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MiRNAs that target amyloid precursor protein processing machinery in extracellular vesicles and particles derived
Fernando Galvão1, Michele Patricia Rode2, Paloma Santos de Campos3
1Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Background:
Considering that microRNAs (miRNAs), extracellular vesicles and particles (EVPs) and the amyloid precursor protein (APP) processing have been shown to be altered in oral squamous cells carcinoma (OSCC), it is possible that miRNAs that target APP processing pathways in EVPs are impacted in tumor cells. Our aim was to evaluate miRNAs that target APP itself or disintegrin and metalloproteinase domain 10 (ADAM10), which generate a trophic compound, sAPPα, in EVPs derived from OSCC cell lines, an aggressive and non-invasive, compared to normal keratinocytes.
Methods:
We used two OSCC cell lines, an aggressive human oral squamous cell carcinoma cell line (SCC09) and a less aggressive cell line (CAL27) compared with a keratinocyte lineage (HaCaT). Cells were maintained in cell media, from which we isolated EVPs. EVPs were evaluated regarding their size and concentration using Nanotracking Analysis. We measured the levels of miRNAs which had as potential downstream target APP or ADAM10, specifically miR-20a-5p, miR-103a-3p, miR-424-5p, miR-92b-3p, miR-31-5p, and miR-93-5.
Results:
There were no differences on size distributions and concentration of isolated EVPs. OSCC cell lines-derived EVPs miR-20a-5p, miR-92b-3p, and miR-93-5p were upregulated in comparison to HaCaT-derived EVPs; while miR-31-5p was reduced in EVPs obtained from CAL27 cells.
Conclusion:
Our results indicate changes in miRNAs that target APP machinery processing in EVPs derived from OSCC cell lines of different aggressiveness, which may be involved with abnormal miRNA expression in OSCC tissue and/or releasing tumor suppressor miRNA.
Insights
MicroRNAs (miRNAs) targeting amyloid precursor protein (APP) processing in extracellular vesicles and particles (EVPs) are altered in oral squamous cell carcinoma (OSCC). These findings suggest potential roles in OSCC development and as tumor suppressors.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Oral squamous cell carcinoma (OSCC) is associated with alterations in microRNAs (miRNAs), extracellular vesicles and particles (EVPs), and amyloid precursor protein (APP) processing.
- Investigating miRNAs within EVPs that target APP processing pathways is crucial for understanding OSCC pathogenesis.
Purpose of the Study:
- To evaluate miRNAs targeting APP or ADAM10 in EVPs derived from OSCC cell lines.
- To compare miRNA profiles in aggressive and non-aggressive OSCC cell lines against normal keratinocytes.
Main Methods:
- Utilized two OSCC cell lines (SCC09, CAL27) and a keratinocyte lineage (HaCaT).
- Isolated EVPs and analyzed their size and concentration via Nanotracking Analysis.
- Quantified levels of specific miRNAs (miR-20a-5p, miR-103a-3p, miR-424-5p, miR-92b-3p, miR-31-5p, miR-93-5p) targeting APP or ADAM10.
Main Results:
- No significant differences in EVP size distribution or concentration were observed between cell lines.
- EVPs from OSCC cell lines showed upregulated miR-20a-5p, miR-92b-3p, and miR-93-5p compared to HaCaT.
- miR-31-5p was found to be reduced in EVPs from CAL27 cells.
Conclusions:
- Changes in miRNAs targeting the APP processing machinery within EVPs from OSCC cell lines of varying aggressiveness were identified.
- These alterations may contribute to abnormal miRNA expression in OSCC tissues.
- The study suggests a potential role for these miRNAs as tumor suppressors in OSCC.
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