Cancer-associated fibroblasts promote the stemness and progression of renal cell carcinoma via exosomal miR-181d-5p
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ABSTRACT:
PROVIDER: PRJNA880868 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21591462.fastq.gz | Fastqsanger.gz | |||
| SRR21591463.fastq.gz | Fastqsanger.gz | |||
| SRR21591464.fastq.gz | Fastqsanger.gz | |||
| SRR21591465.fastq.gz | Fastqsanger.gz | |||
| SRR21591466.fastq.gz | Fastqsanger.gz |
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Project description:The mechanisms underlying the effects of cancer-associated fibroblasts (CAFs) on cancer stemness and tumor progression in renal cell carcinoma (RCC) have not been elucidated yet. In the present study, we found that the enrichment of CAFs was positively associated with tumor progression and cancer stemness in RCC. Further investigation revealed that CAFs could enhance cancer stemness through delivering exosomes to RCC cells, and miR-181d-5p was identified as the critical exosomal miRNA in CAF secreted exosomes by small RNA sequencing and subsequent screening assays. Mechanistically, exosomal miR-181d-5p transferred from CAFs to RCC cells directly suppressed the expression of ring finger protein 43 (RNF43) and activated Wnt/β-catenin signaling pathway, thus promoted cancer stemness and tumor progression. Overexpression of RNF43 strongly suppressed stemness properties and the effects could be reverted by miR-181d-5p. Overall, our findings revealed a crucial mechanism by which CAFs secreted exosomal miRNAs to enhance cancer stemness and thus promote RCC progression, suggesting a new avenue based on CAF secreted miRNAs for more effective targeted therapies.
2022-11-09 | GSE213453 | GEO
Project description:Objective: To investigate the effects of stretch-induced periodontal ligament cell (PDLC) exosomes on osteoblast differentiation, and to explore their regulatory role in mechanical force-related periodontal tissue remodeling.Design: After applying 20% stretch loading to human periodontal ligament cells, exosomes were extracted from the supernatant and co-cultured with osteoblasts to detect their effects on osteogenic differentiation. Meanwhile, the exosomes were sequenced by high-throughput microRNA sequencing for bioinformatic analysis and validation to explore exosome signaling pathways through miRNAs.Results: Stretch-induced PDLC exosomes could be taken up by osteoblasts and promoted osteogenic differentiation of osteoblasts, as demonstrated by the increased expression levels of osteogenesis-related factors and enhanced ALP staining. In the miRNA profile of differentially expressed PDLC exosomes under stretch loading, miRNA-181d-5p was up-regulated significantly. The expression levels of osteogenesis-related factors and ALP staining were also increased in osteoblasts transfected with miR-181d-5p, and this effect might be related to the inhibitory role of exosomal miR-181d-5p on tumor necrosis factor (TNF).Conclusions: Stretch-induced PDLC exosomes exhibited a promoting effect on osteogenic differentiation, which might result from the inhibition of TNF via exosomal miR-181d-5p.
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Project description:Renal interstitial fibrosis(RIF) is an incurable pathological lesion in progressive chronic kidney diseases. Myofibroblasts proliferation and microvascular damage are two important events of RIF and pericyte is one of the major sources of myofibroblasts in kidney. However, the underlying mechanisms remain poorly characterized. Here we present that core fucosylation (CF), a posttranslational modification of proteins, is essential for pericyte activation via regulating of profibrotic and antifibrotic signaling pathway as a “hub-like” target. Exosomes deriving from MSCs specifically reside in obstructed kidney and deliver microRNA34c-5p to inhibit CF resulting in reducing pericyte activation and renal fibrosis. Furthermore, we clarify that the ligands and receptors (CD81-EGFR) complex assists the entrance of exosomal microRNA34c-5p into pericytes. Our results reveal a novel mechanism of pericyte activation base on CF and suggest a potential use of MSCs exosome as a new therapeutic strategy for renal interstitial fibrosis through inhibiting CF, the “hub-like” target of profibrotic signaling activation.
2020-11-04 | PXD022358 |
Project description:This experiment is designed to investigate the impact of exosomal miR-145-5p on the functional pathway and molecules on RPTEC cells. Data-independent acquisition (DIA) proteomics was conducted in the RPTEC cells transfected with miR-145-5p mimic or scramble control.
2023-03-28 | PXD041158 |
Project description:Adult renal stem/progenitor cells (ARPCs), first identified in the BowmanM-bM-^@M-^Ys capsule, were recently identified also in the tubular compartment and it was demonstrated that renal progenitors from both locations were positive for PAX-2, CD133 and CD24 and exhibited multipotent differentiation ability. Recent studies indicated that microRNAs (miRNAs), a class of noncoding small RNAs that participate in the regulation of gene expression, may play a key role in stem cell self-renewal and differentiation. Distinct sets of miRNAs are specifically expressed in pluripotent stem cells but not in adult tissues, suggesting a role for miRNAs in stem cell self-renewal. We compared miRNA expression profiles of renal progenitors with that of renal proximal tubular cells (RPTECs) and of mesenchymal stem cells (MSC) and found distinct sets of miRNAs that were specifically expressed both in tubular and glomerular ARPCs. In particular, the miR-1915 and miR-1225-5p regulated the expression of important markers of renal progenitors, such as CD133 and PAX-2, and important genes involved in the repair mechanisms of ARPCs, such as TLR2. We demonstrated that the expression of both the renal stem cell markers CD133 and PAX-2 depends, at least in part, on lower miR-1915 levels and showed that the increase of miR-1915 levels improved capacity of ARPCs to differentiate into adipocyte-like and epithelial-like cells. Finally, we found that the low levels of miR-1225-5p were responsible for high TLR2 expression in ARPCs. Therefore, together, the miR-1915 and the miR-1225-5p seems to regulate important trait of ARPCs: the stemness and the repair capacity. Sixteen samples consisting of 5 glomerular and tubular ARPCs each, 3 MSCs, and 3 RPTECS.
2013-05-30 | E-GEOD-42391 | biostudies-arrayexpress
Project description:Adult renal stem/progenitor cells (ARPCs), first identified in the Bowman’s capsule, were recently identified also in the tubular compartment and it was demonstrated that renal progenitors from both locations were positive for PAX-2, CD133 and CD24 and exhibited multipotent differentiation ability. Recent studies indicated that microRNAs (miRNAs), a class of noncoding small RNAs that participate in the regulation of gene expression, may play a key role in stem cell self-renewal and differentiation. Distinct sets of miRNAs are specifically expressed in pluripotent stem cells but not in adult tissues, suggesting a role for miRNAs in stem cell self-renewal. We compared miRNA expression profiles of renal progenitors with that of renal proximal tubular cells (RPTECs) and of mesenchymal stem cells (MSC) and found distinct sets of miRNAs that were specifically expressed both in tubular and glomerular ARPCs. In particular, the miR-1915 and miR-1225-5p regulated the expression of important markers of renal progenitors, such as CD133 and PAX-2, and important genes involved in the repair mechanisms of ARPCs, such as TLR2. We demonstrated that the expression of both the renal stem cell markers CD133 and PAX-2 depends, at least in part, on lower miR-1915 levels and showed that the increase of miR-1915 levels improved capacity of ARPCs to differentiate into adipocyte-like and epithelial-like cells. Finally, we found that the low levels of miR-1225-5p were responsible for high TLR2 expression in ARPCs. Therefore, together, the miR-1915 and the miR-1225-5p seems to regulate important trait of ARPCs: the stemness and the repair capacity.
2013-05-30 | GSE42391 | GEO
Project description:The aim of this study was to identify and evaluate exosomal miRNAs in serum as early diagnostic markers for gastric cancer (GC). Methods: Using next-generation sequencing (NGS) and bioinformatics, we identified candidate serum exosomal miRNA markers for early detection of GC in patients. The candidates were further validated by qRT-PCR in 50 newly recruited early-stage GC patients and matched healthy individuals. Results: NGS revealed that the average mappable reads in the RNA libraries were about 6.5 million per patient. A total of 66 up and 13 down-regulated exosomal miRNAs were found in the screened cohort after removal of log2 transformed read counts <5 and p >0.05. In the validation cohort, by comparing candidate exosomal miRNAs levels in early-stage GC patients and healthy individuals, higher levels of miR-92b-3p, let-7g-5p, miR-146b-5p and miR-9-5p were found to be significantly associated with GC. Diagnostic power of the combined panels of the exosomal miRNAs or the combination of exosomal miRNAs and CEA outperformed that of single exosomal miRNA marker for establishing a diagnosis of early-stage GC. In addition, serum levels of exosomal miR-92b-3p were significantly associated with low adhesion, let-7g-5p and miR-146b-5p were significantly correlated with nerve infiltration, and miR146b-5p was statistically correlated with tumor invasion depth in early-stage GC. Conclusions: Serum exosomal miR-92b-3p, -146b-5p, -9-5p, and let-7g-5p may serve as potential noninvasive biomarkers for early diagnosis of GC. Further validation of these candidate exosomal miRNAs in larger experimental cohorts are required in order to confirm the diagnostic values.
2020-02-21 | GSE130654 | GEO
Project description:Exosome-derived miRNAs are regarded as biomarkers for the diagnosis and prognosis of many human cancers. However, its function in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, differentially expressed miRNAs from urinal exosomes were identified using next-generation sequencing (NGS) and verified using urine samples of ccRCC patients and healthy donors. Then the exosomes were analyzed in early-stage ccRCC patients, healthy individuals and patients suffering with other urinary system cancers. Afterwards, the target gene of the miRNA was detected. Its biological function was investigated in vitro and in vivo. The results showed that miR-30c-5p could be stably amplified. Its expression pattern was significantly different only between ccRCC patients and healthy control individuals, but not compared with that of other urinary system cancers, which indicated its ccRCC specificity. Additionally, the overexpression of miR-30c-5p inhibited ccRCC progression in vitro and in vivo. Heat shock Protein 5 (HSPA5) was found to be a direct target gene of miR-30c-5p. HSPA5 depletion caused by miR-30c-5p inhibition reversed the promoting effect of ccRCC growth. In conclusion, urinary exosomal miR-30c-5p acts as a potential diagnostic biomarker of early-stage ccRCC, and might modulate the expression of HSPA5, which is correlated with the progression of ccRCC.
2019-04-03 | GSE129255 | GEO
Project description:Background: Renal cell carcinoma, which presents no significant clinical manifestations at early stages, is one of the few tumors with an increasing worldwide incidence. This malignancy cannot be directly detected by tumor markers in body fluid without information from imaging examinations. Approximately 30–40% of patients with kidney cancer exhibit distant metastasis at diagnosis, and their 5-year survival rate is much lower than that of patients with early-stage renal cell carcinoma. Thus, the early diagnosis of renal cell carcinoma is extremely important. The aim of this study was to investigate the utility of urinary exosomal long noncoding RNA (lncRNA) as a new potential diagnostic marker for renal cell carcinoma. Methods: Exosomes were isolated by ultracentrifugation from 50-ml urine samples from 10 patients with clear cell renal cell carcinoma and 10 matched healthy donors. Differentially expressed lncRNAs were analyzed by next-generation sequencing and further validated in kidney cancer cell lines, tissues and urinary exosomes. Then, we evaluated the sensitivity, specificity, clinical diagnostic value and stability of the selected lncRNAs. Results: The levels of lncRNAs NR_040448 and NR_033390 in urinary exosomes can likely indicate the presence of renal cell carcinoma. In addition, RNA protected by exosomes was stable enough to serve as a biomarker. Conclusion: Urinary exosomal lncRNA is a promising marker for the early diagnosis of renal cell carcinoma.
2019-01-23 | GSE125442 | GEO
Project description:Aims: Differential expression profiles of microRNAs (miRNAs) are associated with autoimmune diseases. This study sought to elucidate the plasma exosomal miRNA expression profiles of patients with rheumatoid arthritis (RA) and their potential clinical significance. Methods: In the screening phase, small RNA sequencing was performed to characterize dysregulated exosome-derived miRNAs in the plasma samples from six RA patients and six healthy controls. In the independent validation phase, the candidate plasma exosomal miRNAs were verified in 40 RA patients and 32 healthy controls using quantitative real-time PCR. The association of miRNA levels with clinical characteristics in RA patients was tested. The value of these miRNAs in diagnosing RA was assessed with the receiver operating characteristic curve. Results: Totally 177 and 129 miRNAs were upregulated and downregulated, respectively in RA patients versus healthy controls in the screening phase. There were 10 candidate plasma exosomal miRNAs selected for the next identification. Compared with the healthy controls, eight plasma exosomal miRNAs (let-7a-5p, let-7b-5p, let-7d-5p, let-7f-5p, let-7g-5p, let-7i-5p, miR-128-3p, and miR-25-3p) were significantly elevated in RA patients, but miR-144-3p and miR-15a-5p expression exhibited no significant changes. The let-7a-5p and miR-25-3p levels were associated with rheumatoid factor-positive phenotype in RA patients. For the eight miRNAs, the area under the receiver operating characteristic curve (AUC) ranged from 0.641 to 0.843, and their combination had a high diagnostic accuracy for RA (AUC = 0.916). Conclusions: Our study illustrates that novel exosomal miRNAs in the plasma may represent potential noninvasive biomarkers for RA.
2023-09-24 | GSE218599 | GEO