LINC01088 inhibits tumorigenesis of ovarian epithelial cells by targeting miR-24-1-5p

Zhang, Weijiang; Jing, Fei; Yu, Shuqian; Shen, Jiayu; Zhu, Xiaojuan; Sadhukhan, Annapurna; Lü, Weiguo; Zhou, Jianwei

doi:10.1038/s41598-018-21164-9

“…The role of miR‐183‐5p in EC needs to be further elucidated. Additionally, miR‐24‐1‐5p could act as an oncogene that facilitates the proliferation of ovarian epithelial cells, which is contrary to our findings. The functional differences in the role of the same miRNA in different cancers might be due to tissue specificity.…”

Section: Discussioncontrasting

confidence: 99%

Novel miRNA markers for the diagnosis and prognosis of endometrial cancer

Wang

¹

,

Xu

²

,

Yu

³

et al. 2020

J Cellular Molecular Medi

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Endometrial cancer (EC), one of most common gynaecological malignant tumours, threatens the female health worldwide, especially in developed countries. 1 According to estimated data, more than 63 230 new EC cases and 11 350 EC deaths are projected to occur in the United States in 2018. 2 Current diagnoses for uterine corpus tumours mainly depend on clinical and histological features.However, 15%-20% of these tumours still have a high risk of recurrence and even further deterioration. Although some molecular AbstractAs endometrial cancer (EC) is a major threat to female health worldwide, the ability to provide an accurate diagnosis and prognosis of EC is promising to improve its treatment guidance. Since the discovery of miRNAs, it has been realized that miRNAs are associated with every cell function, including malignant transformation and metastasis. This study aimed to explore diagnostic and prognostic miRNA markers of EC.In this study, differential analysis and machine learning were performed, followed by correlation analysis of miRNA-mRNA based on the miRNA and mRNA expression data. Nine miRNAs were identified as diagnostic markers, and a diagnostic classifier was established to distinguish between EC and normal endometrium tissue with overall correct rates >95%. Five specific prognostic miRNA markers were selected to construct a prognostic model, which was confirmed more effective in identifying EC patients at high risk of mortality compared with the FIGO staging system. This study demonstrates that the expression patterns of miRNAs may hold promise for becoming diagnostic and prognostic biomarkers and novel therapeutic targets for EC. K E Y W O R D S diagnostic classifier, endometrial cancer, microRNA, molecular biomarker, prognostic model S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Wang Q, Xu K, Tong Y, et al. Novel miRNA markers for the diagnosis and prognosis of endometrial cancer. J Cell Mol Med. 2020;24:4533-4546. https://doi.

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“…The commonly up-regulated coding genes were TRPM4 (Transient Receptor Potential Cation Channel subfamily M member 4), PPBP (Pro-Platelet Basic Protein), MAGEB2 (MAGE family member B2), CREB5 (cAMP Responsive Element Binding Protein 5), and GCNA (Germ Cell Nuclear Acidic Peptidase). The noncoding gene LINC01088 found to be up-regulated in all four cell lines was recently implicated as a tumor suppressor found in reduced levels in ovarian tumors and acts by targeting miR-24-1-5p-mediated regulation of PAK4 expression (21). Despite the unique gene regulation in each cell line, functional-level analysis with GSEA showed several common pathways regulated by AZA in all four cell lines ( Fig.…”

Section: Resultsmentioning

confidence: 84%

Multiomics of azacitidine-treated AML cells reveals variable and convergent targets that remodel the cell-surface proteome

Leung

¹

,

Nguyen²,

Shi

³

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are diseases of abnormal hematopoietic differentiation with aberrant epigenetic alterations. Azacitidine (AZA) is a DNA methyltransferase inhibitor widely used to treat MDS and AML, yet the impact of AZA on the cell-surface proteome has not been defined. To identify potential therapeutic targets for use in combination with AZA in AML patients, we investigated the effects of AZA treatment on four AML cell lines representing different stages of differentiation. The effect of AZA treatment on these cell lines was characterized at three levels: the DNA methylome, the transcriptome, and the cell-surface proteome. Untreated AML cell lines showed substantial overlap at all three omics levels; however, while AZA treatment globally reduced DNA methylation in all cell lines, changes in the transcriptome and surface proteome were subtle and differed among the cell lines. Transcriptome analysis identified five commonly up-regulated coding genes upon AZA treatment in all four cell lines, TRPM4 being the only gene encoding a surface protein, and surface proteome analysis found no commonly regulated proteins. Gene set enrichment analysis of differentially regulated RNA and surface proteins showed a decrease in metabolic pathways and an increase in immune defense response pathways. As such, AZA treatment led to diverse effects at the individual gene and protein levels but converged to common responses at the pathway level. Given the heterogeneous responses in the four cell lines, we discuss potential therapeutic strategies for AML in combination with AZA.AML | azacitidine | target discovery | multiomics | surface proteomics M yelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematopoietic malignancies that are genetically and epigenetically diverse in nature. As myeloid lineage cells differentiate from their hematopoietic stem/progenitor cells, aberrant epigenetic changes can occur at any differentiation stage, driving cells into cancerous phenotypes (1). As such, AML is routinely classified according to hematopoietic lineages by cell morphology or by cytometry using sparse surface markers (2, 3). Among many epigenetic changes that occur in MDS and AML, the best-characterized change is the DNA methylation of cytosine bases in CpG islands (4). In fact, a hallmark of epigenetic changes in AML is the redistribution of methylated CpG dinucleotides with loss of methylation across intergenic regions, primarily transposable elements and repeats, and gain of aberrant methylation near the promoters of a number of genes, including well-known tumor suppressors such as p16INK4a (5). As such, it is believed that these diseases are more sensitive to hypomethylating agents such as DNA methyltransferase inhibitors (DMNTi) (6, 7). One such DMNTi, azacitidine (AZA), has been efficaciously used for over a decade to treat MDS and AML (8,9). At high doses, AZA induces rapid DNA damage and is cytotoxic; at lower doses, AZA induces DNA hypomethylation by covalent trappi...

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“…The commonly up-regulated coding genes were TRPM4 (Transient Receptor Potential Cation Channel subfamily M member 4), PPBP (Pro-Platelet Basic Protein), MAGEB2 (MAGE family member B2), CREB5 (cAMP Responsive Element Binding Protein 5), and GCNA (Germ Cell Nuclear Acidic Peptidase). The non-coding gene LINC01088 found to be up-regulated in all four cell lines was recently implicated as a tumor suppressor found in reduced levels in ovarian tumors and acts by targeting miR-24-1-5p mediated regulation PAK4 expression (25) . Despite the unique gene regulation in each cell line, functional level analysis with GSEA showed several common pathways regulated by AZA in all four cell lines (Figure 2E, Supplemental Figure 6A-B).…”

Section: Transcriptome In Aml Cell Lines and Its Regulation By Azacitmentioning

confidence: 95%

“…Through combining the significance of gene regulation at both methylation and transcription levels and applying the joint scores onto a gene interaction network, this algorithm increases analysis power in identifying subnetworks of dysregulated genes with collateral information. Through this analysis, each AML cell line had [16][17][18][19][20][21][22][23][24][25][26][27] functional modules identified and these functional modules encompass 481 ~ 612 genes (Supplemental Table 5). In particular, analysis of the KG1a cell line benefited most from SMITE, where 528 genes were found to be dysregulated compared to 160 genes when analyzed using transcription data alone.…”

Section: Comparisons Of Methylome Transcriptome and Surface Proteommentioning

confidence: 99%

Multi-omics analysis of AML cells treated with azacitidine reveals highly variable cell surface proteome remodeling

Leung

¹

,

Nguyen²,

Shi³

et al. 2018

Preprint

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Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are diseases of abnormal hematopoietic differentiation with aberrant epigenetic alterations. Azacitidine (AZA) is a DNA methyltransferase inhibitor (DNMTi) widely used to treat MDS and AML, yet the impact of AZA on the cell surface proteome has not been defined. To identify potential therapeutic targets for use in combination with AZA in AML patients, we investigated the effects of AZA treatment on four AML cell lines (KG1a, HL60, HNT34, and AML193), representing different stages of differentiation. The effect of AZA treatment on these cell lines was characterized at three levels: the DNA methylome (methylation array), the transcriptome (gene expression array), and the cell surface proteome (glycoprotein capture with SILAC labeling). Untreated AML cell lines showed substantial overlap in their methylomes, transcriptomes, and cell surface proteomes. AZA treatment globally reduced DNA methylation in all cell lines, but changes in the transcriptome and surface proteome were subtle and differed among the cell lines. Transcriptome analysis identified five commonly upregulated coding genes upon AZA treatment in all four cell lines, TRPM4 being the only gene encoding a surface protein, and surface proteomics analysis found no commonly regulated proteins. Gene Set Enrichment Analysis (GSEA) of differentially-regulated RNA and surface proteins showed a decrease in metabolism pathways and an increase in immune defense response pathways. As such, AZA treatment in four AML cell lines had diverse effects at the individual gene and protein level, but converged to regulation of metabolism and immune response at the pathway level. Given the heterogeneous response of AZA in the four cell lines at the gene and protein level, we discuss potential therapeutic strategies for combinations with AZA.

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LINC01088 inhibits tumorigenesis of ovarian epithelial cells by targeting miR-24-1-5p

Cited by 26 publications

References 46 publications

Novel miRNA markers for the diagnosis and prognosis of endometrial cancer

Novel miRNA markers for the diagnosis and prognosis of endometrial cancer

Multiomics of azacitidine-treated AML cells reveals variable and convergent targets that remodel the cell-surface proteome

Multi-omics analysis of AML cells treated with azacitidine reveals highly variable cell surface proteome remodeling

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