IL-2RG as a possible immunotherapeutic target in CRC predicting poor prognosis and regulated by miR-7-5p and miR-26b-5p

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Май 8, 2024

Abstract Despite advances in treatment strategies, colorectal cancer (CRC) continues to cause significant morbidity and mortality, with mounting evidence a close link between immune system dysfunctions issued. Interleukin-2 receptor gamma (IL-2RG) plays pivotal role as common subunit the IL-2 family cytokines activates JAK-STAT pathway. This study delves into of within tumor microenvironment investigates potential microRNAs (miRNAs) that directly inhibit IL-2RG, aiming discern their impact on CRC clinical outcomes. Bioinformatics analysis revealed upregulation IL-2RG mRNA TCGA-COAD samples showed strong correlations infiltration various lymphocytes. Single-cell corroborated these findings, highlighting expression critical cell subsets. To explore miRNA involvement dysregulation, was isolated from tissues lymphocytes 258 patients 30 healthy controls, cloned pcDNA3.1/CT-GFP-TOPO vector. Human embryonic kidney lines (HEK-293T) were transfected this construct. Our research involved comprehensive miRPathDB, miRWalk, Targetscan databases identify miRNAs associated 3′ UTR human IL-2RG. The microRNA (miRNA) molecules, hsa-miR-7-5p hsa-miR-26b-5p, have been identified potent suppressors patients. Specifically, downregulation hsa-miR-26b-5p has shown result Prognostic evaluation hsa-miR-7-5p, using data patient samples, established higher lower both poorer Additionally, several long non-coding RNAs (LncRNAs), such ZFAS1, SOX21-AS1, SNHG11, SNHG16, SNHG1, DLX6-AS1, GAS5, SNHG6, MALAT1, which may act competing endogenous RNA molecules for IL2RG by sequestering shared hsa-miR-26b-5p. In summary, investigation underscores utility serum tissue biomarkers predicting prognosis while also offering promise targets immunotherapy management. Graphical

Язык: Английский

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The potential relevance of long non-coding RNAs in colorectal cancer pathogenesis and treatment: A review focus on signaling pathways

Pathology - Research and Practice, Год журнала: 2023, Номер 253, С. 155044 - 155044

Опубликована: Дек. 20, 2023

Язык: Английский

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Deciphering the oncogenic network: how C1QTNF1-AS1 modulates osteosarcoma through miR-34a-5p and glycolytic pathways

Frontiers in Oncology, Год журнала: 2025, Номер 14

Опубликована: Янв. 9, 2025

Osteosarcoma (OS), a prevalent metastatic cancer among young individuals, is associated with grim prognosis. Long non-coding RNAs (lncRNAs), including C1QTNF1-AS1, are pivotal regulators of cell proliferation and motility. As an oncogene, C1QTNF1-AS1 implicated in various tumor types, such as colorectal, pancreatic, hepatocellular carcinomas, OS. The aim this study was to investigate the functions underlying mechanisms progression osteosarcoma. This investigation focused on elucidating functional roles OS cells. Bioinformatics tools were utilized identify interaction between microRNA miR-34a-5p well targeting LDHA PDK3 by miR-34a-5p. Dual-luciferase reporter assays RNA immunoprecipitation employed validate these interactions. Expression profiles miR-34a-5p, LDHA, osteosarcoma cells analyzed using RT-PCR western blot analyses, revealing their intricate relationships. impact molecules proliferation, invasion, migration assessed through CCK-8, Transwell, Cell scratch assay. Moreover, effects aerobic glycolysis examined quantifying ATP levels, lactate production, glucose uptake capacity, extracellular acidification rate. findings indicated significant decrease expression levels compared normal osteoblasts. A parallel downregulation trend also observed Silencing led marked upregulation cells, which partially attenuated mimics. Functional evaluations demonstrated that suppression accelerated growth, motility, invasiveness, Warburg effect. Conversely, overexpression mitigated stimulatory effects, suggesting regulatory role modulating progression. Our research emphasizes critical pathogenesis (OS). We discovered indirectly upregulates suppressing regulator cascade events promotes enhancing glycolytic metabolism supplying energy for migration, invasion. These suggest potential therapeutic target highlight importance understanding network involving lncRNAs

Язык: Английский

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CircRNAs in Colorectal Cancer: Unveiling Their Roles and Exploring Therapeutic Potential

Biochemical Genetics, Год журнала: 2025, Номер unknown

Опубликована: Март 3, 2025

Язык: Английский

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LINC01559: roles, mechanisms, and clinical implications in human cancers

Human Cell, Год журнала: 2025, Номер 38(3)

Опубликована: Апрель 9, 2025

Язык: Английский

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Identification of dysregulated competitive endogenous RNA network driven by copy number variation in colon adenocarcinoma

Computer Methods in Biomechanics & Biomedical Engineering, Год журнала: 2025, Номер unknown, С. 1 - 12

Опубликована: Май 13, 2025

Competitive endogenous RNA (ceRNA) network modulation plays a crucial role in pathogenesis of colon adenocarcinoma (COAD). This study analyzed The Cancer Genome Atlas(TCGA) data to identify 151 copy number variation (CNV)-driven lncRNAs COAD, constructing ceRNA (6 lncRNAs-14 miRNAs-68 mRNAs). Functional enrichment revealed their roles muscle system processes , blood vessel development and extracellular matrix organization. Survival analysis linked LINC00941 amplification poor prognosis. Two CNV-driven lncRNA-targeting drugs were identified, offering insights into COAD mechanisms potential biomarkers.

Язык: Английский

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miRNA, lncRNA and circRNA: targeted molecules with therapeutic promises in Mycoplasma pneumoniae infection

Archives of Microbiology, Год журнала: 2023, Номер 205(8)

Опубликована: Июль 21, 2023

Язык: Английский

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Dynamic relationship between the aryl hydrocarbon receptor and long noncoding RNA balances cellular and toxicological responses

Biochemical Pharmacology, Год журнала: 2023, Номер 216, С. 115745 - 115745

Опубликована: Авг. 17, 2023

Язык: Английский

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Circ_0001944 Targets the miR-1292-5p/FBLN2 Axis to Facilitate Sorafenib Resistance in Hepatocellular Carcinoma by Impeding Ferroptosis

ImmunoTargets and Therapy, Год журнала: 2024, Номер Volume 13, С. 643 - 659

Опубликована: Ноя. 1, 2024

Sorafenib, an orally active potent tyrosine kinase inhibitor (TKI), represented a primary treatment in patients with advanced hepatocellular carcinoma (HCC). Unfortunately, sorafenib resistance was regarded as huge obstacle for HCC treatment. RNA-sequencing including circRNA Sequencing (circRNA-Seq) circular RNAs (circRNAs), miRNA (miRNA-Seq) microRNAs (miRNAs), well mRNA (mRNA-Seq) mRNAs sorafenib-resistant cells vs sorafenib-sensitive cells, were performed. Then, interaction correlation analysis between differentially expressed circRNAs and miRNAs their target genes Huh7/SOR SMMC7721/SOR exhibited. The "circRNA-miRNA-mRNA" network constructed through the Cytoscape software application, Circular RNA Interactome Targetscan prediction, binding protein immunoprecipitation (RIP), pull-down, Dual luciferase reporter assay. Furthermore, mRNA-Seq, Gene Ontology (GO) function Kyoto Encyclopedia of Genes Genomes (KEGG) pathway enrichment downstream involved implemented. Iron detection assay, Lipid peroxidation quantification ROS measurement CCK-8 tumor challenge vivo used to determine mechanisms promoting HCC, where is clearly in. circ_0001944 circ_0078607 upregulation 2 downregulated (circ_0002874 circ_0069981), 11 upregulated miR-193a-5p, miR-197-3p, miR-27a-5p, miR-551b-5p, miR-335-3p, miR-767-3p, miR-767-5p, miR-92a-1-5p, miR-92a-3p, miR-3940-3p, miR-664b-3p 3 (miR-1292-5p, let-7c-5p, miR-99a-5p) determined. Among these non-coding (ncRNAs), miR-1292-5p should not be drop out sight; has been proved inhibit its expression HCC. Subsequent findings also raise that directly targeted 3'-noncoding region (3'-UTR) Fibulin (FBLN2) mRNA. targets miR-1292-5p/FBLN2 axis cell ferroptosis which indicated regulators associated iron overload lipid "rearranged". Most importantly, mitigating ferroptosis, cannot left unrecognized. Circ_0001944 putative reversing Our are expected provide new directions sensitization

Язык: Английский

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LINC02257 regulates malignant phenotypes of colorectal cancer via interacting with miR-1273g-3p and YB1

Cell Death and Disease, Год журнала: 2024, Номер 15(12)

Опубликована: Дек. 18, 2024

Abstract Colorectal cancer (CRC) is the third most common diagnosed and second leading cause of cancer-related deaths. Emerging evidence has indicated that long non-coding RNAs (lncRNAs) are involved in progression various types cancer. In this study, we aimed to identify potential causal lncRNAs CRC through comprehensive multilevel bioinformatics analyses, coupled with functional validation. Our analyses identified LINC02257 as being highly expressed CRC, associated poor survival advanced tumor stages among patients CRC. Genome-wide association analysis revealed significant associations between variants near suggesting a role for Network playing key epithelial-mesenchymal transition pathway. Single-cell RNA sequencing showed elevated expression was reduced proportion epithelial cells. vitro experiments positively regulated metastatic proliferative Mechanistically, affected malignancy by functioning competitive endogenous microRNAs RNA-binding proteins. upregulated SERPINE1 sequestering suppressive miR-1273g-3p, thereby increasing abilities Additionally, directly interacted YB1 induced its phosphorylation, facilitating nuclear translocation. The transcriptional activation target genes oncogenic functions . Taken together, our results demonstrate promising therapeutic treatment.

Язык: Английский

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