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Downstream Target Analysis for miR-365 among Oral Squamous Cell Carcinomas Reveals Differential Associations with
Brendon Yu1, Nathaniel Kruse1, Katherine M Howard2
1Department of Clinical Sciences, School of Dental Medicine, University of Nevada-Las Vegas, 1700 W. Charleston Boulevard, Las Vegas, NV 89106, USA.
Abstract:
Expression of microRNAs, such as miR-365, is known to be dysregulated in many tumors, including oral cancers, although little is known about their role or functions. The objective of this project is to evaluate the downstream targets of miR-365 to determine any potential pathways or effects. Downstream targets for miR-365 (miRdatabase target scores > 90) were used for qPCR screening of oral cancer cell lines (SCC4, SCC9, SCC15, SCC25, CAL27). Each oral cancer cell line expressed miR-365 downstream targets molybdenum cofactor synthesis-2 (MOCS2), erythropoietin receptor (EPOR), IQ motif containing-K (IQCK), carboxypeptidase A3 (CPA3), solute carrier family 24 member-3 (SLC24A3), and coiled-coil domain containing 47 (CCDC47)-although the expression levels varied somewhat. However, differential results were observed with ubiquitin protein ligase E3 component n-recognin-3 (UBR3), nudix hydrolase-12 (NUDT12), zinc finger CCHC-type containing-14 (ZCCHC14), and homeobox and leucine zipper encoding (HOMEZ). These data suggest that many of the miR-365 targets are expressed in the oral cancers screened, with the differential expression of UBR3, ZCCHC14, HOMEZ, and NUDT12, which may be correlated with chemoresistance among two specific oral cancer cell lines (SCC25, SCC9). These results suggest this differential expression may signal potential targets for patient treatment with tumors exhibiting miR-365 and chemotherapeutic resistance.
Insights
MicroRNA-365 (miR-365) targets are expressed in oral cancers. Differential expression of specific targets like UBR3, ZCCHC14, HOMEZ, and NUDT12 may correlate with chemoresistance, suggesting potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA-365 (miR-365) expression is dysregulated in oral cancers, but its functional roles and downstream targets remain largely uncharacterized.
- Understanding miR-365's impact is crucial for elucidating oral cancer pathogenesis and identifying novel therapeutic strategies.
Purpose of the Study:
- To identify and evaluate the downstream targets of miR-365 in oral cancer.
- To investigate the expression patterns of these targets across various oral cancer cell lines.
- To explore the potential correlation between miR-365 target expression and chemotherapeutic resistance.
Main Methods:
- Bioinformatic prediction of miR-365 downstream targets using miRdatabase (target scores > 90).
- Quantitative real-time PCR (qPCR) screening of selected targets in oral cancer cell lines (SCC4, SCC9, SCC15, SCC25, CAL27).
- Analysis of differential gene expression patterns among the cell lines.
Main Results:
- Several predicted miR-365 targets, including MOCS2, EPOR, IQCK, CPA3, SLC24A3, and CCDC47, were expressed in all screened oral cancer cell lines, albeit with varying levels.
- Differential expression was observed for ubiquitin protein ligase E3 component n-recognin-3 (UBR3), nudix hydrolase-12 (NUDT12), zinc finger CCHC-type containing-14 (ZCCHC14), and homeobox and leucine zipper encoding (HOMEZ).
- The differential expression of UBR3, ZCCHC14, HOMEZ, and NUDT12 in SCC25 and SCC9 cell lines may be linked to chemoresistance.
Conclusions:
- The study confirms the expression of numerous miR-365 targets in oral cancers.
- Differential expression of UBR3, ZCCHC14, HOMEZ, and NUDT12 suggests a potential role in chemoresistance in specific oral cancer subtypes.
- These differentially expressed genes represent potential therapeutic targets for patients with miR-365-related oral cancers exhibiting chemotherapeutic resistance.
