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Oncomirs Expression Profiling in Uterine Leiomyosarcoma Cells
Bruna Cristine de Almeida1, Natalia Garcia2, Giovana Maffazioli3
1Laboratório de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Departamento de Obstetricia e Ginecologia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, HCFMUSP, SP, BR Av. Dr Arnaldo 455, sala 4121, 05403-010 Cerqueira Cesar, São Paulo, Brazil. bruc_10@hotmail.com.
Abstract:
MicroRNAs (miRNAs) are small non-coding RNAs that act as regulators of gene expression at the post-transcriptional level. They play a key role in several biological processes. Their abnormal expression may lead to malignant cell transformation. This study aimed to evaluate the expression profile of 84 miRNAs involved in tumorigenesis in immortalized cells of myometrium (MM), uterine leiomyoma (ULM), and uterine leiomyosarcoma (ULMS). Specific cell lines were cultured and qRT-PCR was performed. Thirteen miRNAs presented different expression profiles in ULM and the same thirteen in ULMS compared to MM. Eight miRNAs were overexpressed, and five were underexpressed in ULM. In ULMS cells, five miRNAs exhibited an overexpression and eight were down-regulated. Six miRNAs (miR-1-3p, miR-130b-3p, miR-140-5p, miR-202-3p, miR-205-5p, and miR-7-5p) presented a similar expression pattern in cell lines compared to patient samples. Of these, only three miRNAs showed significant expression in ULM (miR-1-3p, miR-140-5p, and miR-7-5p) and ULMS (miR-1-3p, miR-202-3p, and miR-7-5p). Our preliminary approach identified 24 oncomirs with an altered expression profile in ULM and ULMS cells. We identified four differentially expressed miRNAs with the same profile when compared with patients' samples, which strongly interacted with relevant genes, including apoptosis regulator (BCL2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA), insulin like growth factor 1 receptor (IGF1R),serine/threonine kinase (RAF1), receptor tyrosine kinase (MET), and bHLH transcription factor (MYCN). This led to alterations in their mRNA-target.
Insights
MicroRNAs (miRNAs) regulate gene expression and are implicated in cancer. This study identified specific miRNAs with altered expression in uterine leiomyoma and leiomyosarcoma cells, potentially impacting key cancer-related genes.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs regulating gene expression post-transcriptionally.
- Aberrant miRNA expression is linked to malignant cell transformation and tumorigenesis.
- Uterine leiomyoma (ULM) and uterine leiomyosarcoma (ULMS) are common gynecological tumors with complex molecular underpinnings.
Purpose of the Study:
- To investigate the expression profiles of 84 miRNAs associated with tumorigenesis.
- To compare miRNA expression in immortalized myometrium (MM), ULM, and ULMS cell lines.
- To identify specific miRNAs with altered expression patterns in ULM and ULMS relevant to patient samples.
Main Methods:
- Culturing of MM, ULM, and ULMS cell lines.
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) for miRNA expression analysis.
- Comparison of miRNA expression data between cell lines and patient samples.
Main Results:
- Thirteen miRNAs showed differential expression in ULM and ULMS compared to MM cell lines.
- Eight miRNAs were overexpressed and five underexpressed in ULM; five overexpressed and eight down-regulated in ULMS.
- Six miRNAs (miR-1-3p, miR-130b-3p, miR-140-5p, miR-202-3p, miR-205-5p, miR-7-5p) exhibited similar patterns in cell lines and patient samples.
- Four differentially expressed miRNAs (miR-1-3p, miR-140-5p, miR-7-5p in ULM; miR-1-3p, miR-202-3p, miR-7-5p in ULMS) showed significant expression changes and interacted with cancer-related genes (BCL2, EGFR, VEGFA, IGF1R, RAF1, MET, MYCN).
Conclusions:
- Identified 24 oncomiRs with altered expression in ULM and ULMS cells.
- Four specific miRNAs demonstrated consistent dysregulation in both cell lines and patient samples.
- These miRNAs interact with critical genes involved in apoptosis, growth factor signaling, and angiogenesis, suggesting their role in uterine tumor development.
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