Overexpression of miR-23b-3b+miR-218-5p+miR-124-3p differentially modifies the transcriptome of C-33A and CaSki cells and the regulation of cellular processes involved in the progression of cervical cancer
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PROVIDER: PRJNA1225309 | ENA |
REPOSITORIES: ENA
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Project description:Dysregulation of tumor suppressor miRNAs (tsmiRs) is associated with tumor progression in cancer. miR-23b-3p, miR-218-5p and miR-124-3p are tsmiRs in cervical cancer (CC) and regulate the translation of genes involved in metastasis-related biological processes. Objective. To analyze transcriptome changes in cervical cancer cell lines (C-33A HPV-negative and CaSki HPV-positive) overexpressing miR-23b-3b+miR-218-5p+miR-124-3p, to identify specific target transcripts common to all three miRNAs, as well as signaling pathways and cellular processes related to tumor progression. Methods. The transcriptome of C-33A and CaSki cells transfected with miR-23b-3b+miR-218-5p+miR-124-3p was analyzed by RNA-seq. Differentially expressed genes (DEGs) were subjected to Gene Ontology analysis on the DAVID platform. The function of under-regulated genes was analyzed on the GEPIA 2.0, Kaplan-Meier plotter and STRING platforms. On the TargetScanHuman platform it was determined which transcripts have MREs for miR-23b-3p, miR-218-5p and/or miR-124-3p in their 3`UTR region. Results. Simultaneous overexpression of miR-218-5p, miR-124-3p and miR-23b-3p induced changes in global gene expression in C-33A and CaSki cells. In C-33A cells, DEGs included 45 over- and 172 under-regulated transcripts; in CaSki, 125 transcripts were over- and 84 under-regulated. The under-regulated transcripts enrich proliferation, migration, apoptosis and angiogenesis; 20 of these genes are associated with overall survival (OS) in women with CC, and 18 of the 20 mRNAs have MREs for one, two or all three miRNAs. Conclusions. miR-23b-3b+miR-218-5p+miR-124-3p, differentially modify global gene expression in C-33A and CaSki cells. The results indicate that these miRNAs act synergistically and modulate CC progression through individual and shared targets by two or all three miRNAs.
2025-02-24 | GSE289927 | GEO
Project description:Aberrant expression of oncomicroRNAs and tumor suppressor miRNAs (tsmiRs) contributes to the carcinogenesis and progression of cervical cancer (CC). miR-124-3p, miR-23b-3p, and miR-218-5p are tsmiRs that modulate oncogenes regulating cellular processes implicated in CC progression. This research aimed to explore transcriptomic changes in C-33A and CaSki cells following the overexpression of miR-124-3p, miR-23b-3p, and miR-218-5p, and to identify the biological processes (BPs) and pathways modulated by differentially expressed genes (DEGs). A total of 100 nM of miR-124-3p, miR-23b-3p, and miR-218-5p mimetics were transfected into C-33A and CaSki cells, and transcriptome changes were analyzed using RNA-seq. The Galaxy and R-Studio platforms were employed to identify DEGs, while BPs and pathways regulated by DEGs were identified through the DAVID platform. Transcriptional changes revealed both differences and similarities between cell lines and miRNAs. In C-33A cells, miR-124-3p and miR-218 regulated direct and indirect targets involved in the cell cycle and apoptosis. In CaSki cells, apoptosis and viral carcinogenesis were regulated by genes modulated directly or indirectly by miR-124-3p and miR-23b-3p. These tsmiRs demonstrated synergistic activity, regulating multiple transcripts that modulate processes and pathways involved in CC progression, with or without HPV. These findings suggest that miR-124-3p, miR-23b-3p, and miR-218-5p may represent promising therapeutic alternatives for CC treatment.
2024-11-13 | GSE279412 | GEO
Project description:Differentially Expressed Genes in C-33A and CaSki Cells Overexpressing miR-124-3p, miR-23b-3p, or miR-218-5p Modulate Processes and Pathways Involved in Cervical Cancer Progression
| PRJNA1172670 | ENA
Project description:This study tested candidate therapeutic antimiRs in a comprehensive new collection of primary myoblasts derived from myotonic dystrophy type 1 (DM1) patients. DM1 is caused by genetically unstable CTG repeat expansions in the DMPK gene and has multiple clinical presentations, likely because of variable repeat sizes at the tissue and organ levels. Expanded DMPK transcripts deplete Muscleblind-Like Splicing Regulator protein MBNL1, which in turn causes DM1 symptoms. A promising therapeutic approach increases the expression of MBNL1 by blocking natural repressors miR-23b and miR-218 employing antimiRs with chemical modifications designed for a better pharmacological profile in humans. In untreated primary cells, we demonstrate that upregulated therapeutic targets miR-23b and miR-218 and reduced MBNL1 protein levels inversely correlate with CTG repeat size, supporting that active MBNL1 protein repression synergizes with the sequestration by CUG repeats in DM1. Upon treatment with novel antimiRs, multiple readouts of RNA toxicity associated with typical DM1 alterations improved. MBNL1-dependent exon inclusions, and myoblast fusion and myotube area defects, showed robust correction over a wide range of CTG expansions. Unexpectedly, antimiR treatment also reduced DMPK transcript levels and the number of ribonuclear aggregates. Based on these data, we selected a leading antimiR for further transcriptomics characterization and demonstrated that it reversed up to 68% of dysregulated genes. The study revealed that the candidate antimiRs could provide therapy to clinically relevant DM1 forms over a wide range of repeat sizes and genetic backgrounds by simultaneously reducing MBNL1 sequestration and derepressing protein synthesis.
2024-05-01 | GSE237411 | GEO
Project description:Receptor tyrosine kinase pathway signalings plays a central role in the growth and progression of glioblastoma, a highly aggressive group of brain tumors. We recently reported that miR-218 repression, an essentially uniform feature of human GBM, directly promotes RTK hyperactivation by increasing the expression of key positive signaling effectors, including EGFR, PLCr1, PIK3CA and ARAF. However, enhanced RTK signaling is known to activate compensatory inhibitory feedback mechanisms in both normal and cancer cells. We demonstrate here that miR-218 repression in GBM cells also increases the abundance of additional up stream and downstream signaling mediators, including PDGFRa, RSK2, and S6K1, which collectively funciton to alleviate inhibitory RTK feedback regulation. In turn, RTK signaling suppresses miR-218 expression via STAT3, which binds to the miR-218 locus, along with BCLAF1, to repress its expression. These data identify novel interacting feedback loops by which miR-218 repression promotes increased RTK signaling in high-grade gliomas.
2022-03-01 | PXD002112 | Pride
Project description:In this study, we aimed to investigate the functional roles of miR-33a in PCa.We investigated the relative miR-33a level in normal and tumor prostate samples as well as PCa cell lines. Then, we performed a detailed functional analysis of mir-33a in LNCaP and VCaP PCa cells and evaluated proliferative, invasive and anchorage independent growth potential of cells upon overexpression and knockdown of miR-33a. We next explored the potential direct targets of miR-33a in PCa cells via utilizing gene expression microarray analysis, bioinformatics search, further qRT-PCR, western blot, and luciferase assay confirmation. Our results demonstrated that miR-33a is significantly downregulated in PCa tumor samples and PCa cell lines, pointing its tumor suppressor potential in PCa. Overexpression and knockdown of miR-33a significantly altered the proliferative, invasive and anchorage independent growth potentials of cells through altering the expression of its direct target PIM1. Ectopic induction of MiR-33a expression reversed the impacts of PIM1 overexpression on cellular phenotypes associated with PCa progression. Our results suggest that mir-33a exerts its tumor suppressor potential through targeting its direct target PIM1 and carries crucial roles in PCa tumorigenesis.
2017-10-31 | GSE89034 | GEO
Project description:MiR-33a is involved in the maintenance of Glioma Initiating Cells (GIC) and tumor progression. MicroRNA-33a could promote GIC growth and self-renewal by regulating two pathways including cAMP/PKA pathway and Notch pathway. We used microarrays to identify the direct target genes of miR-33a in a glioblastoma cell line D456MG. We used microarrays to detail the global change of gene expression after miR-33a over-expression and identified target genes during this process.
2014-07-17 | GSE59484 | GEO
Project description:Analysis of genes regulated by miR-23b/-27b overexpression in aggressive PC3-ML cells, confirmed by antagomiR inhibition of miR-23b and miR-27b in the relatively indolent cell line LNCaP. Genes that were downregulated in PC3-ML overexpression and upregulated with LNCaP inhibition were further explored as downstream targets of miR-23b/-27b.
2016-02-10 | GSE76620 | GEO
Project description:MiR-33a is involved in the maintenance of Glioma Initiating Cells (GIC) and tumor progression. MicroRNA-33a could promote GIC growth and self-renewal by regulating two pathways including cAMP/PKA pathway and Notch pathway. We used microarrays to identify the direct target genes of miR-33a in a glioblastoma cell line D456MG. We used microarrays to detail the global change of gene expression after miR-33a over-expression and identified target genes during this process. Cells were infected with lenti-virus expressing a control vector (pWPXLD) or human primary miR-33a. Then RNA was extracted and gene expression was profiled by Affymetrix microarray.
2014-07-17 | E-GEOD-59484 | biostudies-arrayexpress
Project description:Analysis of genes regulated by miR-23b/-27b overexpression in aggressive PC3-ML cells, confirmed by antagomiR inhibition of miR-23b and miR-27b in the relatively indolent cell line LNCaP. Genes that were downregulated in PC3-ML overexpression and upregulated with LNCaP inhibition were further explored as downstream targets of miR-23b/-27b. PC3-Ml cells were transduced with miR-23b/-27b or a scrambled miRNA control, and only cells expressing greater than 95% transduction efficiency were used for array. LNCaP cells were transfected with antagomiRs to miR-23b and miR-27b, or a non-coding control.
2016-02-10 | E-GEOD-76620 | biostudies-arrayexpress