Oncomirs Expression Profiling in Uterine Leiomyosarcoma Cells

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.

Could miRNA Signatures be Useful for Predicting Uterine Sarcoma and Carcinosarcoma Prognosis and Treatment?

“…miR-146b exerts potential effects on EGFR by the NFKBI signaling pathway. EGFR was described as immunolocalized of its proteins in the cytoplasm of smooth-muscle cells in the leiomyoma and matched myometrium [ 8 , 36 ]. Strong interactions might be seen between miR-146b and CDKN1A , which is an important regulator of cell cycle progression at G1 and can act as a positive regulator of senescence-like terminal proliferation arrest, but its function seems neither sufficient nor absolutely required for a treatment response to doxorubicin in tumor cells, especially soft tissue sarcoma [ 35 ].…”

“…IGF1R was detected in the uterus and its expression levels were significantly higher in uterine fibroids. There is a hypothesis that the fibroids’ transformation is the main cause of LMS [ 3 , 8 ]. The main function of the IGF1R as a survival factor is to inhibit apoptosis, being able to increase the tumorigenic potential under some conditions, which protects them from programmed cell death when over-expressed [ 40 ].…”

“…Epigenetic studies have demonstrated that microRNAs (miRNAs) are involved in multiple biological functions, including regulation of gene expression at the posttranscriptional level, cell proliferation, apoptosis, metabolism, angiogenesis, and others [ 8 , 9 , 10 ]. Thereby, miRNA differential expression caused by chromosomal alterations might lead to cancer development and/or its progression [ 10 ].…”

The Role of miRNA and Related Pathways in Pathophysiology of Uterine Fibroids—From Bench to Bedside

“…However, only 3 miRNAs (miR-1-3p, miR-7-5p, miR-140-5p) showed a significant change in expression in UFs. In LMS a significant overexpression was found for miR-1-3p, miR-7-5p and miR-202-3p [130].…”

“…At the same time, serum LDH had the AUC of only 0.64 and 95% confidence interval of 0.34-0.94 [129]. Earlier in 2017, de Almeida et al [130] also presented data on miRNAs expression in UFs in differential diagnosis. They did not construct the model as mentioned above, but their data were also of importance.…”