the regulation of hematopoietic, neural, and mesenchymal stem cells. The aberrant expression of ZNF521 transcripts, frequently associated with miRNA deregulation, has been detected in several tumors including pancreatic, hepatocellular, gastric, bladder transitional cell carcinomas as well as in breast and ovarian cancers. miRNA expression profiling tools are currently identifying a multitude of miRNAs, involved together with oncogenes and TFs in the regulation of oncogenesis, including ZNF521, which may be candidates for diagnostic and prognostic biomarkers of cancer.

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Involvement of the long noncoding RNA H19 in osteogenic differentiation and bone regeneration

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02149-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Zimo Zhou ◽

Mohammad Showkat Hossain ◽

Da Liu

Keyword(s):

Bone Regeneration ◽

Osteogenic Differentiation ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Osteoblast Differentiation ◽

Osteoclast Differentiation ◽

Complex Processes ◽

Osteogenic Induction ◽

Novel Target

AbstractOsteogenic differentiation and bone regeneration are complex processes involving multiple genes and multiple steps. In this review, we summarize the effects of the long noncoding RNA (lncRNA) H19 on osteogenic differentiation.Osteogenic differentiation includes matrix secretion and calcium mineralization as hallmarks of osteoblast differentiation and the absorption of calcium and phosphorus as hallmarks of osteoclast differentiation. Mesenchymal stem cells (MSCs) form osteoprogenitor cells, pre-osteoblasts, mature osteoblasts, and osteocytes through induction and differentiation. lncRNAs regulate the expression of coding genes and play essential roles in osteogenic differentiation and bone regeneration. The lncRNA H19 is known to have vital roles in osteogenic induction.This review highlights the role of H19 as a novel target for osteogenic differentiation and the promotion of bone regeneration.

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IL6 sensitizes prostate cancer to the antiproliferative effect of IFNα2 through IRF9

Endocrine Related Cancer ◽

10.1530/erc-13-0222 ◽

2013 ◽

Vol 20 (5) ◽

pp. 677-689 ◽

Cited By ~ 11

Author(s):

Holger H H Erb ◽

Regina V Langlechner ◽

Patrizia L Moser ◽

Florian Handle ◽

Tineke Casneuf ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Lines ◽

Cellular Proliferation ◽

Tissue Expression ◽

Type I ◽

Regulatory Factor ◽

Quantitative Real Time Pcr ◽

Antiproliferative Effects ◽

Protein Levels

Development and progression of prostate cancer (PCa) are associated with chronic inflammation. The cytokine interleukin 6 (IL6) can influence progression, differentiation, survival, and angiogenesis of PCa. To identify novel pathways that are triggered by IL6, we performed a gene expression profiling of two PCa cell lines, LNCaP and MDA PCa 2b, treated with 5 ng/ml IL6. Interferon (IFN) regulatory factor 9 (IRF9) was identified as one of the most prevalent IL6-regulated genes in both cell lines. IRF9 is a mediator of type I IFN signaling and acts together with STAT1 and 2 to activate transcription of IFN-responsive genes. The IL6 regulation of IRF9 was confirmed at mRNA and protein levels by quantitative real-time PCR and western blot respectively in both cell lines and could be blocked by the anti-IL6 antibody Siltuximab. Three PCa cell lines, PC3, Du-145, and LNCaP-IL6+, with an autocrine IL6 loop displayed high expression of IRF9. A tissue microarray with 36 PCa tissues showed that IRF9 protein expression is moderately elevated in malignant areas and positively correlates with the tissue expression of IL6. Downregulation and overexpression of IRF9 provided evidence for an IFN-independent role of IRF9 in cellular proliferation of different PCa cell lines. Furthermore, expression of IRF9 was essential to mediate the antiproliferative effects of IFNα2. We concluded that IL6 is an inducer of IRF9 expression in PCa and a sensitizer for the antiproliferative effects of IFNα2.

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MEG3 Long Noncoding RNA Contributes to the Epigenetic Regulation of Epithelial-Mesenchymal Transition in Lung Cancer Cell Lines

Journal of Biological Chemistry ◽

10.1074/jbc.m116.750950 ◽

2016 ◽

Vol 292 (1) ◽

pp. 82-99 ◽

Cited By ~ 94

Author(s):

Minoru Terashima ◽

Shoichiro Tange ◽

Akihiko Ishimura ◽

Takeshi Suzuki

Keyword(s):

Lung Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Epigenetic Regulation ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Epithelial Mesenchymal Transition ◽

Cancer Cell Lines ◽

Lung Cancer Cell ◽

Mesenchymal Transition

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The role of microRNA-21 in the onset and progression of cancer

Future Medicinal Chemistry ◽

10.4155/fmc-2021-0096 ◽

2021 ◽

Author(s):

Ashutosh Singh ◽

Ashutosh Kumar Singh ◽

Rajanish Giri ◽

Dhruv Kumar ◽

Rohit Sharma ◽

...

Keyword(s):

Cancer Detection ◽

Tumor Suppressor Genes ◽

Noncoding Rna ◽

Early Cancer ◽

Cancer Resistance ◽

Aberrant Expression ◽

Small Noncoding Rna ◽

Expression Of Genes ◽

Oncogenic Property

MicroRNAs (miRNAs), a class of small noncoding RNA, posttranscriptionally regulate the expression of genes. Aberrant expression of miRNA is reported in various types of cancer. Since the first report of oncomiR-21 involvement in the glioma, its upregulation was reported in multiple cancers and was allied with high oncogenic property. In addition to the downregulation of tumor suppressor genes, the miR-21 is also associated with cancer resistance to various chemotherapy. The recent research is appraising miR-21 as a promising cancer target and biomarker for early cancer detection. In this review, we briefly explain the biogenesis and regulation of miR-21 in cancer cells. Additionally, the review features the assorted genes/pathways regulated by the miR-21 in various cancer and cancer stem cells.

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THU0078 EXPRESSION PROFILE ANALYSIS OF LONG NONCODING RNAS INDUCED BY IL-1ß IN RHEUMATOID ARTHRITIS FIBROBLAST-LIKE SYNOVIOCYTES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3072 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 251.1-251

Author(s):

J. M. Kim ◽

H. J. Kang ◽

S. J. Jung ◽

B. W. Song ◽

H. J. Jeong ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Expression Profile ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Aberrant Expression ◽

Iκb Kinase ◽

Ngs Data ◽

Fibroblast Like Synoviocytes

Background:Long noncoding RNAs (lncRNAs) have recently emerged as important biological regulators and the aberrant expression of lncRNAs has been reported in various diseases including cancer, cardiovascular disease, and diabetes mellitus. However, the role of lncRNAs in the pathogenesis of rheumatoid arthritis (RA) remains unknown.Objectives:Thus, we studied lncRNAs influenced by IL-1, which is one of the key mediators in the pathogenesis of RA, and also investigated whether regulation of NF-κB activation, which is known to be induced by IL-1, could lead to the changes of expression of those lncRNAs.Methods:Fibroblast-like synoviocytes (FLS) were obtained from the knee joints of the patients with RA. The next-generation sequencing (NGS) data were analyzed to identify differentially expressed lncRNAs between unstimulated RA FLS and IL-1-stimulated RA FLS. The expression levels of the top 5 candidates in NGS data were validated by RT-qPCR using extended number of unstimulated RA FLS and IL-1-stimulated RA FLS. IMD-0560, an inhibitor of IκB kinase (IKK) was used for the regulation of NF-κB activation. Activation and inhibition of NF-κB were confirmed by Western blotting. Changed expressions of the lncRNAs were identified by RT-qPCR.Results:NGS analysis revealed up-regulated 30 lncRNAs and down-regulated 15 lncRNAs in IL-1-treated RA FLS compared with unstimulated RA FLS. Top 5 lncRNAs were selected among 30 lncRNAs up-regulated by IL-1 in RA FLS based on fold-change with P-value cutoff. The up-regulated lncRNAs including NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 were validated by RT-qPCR. IMD-0560 inhibited phosphorylation of IκBα induced by IL-1 in RA FLS. Overexpression of lncRNAs induced by IL-1 was also inhibited by IMD-0560 in RA FLS.Conclusion:Our study revealed that IL-1 increased the expression of NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 in RA FLS. In addition, the expression of these lncRNAs was regulated by inhibition of NF-κB activation. Thus, our data suggest that the lncRNAs might be involved in the pathogenesis of RA through NF-κB signaling pathway.References:[1]Long noncoding RNAs and human disease. Trends Cell Biol. 2011 Jun;21(6):354-61.[2]A long noncoding RNA mediates both activation and repression of immune response genes. Science. 2013 Aug 16;341(6147):789-92.[3]Long noncoding RNA expression profile in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Res Ther. 2016 Oct 6;18(1):227.Disclosure of Interests:None declared

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