MiR-223-3p and miR-29a-3p induced transcriptional rewiring in lung adenocarcinoma cell lines
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ABSTRACT:
PROVIDER: PRJNA1130031 | ENA |
REPOSITORIES: ENA
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Project description:We investigated the biomolecular activity of miR-29a-3p/miR-223-3p in human lung adenocarcinoma (LUAD) by performing transcriptome profiling of H2023 (LUAD) cell line upon modulation of miR-29a-3p/miR-223-3p by mimic (QIAGEN) (OE) or antisense microRNA (KD).
2025-05-29 | GSE271130 | GEO
Project description:Preeclampsia (PE) is a major cause of maternal and fetal morbidity and mortality during pregnancy. PE is characterized by widespread endothelial dysfunction in mothers and fetuses. To date, the etiology of PE remains elusive, but the dysregulation of microRNAs (miRNAs) in endothelial cells may contribute to the pathogenesis of PE. We have reported that PE downregulates expression of two miRNAs, miR-29a-3p and miR-29c-3p (miR-29a/c-3p) and knockdown of miR-29a/c-3p impairs functions of human umbilical vein endothelial cells (HUVECs). Herein, we tested the hypothesis that knockdown of miR-29a/c-3p sex-specifically impairs cellular responses to vascular endothelial growth factor-A (VEGFA) and fibroblast growth factor 2 (FGF2) accompanying with disrupted transcriptome in HUVECs. MiR-29a/c-3p were downregulated using miR-29c-3p inhibitors in HUVECs, followed by assessing chemotactic and proliferative responses to VEGFA and FGF2. RNA-seq analysis was conducted to profile transcriptomic changes. Compared with negative control, miR-29c-3p inhibitors suppressed over 90% of miR-29a/c-3p in HUVECs at 48 h. MiR-29c-3p inhibitors decreased VEGFA-stimulated chemotaxis by 25% in male, but not female HUVECs. MiR-29c-3p inhibitors did not alter FGF2-stimulated chemotaxis or VEGFA- and FGF2-stimulated proliferation in HUVECs. RNA-seq revealed that miR-29a/c-3p inhibitors differentially altered the transcriptome between female and male HUVECs. Functional enrichment analyses showed that miR-29a/c-3p-regulated genes were differently associated with hypertension, heart, angiogenesis, and immunology in female and male HUVECs. These data demonstrate that knockdown of miR-29a/c-3p differentially affects cellular responses to angiogenic factors in female and male HUVECs, in association with disrupted transcriptome. These miR-29a/c-3p-regulated genes might serve as sex-specific therapeutic targets for PE-associated vascular dysfunction.
2026-05-28 | GSE310550 | GEO
Project description:Obesity during pregnancy is linked to a high risk of offspring overweight, insulin resistance, type 2 diabetes, and cardiometabolic disease in later life. However, the underlying mechanisms by which maternal factors drive these long-lasting effects remain to be fully elucidated. In our study, we have demonstrated that in diet-induced-obesity (DIO) pregnant mice, maternal small extracellular vesicles (sEV) in circulating system have the ability to cross the placental barrier and reach the liver of fetal mice, exerting a sustained adverse impact on offspring insulin sensitivity. Further investigations have revealed that pathogenically increased miR-29a-3p in maternal sEV from DIO mice can be delivered into livers of fetal offspring. Elevated miR-29a-3p subsequently alter epigenetic state in fetal liver via targeting several key methyltransferases and demethylases, interrupting the DNA methylation landscape, including hypomethylation of PGC-1α. Such epigenetic remodeling abnormally promotes early hepatic gluconeogenesis at fetal stage that contribute to the adult metabolic disturbance in offspring. Taken together, our finding suggests that the transplacental delivery of maternal sEV could serve as a potential mechanism for prenatal programming of metabolic health in offspring.
2026-07-31 | GSE299405 | GEO
Project description:MiRNA-146a-5p, and -29-3p are repeatedly reported to be dysregulated in wound healing, however, not much is known about their roles in in the immune inflammatory responses and skin regeneration within cellular networks. We tested our hypothesis that suppressing the two over-expressed miRNAs would address wound healing impairments, using two distinct models of wound healing: Immortalised keratinocytes (HaCaT cells) transfected with LNA (locked nucleic acid)-spiked fully phosphorothioate modified antisense miR-146a-5p (5’-TGgaauucAgTuCucA-3’), miR-29a-3p (5’-AuuTcaGauGguGcuA-3’) oligos (LNA bases are written in capital letters while 2′-O-methyl RNA bases in small letters) and a scramble (Scr) control oligo (5’-CaaTagGguCaaGauT-3’) individually or in combination, and STZ induced type 1 diabetes animal model of wound healing. We observed significant corrections of dysfunctional cell migration (p<0.01 on day 8; and p<0.05 on day 9), decreased inflammation at day 3 (p<0.01) and day 10 (p<0.0001), reduction of excessive production of reactive oxygen species (p<0.01) 3 days post-wounding while increasing the density of blood vessel networks on day 3 (p<0.01) and day 10 (p<0.0001). This was consistent with cytoskeletal rearrangements and collagen alterations observed with proteome profiling. Our data suggest that synergetic potential of dual inhibition of the two miRNAs is a superior approach compared to individual miRNA inhibition, and a potential treatment for a multitude of wound healing impairments observed in diabetic wounds.
2025-12-15 | PXD060087 | Pride
Project description:The lung is one of the most common sites for cancer metastasis. Collagens in the lung provide a permissive microenvironment that supports the colonization and outgrowth of disseminated tumor cells. Therefore, down-regulating the production of collagens may contribute to the inhibition of lung metastasis. It has been suggested that miR-29 exhibits effective anti-fibrotic activity by negatively regulating the expression of collagens. Indeed, our clinical lung tumor data shows that miR-29a-3p expression negatively correlates with collagen I expression in lung tumors and positively correlates with patients’ outcomes. However, suitable carriers need to be selected to deliver this therapeutic miRNA to the lungs. In this study, we found that the chemotherapy drug cisplatin facilitated miR-29a-3p accumulation in the exosomes of lung tumor cells, and this type of exosomes exhibited a specific lung-targeting effect and promising collagen down-regulation. To scale up the preparation and simplify the delivery system, we designed a lung-targeting liposomal nanovesicle (by adjusting the molar ratio of DOTAP/cholesterol–miRNAs to 4:1) to carry miR-29a-3p and mimic the exosomes. This liposomal nanovesicle delivery system significantly down-regulated collagen I secretion by lung fibroblasts in vivo, thus alleviating the establishment of a pro- metastatic environment for circulating lung tumor cells.
2020-11-20 | GSE161832 | GEO
Project description:Obesity during pregnancy is linked to a high risk of offspring overweight, insulin resistance, type 2 diabetes, and cardiometabolic disease in later life. However, the underlying mechanisms by which maternal factors drive these long-lasting effects remain to be fully elucidated. In our study, we have demonstrated that in diet-induced-obesity (DIO) pregnant mice, maternal small extracellular vesicles (sEV) in circulating system have the ability to cross the placental barrier and reach the liver of fetal mice, exerting a sustained adverse impact on offspring insulin sensitivity. Further investigations have revealed that pathogenically increased miR-29a-3p in maternal sEV from DIO mice can be delivered into livers of fetal offspring. Elevated miR-29a-3p subsequently alter epigenetic state in fetal liver via targeting several key methyltransferases and demethylases, interrupting the DNA methylation landscape, including hypomethylation of PGC-1α. Such epigenetic remodeling abnormally promotes early hepatic gluconeogenesis at fetal stage that contribute to the adult metabolic disturbance in offspring. Taken together, our finding suggests that the transplacental delivery of maternal sEV could serve as a potential mechanism for prenatal programming of metabolic health in offspring.
2026-07-31 | GSE295756 | GEO
Project description:miR-493-5p, miR-3662, and miR-589-3p were estimated as working microRNAs in bleomycin- and methotrexate-induced phenotypic changes in A549 cells via microRNAs-Proteins Analysis of Integrative Relationship (miR-PAIR). To verify the effect of these miRNAs on the their target protein expression levels, comprehensive expression of proteins in A549 cells treated with miR-493-59, miR-3662, and miR-589-3p mimic was examined by SWATH-MS method. As expected by a miR-PAIR mehtod, almost target proteins were succesfully regulated by miR-493-5p and miR-589-3p mimics.
2025-07-25 | PXD053397 | Pride
Project description:Oxaliplatin (oxPt) resistance in colorectal cancers (CRC) is a major unsolved problem. Consequently, predictive markers and a better understanding of resistance mechanisms are urgently needed. To investigate if the recently identified predictive miR-625-3p is functionally involved in oxPt resistance, stable and inducible models of miR-625-3p dysregulation were analyzed. Ectopic expression of miR-625-3p in CRC cells led to increased resistance towards oxPt. The mitogen-activated protein kinase (MAPK) kinase 6 (MAP2K6/MKK6) – an activator of p38 MAPK - was identified as a functional target of miR-625-3p, and, in agreement, was down-regulated in patients not responding to oxPt therapy. The miR-625-3p resistance phenotype could be reversed by anti-miR-625-3p treatment and by ectopic expression of a miR-625-3p insensitive MAP2K6 variant. Transcriptome, proteome and phosphoproteome profiles revealed inactivation of MAP2K6-p38 signaling as a possible driving force behind oxPt resistance. We conclude that miR-625-3p induces oxPt resistance by abrogating MAP2K6-p38 regulated apoptosis and cell cycle control networks.
2017-03-29 | MSV000080762 | MassIVE
Project description:This is a prospective-retrospective study to determine if the expression of the miRNA’s miR-31-3p and miR-31-5p are prognostic of patient outcomes or predictive of the benefit from anti-EGFR therapy in stage III Colon Cancer. The present study will utilize FFPE tumor samples collected from patients enrolled in the PETACC-8 study conducted by the Fédération Francophone de Cancérologie Digestive (FFCD). This phase 3 clinical trial prospectively randomized fully resected stage III colon cancer patients to receive adjuvant treatment with either FOLFOX-4 plus cetuximab or FLOFOX-4 alone.
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Project description:miR-29a/b1 was reported to be involved in the regulation of reproductive function in female mice, but the underlying molecular mechanisms were not clear. In this study, female mice lacking miR-29a/b1 showed a delay in vaginal opening, irregular estrus cycles, ovulation disorder and infertility. However, the development of egg was normal in mutant mice and the ovulation disorder could be rescued by the superovulation treatment. The plasma level of luteinizing hormone (LH) was significantly lower in the mutant mice. Using iTRAQ coupled with LC-MS/MS, we found that the deficiency of miR-29a/b1 in mice resulted in an abnormal expression of a number of proteins involved in vesicular transport and secretion in the pituitary gland. The miR-29a/b1 targeting gene Dnmt3a and Hdac4 were up-regulated in the pituitary of miR-29a/b1 knockout mice suggesting that these two epigenetic writers may be the upstream causes for these phenotype changes due to miR-29a/b1 deficiency. These findings demonstrated that miR-29a/b1 is indispensable for the function of the reproductive axis through regulating LH secretion in the pituitary gland.
2021-09-09 | PXD017106 | Pride