Dataset Information

Aberrant expression profiles and bioinformatic analysis of CAF-derived exosomal miRNAs from three moderately differentiated supraglottic LSCC patients.

ABSTRACT:

Background

Aberrant expression of exosomal miRNAs has emerged as a research hotspot. However, no studies have been conducted on the dysregulation of exosomal miRNAs derived from cancer-associated fibroblasts (CAFs) in supraglottic laryngeal squamous cell carcinoma (SLSCC).

Methods

Cancer-associated fibroblasts and paired normal fibroblasts (NFs) from SLSCC patients were cultured, and exosomes in the culture supernatants were collected and identified. Exosomal miRNA expression was compared in each pair of CAFs and NFs by next-generation sequencing, and expression of selected exosomal miRNAs was validated by reverse transcription-quantitative PCR. Four online bioinformatic algorithms predicted the potential target genes of aberrantly expressed miRNAs, while gene ontology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment and network analysis identified downstream target genes and their interactions.

Results

Three pairs of CAFs and NFs were successfully cultured and purified. CAF-derived exosomal miRNAs were mostly downregulated and included miR-656-3p, miR-337-5p, miR-29a-3p and miR-655-3p; however, some, including miR-184-3p, miR-92a-1-5p, miR-212-3p and miR-3135b, were upregulated. Bioinformatics analysis revealed involvement of these miRNAs in biological processes, cellular components and molecular functions. KEGG analysis revealed the top 30 pathways involvement in cancer initiation and progression and in cell cycle regulation. An interaction network showed miR-16-5p, miR-29a-3p, miR-34c-5p, miR-32-5p and miR-490-5p as the top five miRNAs and CCND1, CDKN1B, CDK6, PTEN and FOS as the top five target genes.

Conclusions

SLSCC patients showed aberrant expression of CAF-derived exosomal miRNAs. The top five miRNAs and their target genes may jointly constitute a carcinogenic tumour microenvironment and act as biomarkers for SLSCC intervention.

SUBMITTER: Wu C

PROVIDER: S-EPMC8761437 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Exosomes are small-diameter endosomal vesicles secreted in all biological fluids and play biological/pathological roles in the cell. These pathological roles are played by exosome's cargo molecules through inter-cellular communication. Exosomal cargo molecules contain proteins and miRNAs. miRNAs are small non-coding RNA fragments involved in the reduction of final protein output by destabilizing or suppressing the translation of target messenger RNA (mRNA). This deregulation of the protein due to miRNAs ultimately accelerates the process of disease pathogenesis. The role of exosomal miRNAs has been investigated in different diseases and the limited number of studies have been published concerning exosomal miRNAs and rheumatoid arthritis (RA). The current study is designed to investigate the role of exosomal miRNAs (miRNA-103a-3p, miRNA-10a-5p, miRNA-204-3p, miRNA-330-3p, and miRNA-19b) in the pathogenesis of RA. Furthermore, the role of selected exosomal miRNAs in RA pathogenesis was further explored by estimating oxidative stress and histone deacetylation in RA patients. In the current study, 306 RA patients and equal numbers of age/gender-matched controls were used. The level of expression of above-mentioned exosomal miRNAs was assessed by performing qRT PCR. Deacetylation and oxidative stress assays were performed to estimate the 8-hydroxydeoxyguanosine (8-OHdG level) and histone deacetylation levels using the Enzyme-linked immunosorbent assay (ELISA). Statistical analysis indicated a significantly downregulated expression of miRNA-103a-3p (p<0.0001), miR-10a-5p (p<0.0001), miR-204-3p (p<0.0001), miR-330-3p (p<0.0001) and miR-19b (p<0.0001) in RA patients compared to controls. Significantly increased levels of 8-OHdG (p<0.0001) and histone deacetylation (p<0.0001) were observed among RA patients compared to controls. Spearman correlation showed a negative correlation between the deregulated exosomal miRNAs and increased oxidative stress and histone deacetylation in RA patients. Receiver operating characteristics (ROC) curve analysis showed a good diagnostic specificity/sensitivity of the above-mentioned exosomal miRNAs among RA patients. These analyses indicated the potential role of deregulated exosomal miRNAs in the initiation of RA by targeting oxidative stress and histone deacetylation processes.