Similar Datasets
Project description:ObjectivesTo integrate mRNA and miRNA expression profiles of mucoepidermoid carcinomas (MECs) and normal salivary gland (NSGs) tissue samples and identify potential drivers.Material and methodsGene and miRNA expression arrays were performed in 35 MECs and six NSGs.ResultsWe found 46 differentially expressed (DE) miRNAs and 3,162 DE mRNAs. Supervised hierarchical clustering analysis of the DE transcripts revealed two clusters in both miRNA and mRNA profiles, which distinguished MEC from NSG samples. The integrative miRNA-mRNA analysis revealed a network comprising 696 negatively correlated interactions (44 miRNAs and 444 mRNAs) involving cell signaling, cell cycle, and cancer-related pathways. Increased expression levels of miR-205-5p and miR-224-5p and decreased expression levels of miR-139-3p, miR-145-3p, miR-148a-3p, miR-186-5p, miR-338-3p, miR-363-3p, and miR-4324 were significantly related to worse overall survival in MEC patients. Two overexpressed miRNAs in MEC (miR-22 and miR-205) were selected for inhibition by the CRISPR-Cas9 method. Cell viability, migration, and invasion assays were performed using an intermediate grade MEC cell line. Knockout of miR-205 reduced cell viability and enhanced ZEB2 expression, while miR-22 knockout reduced cell migration and invasion and enhanced ESR1 expression. Our results indicate a distinct transcriptomic profile of MEC compared to NSG, and the integrative analysis highlighted miRNA-mRNA interactions involving cancer-related pathways, including PTEN and PI3K/AKT.ConclusionThe in vitro functional studies revealed that miR-22 and miR-205 deficiencies reduced the viability, migration, and invasion of the MEC cells suggesting they are potential oncogenic drivers in MEC.
| S-EPMC8864291 | biostudies-literature
Project description:We used mRNA expression arrays and integrated analysis to study mucoepidermoid carcinomas (MEC) to identify potential drivers involved with its pathogenesis. Normal salivary glands were used as controls.
2022-03-03 | GSE169753 | GEO
Project description:We used miRNA expression arrays and integrated analysis to study mucoepidermoid carcinomas (MEC) to identify potential drivers involved with its pathogenesis. Normal salivary glands were used as controls.
2022-03-03 | GSE169692 | GEO
Project description:miR-22 and miR-205 drive tumor aggressiveness of mucoepidermoid carcinomas of salivary glands
| PRJNA717796 | ENA
Project description:miR-22 and miR-205 drive tumor aggressiveness of mucoepidermoid carcinomas of salivary glands [mRNA]
| PRJNA717800 | ENA
Project description:miR-22 and miR-205 drive tumor aggressiveness of mucoepidermoid carcinomas of salivary glands [miRNA]
| PRJNA717676 | ENA
Project description:A small sub-population of cells characterized by increased tumorigenic potential, ability to self-renew and to differentiate into cells that make up the tumor bulk, has been characterized in some (but not all) tumor types. These unique cells, namedcancer stem cells, are considered drivers of tumor progression in these tumors. The purpose of this work is to understand if cancer stem cells play a functional role in the tumorigenesis of salivary gland mucoepidermoid carcinomas. Here, we investigated the expression of putative cancer stem cell markers (ALDH, CD10, CD24, CD44) in primary human mucoepidermoid carcinomas by immunofluorescence, in vitro salisphere assays, and in vivo tumorigenicity assays in immunodeficient mice. Human mucoepidermoid carcinoma cells (UM-HMC-1, UM-HMC-3A, UM-HMC-3B) sorted for high levels of ALDH activity and CD44 expression (ALDHhighCD44high) consistently formed primary and secondary salispheres in vitro, and showed enhanced tumorigenic potential in vivo (defined as time to tumor palpability, tumor growth after palpability), when compared to ALDHlowCD44low cells. Cells sorted for CD10/CD24, and CD10/CD44 showed varying trends of salisphere formation, but consistently low in vivo tumorigenic potential. And finally, cells sorted for CD44/CD24 showed inconsistent results in salisphere formation and tumorigenic potential assays when different cell lines were evaluated. Collectively, these data demonstrate that salivary gland mucoepidermoid carcinomas contain a small population of cancer stem cells with enhanced tumorigenic potential and that are characterized by high ALDH activity and CD44 expression. These results suggest that patients with mucoepidermoid carcinoma might benefit from therapies that ablate these highly tumorigenic cells.
| S-EPMC4694941 | biostudies-literature
Project description:Acinic cell carcinomas (AcCC) of the breast have been reported to constitute the breast counterpart of salivary gland AcCCs, based on the similarities of their histological and immunohistochemical features. Breast AcCC is a vanishingly rare form of triple-negative breast cancer (TNBC). Recent studies have demonstrated that in TNBCs, the two driver genes most frequently mutated are TP53 (82%) and PIK3CA (10%). We sought to define whether breast AcCCs would harbour TP53 and PIK3CA somatic mutations, and if so, whether these would be present in salivary gland AcCCs.Sanger sequencing of the entire coding region of TP53 and of PIK3CA hotspot mutation sites of 10 breast and 20 salivary gland microdissected AcCCs revealed eight TP53 (80%) and one PIK3CA (10%) somatic mutations in breast AcCCs. No somatic mutations affecting these genes were found in the 20 salivary gland AcCCs analysed.Our findings demonstrate that breast AcCCs display TP53 and PIK3CA mutations at frequencies similar to those of common types of TNBCs, whereas these genes appear not to be altered in salivary gland AcCCs, suggesting that despite their similar histological appearances, AcCCs of the breast and salivary glands probably constitute unrelated diseases.
| S-EPMC5006393 | biostudies-literature
Project description:ObjectivesSalivary adenoid cystic carcinoma (SACC) is one of the most common salivary gland tumors in which patients encounter local recurrence and lung metastases. Understanding prognostic biomarkers in SACC is essential for future development in prognosis and treatment. This study aimed to assess the expression level of vascular endothelial growth factor (VEGF) and its potential regulatory microRNAs in SACC for prognostic determination. MATERIAL AND METHODS: The expression of VEGF in SACC samples was assessed using immunohistochemistry. Potential regulatory microRNAs were evaluated using quantitative reverse transcription-polymerase chain reaction. Associations between VEGF and microRNAs expression and clinicopathological parameters were investigated.ResultsVEGF expression levels positively correlated with histologic grade (p = .004) and treatment modality (p = .04). Decreased expression of miR-29a (p = .01) and increased expression of miR-93-5p and miR-205 (both p < .0001) were observed in SACC compared to normal salivary gland tissue. MiR-93-5p showed a positive association (p = .02) with VEGF overexpression.ConclusionsOur results showed the downregulation of miR-29 and overexpression of miR-93 and miR-205 in the SACC group, and the correlation between miR-93 and VEGF suggests these biomarkers as potential prognostic markers in the future.
| S-EPMC9932236 | biostudies-literature
Project description:Mucoepidermoid carcinoma (MEC) is the most common carcinoma of the salivary glands. Here, we have used two large patient cohorts with MECs comprising 551 tumors to study clinical, histological, and molecular predictors of survival. One cohort (n = 167), with known CRCT1/3-MAML2 fusion status, was derived from the Hamburg Reference Centre (HRC; graded with the AFIP and Brandwein systems) and the other (n = 384) was derived from the population-based Cancer Registry of North Rhine-Westphalia (LKR-NRW; graded with the AFIP system). The reliability of both the AFIP and Brandwein grading systems was excellent (n = 155). The weighted kappa for inter-rater agreement was 0.81 (95% CI 0.65-0.97) and 0.83 (95% CI 0.71-0.96) for the AFIP and Brandwein systems, respectively. The 5-year relative survival was 79.7% (95% CI 73.2-86.2%). Although the Brandwein system resulted in a higher rate of G3-MECs, survival in G3-tumors (AFIP or Brandwein grading) was markedly worse than in G1/G2-tumors. Survival in > T2 tumors was markedly worse than in those with lower T-stage. Also, fusion-negative MECs had a worse 5-year progression-free survival. The frequency of fusion-positive MECs in the HRC cohort was 78.4%, of which the majority (86.7%) was G1/G2-tumors. In conclusion, the AFIP and Brandwein systems are useful in estimating prognosis and to guide therapy for G3-MECs. However, their significance regarding young age (≤ 30 years) and location-dependent heterogeneity of in particular G2-tumors is more questionable. We conclude that CRTC1/3-MAML2 testing is a useful adjunct to histologic scoring of MECs and for pinpointing tumors with poor prognosis with higher precision, thus avoiding overtreatment.
| S-EPMC8572836 | biostudies-literature