Small Extracellular Vesicles and Their Involvement in Cancer Resistance: An Up-to-Date Review

Słomka, Artur; Kornek, Miroslaw; Cho, William C.

doi:10.3390/cells11182913

Cited by 22 publications

(18 citation statements)

References 175 publications

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“…EVs are nanosized particles constantly secreted by all cells and their features reflect the state of the cell of origin, so that they can mirror tissue health and disease [ 22 , 23 , 24 ]. From a clinical perspective, EVs can be used as appropriate biomarkers to evaluate disease evolution.…”

Section: Discussionmentioning

confidence: 99%

“…It could be speculated that uEV cargo during DN may be involved in the amplification of diabetic-induced alterations via EV release or, alternatively, simply represent the modulation of the miRNA packaging in EVs from damaged renal cells. Understanding these intracellular mechanisms and precisely following the axis of miRNA-messenger RNA in kidney cells [ 23 , 24 , 25 , 36 ] is crucial for the future use of EVs in the clinical evaluation of DN. Further experiments are needed to clarify this aspect.…”

Section: Discussionmentioning

confidence: 99%

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Upregulation of miR145 and miR126 in EVs from Renal Cells Undergoing EMT and Urine of Diabetic Nephropathy Patients

Dimuccio

Bellucci²,

Genta³

et al. 2022

IJMS

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Diabetic nephropathy (DN) is a severe kidney-related complication of type 1 and type 2 diabetes and the most frequent cause of end-stage kidney disease. Extracellular vesicles (EVs) present in the urine mainly derive from the cells of the nephron, thus representing an interesting tool mirroring the kidney’s physiological state. In search of the biomarkers of disease progression, we here assessed a panel of urinary EV miRNAs previously related to DN in type 2 diabetic patients stratified based on proteinuria levels. We found that during DN progression, miR145 and miR126 specifically increased in urinary EVs from diabetic patients together with albuminuria. In vitro, miRNA modulation was assessed in a model of TGF-β1-induced glomerular damage within a three-dimensional perfusion system, as well as in a model of tubular damage induced by albumin and glucose overload. Both renal tubular cells and podocytes undergoing epithelial to mesenchymal transition released EVs containing increased miR145 and miR126 levels. At the same time, miR126 levels were reduced in EVs released by glomerular endothelial cells. This work highlights a modulation of miR126 and miR145 during the progression of kidney damage in diabetes as biomarkers of epithelial to mesenchymal transition.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Upregulation of miR145 and miR126 in EVs from Renal Cells Undergoing EMT and Urine of Diabetic Nephropathy Patients

Dimuccio

Bellucci²,

Genta³

et al. 2022

IJMS

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“…However, the exosomal lncRNA-HNF1A-AS1 has not been widely studied in the literature. Luo et al reported that exosomal lncRNA-HNF1A-AS1 secreted by the cisplatin-resistant cells could inhibit apoptosis of cervical tumors [ 42 , 43 ]. Moreover, the inhibition of exosomal lncRNA-HNF1A-AS1 could inhibit tumor formation in nude mice [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Expression Analysis of Five Different Long Non-Coding Ribonucleic Acids in Nonsmall-Cell Lung Carcinoma Tumor and Tumor-Derived Exosomes

et al. 2022

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Long non-coding ribonucleic acids (LncRNAs) are recently known for their role in regulating gene expression and the development of cancer. Controversial results indicate a correlation between the tissue expression of LncRNA and LncRNA content of extracellular vesicles. The present study aimed to evaluate the expression of different LncRNAs in non-small cell lung cancer (NSCLC) patients in tumor tissue, adjacent non-cancerous tissue (ANCT), and exosome-mediated lncRNA. Tumor and ANCT, as well as serum samples of 168 patient with NSCLC, were collected. The GHSROS, HNF1A-AS1, HOTAIR, HMlincRNA717, and LINCRNA-p21 relative expressions in tumor tissue, ANCT, and serum exosomes were evaluated in NSCLC patients. Among 168 NSCLC samples, the expressions of GHSROS (REx = 3.64, p = 0.028), HNF1A-AS1 (REx = 2.97, p = 0.041), and HOTAIR (REx = 2.9, p = 0.0389) were upregulated, and the expressions of HMlincRNA717 (REx = −4.56, p = 0.0012) and LINCRNA-p21 (REx = −5.14, p = 0.00334) were downregulated in tumor tissue in contrast to ANCT. Moreover, similar statistical differences were seen in the exosome-derived RNA of tumor tissues in contrast to ANCT samples. A panel of the five lncRNAs demonstrated that the area under the curve (AUC) for exosome and tumor was 0.937 (standard error: 0.012, p value < 0.0001). LncRNAs GHSROS, HNF1A-AS1, and HOTAIR showed high expression in tumor tissue and exosome content in NSCLC, and a panel that consisted of all five lncRNAs improved diagnosis of NSCLC.

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“…Unless here we focused on an axis involving (non-coding and coding) RNA molecules, data obtained on the expression of VEGFA mRNA suggest that IGFBP2 may be upstream regulated by circSMARCA5 also at the protein level: indeed, IGFBP2 was described as an enhancer for the transcription of VEGFA in neuroblastoma cells [ 93 ] and IGFBP2 and VEGFA were shown to be positively correlated at the protein level in GBM tissues [ 94 ]. MiR-126-3p can be also carried in biological fluids through EVs [ 95 , 96 ]: it would be interesting to investigate if and how the delivery of this molecule to cells at different sites from the bulk tumor play a role in the cancer progression and resistance to the current therapies. MiR-515-5p and its target NRAS are also known to be involved in GBM progression by regulating cell migration, growth [ 53 , 54 , 55 , 56 , 97 ], and angiogenesis [ 98 , 99 ].…”

Section: Discussionmentioning

confidence: 99%

circSMARCA5 Is an Upstream Regulator of the Expression of miR-126-3p, miR-515-5p, and Their mRNA Targets, Insulin-like Growth Factor Binding Protein 2 (IGFBP2) and NRAS Proto-Oncogene, GTPase (NRAS) in Glioblastoma

Merulla

Stella

Barbagallo

et al. 2022

IJMS

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The involvement of non-coding RNAs (ncRNAs) in glioblastoma multiforme (GBM) pathogenesis and progression has been ascertained but their cross-talk within GBM cells remains elusive. We previously demonstrated the role of circSMARCA5 as a tumor suppressor (TS) in GBM. In this paper, we explore the involvement of circSMARCA5 in the control of microRNA (miRNA) expression in GBM. By using TaqMan® low-density arrays, the expression of 748 miRNAs was assayed in U87MG overexpressing circSMARCA5. Differentially expressed (DE) miRNAs were validated through single TaqMan® assays in: (i) U87MG overexpressing circSMARCA5; (ii) four additional GBM cell lines (A172; CAS-1; SNB-19; U251MG); (iii) thirty-eight GBM biopsies; (iv) twenty biopsies of unaffected brain parenchyma (UC). Validated targets of DE miRNAs were selected from the databases TarBase and miRTarbase, and the literature; their expression was inferred from the GBM TCGA dataset. Expression was assayed in U87MG overexpressing circSMARCA5, GBM cell lines, and biopsies through real-time PCR. TS miRNAs 126-3p and 515-5p were upregulated following circSMARCA5 overexpression in U87MG and their expression was positively correlated with that of circSMARCA5 (r-values = 0.49 and 0.50, p-values = 9 × 10−5 and 7 × 10−5, respectively) in GBM biopsies. Among targets, IGFBP2 (target of miR-126-3p) and NRAS (target of miR-515-5p) mRNAs were positively correlated (r-value = 0.46, p-value = 0.00027), while their expression was negatively correlated with that of circSMARCA5 (r-values = −0.58 and −0.30, p-values = 0 and 0.019, respectively), miR-126-3p (r-value = −0.36, p-value = 0.0066), and miR-515-5p (r-value = −0.34, p-value = 0.010), respectively. Our data identified a new GBM subnetwork controlled by circSMARCA5, which regulates downstream miRNAs 126-3p and 515-5p, and their mRNA targets IGFBP2 and NRAS.

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Small Extracellular Vesicles and Their Involvement in Cancer Resistance: An Up-to-Date Review

Cited by 22 publications

References 175 publications

Upregulation of miR145 and miR126 in EVs from Renal Cells Undergoing EMT and Urine of Diabetic Nephropathy Patients

Upregulation of miR145 and miR126 in EVs from Renal Cells Undergoing EMT and Urine of Diabetic Nephropathy Patients

Expression Analysis of Five Different Long Non-Coding Ribonucleic Acids in Nonsmall-Cell Lung Carcinoma Tumor and Tumor-Derived Exosomes

circSMARCA5 Is an Upstream Regulator of the Expression of miR-126-3p, miR-515-5p, and Their mRNA Targets, Insulin-like Growth Factor Binding Protein 2 (IGFBP2) and NRAS Proto-Oncogene, GTPase (NRAS) in Glioblastoma

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