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.
Highlights
MicroRNAs are endogenous 17–27 nucleotide-long non-coding RNAs acting as regulators of gene expression at the posttranscriptional level by inhibiting protein synthesis
Some miRNAs were previously identified as having altered expression in uterine leiomyoma (ULM) and in Uterine leiomyosarcoma (ULMS) [12]
The present study aims to evaluate the expression profile of 84 oncomir sequences in immortalized cells of myometrium (MM), ULM, and ULMS
Summary
MicroRNAs (miRNAs) are endogenous 17–27 nucleotide-long non-coding RNAs acting as regulators of gene expression at the posttranscriptional level by inhibiting protein synthesis. They play a key role in several biological processes [1], and, when abnormally expressed, may lead to cellular transformation and tumorigenesis. Uterine leiomyosarcoma (ULMS) is a smooth muscle [5] rare malignant tumor, representing about 1–2% of all uterine neoplasias [6,7] It is associated with a worse prognosis even when diagnosed early. The present study aims to evaluate the expression profile of 84 oncomir sequences in immortalized cells of myometrium (MM), ULM, and ULMS
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