Antiproliferative and Pro-Apoptotic Effects of MiR-4286 Inhibition in Melanoma Cells

Abstract

IntroductionMicroRNAs are essential regulators of gene expression at the post-transcriptional level. Their expression is altered in cancer tissues, and evaluation of these alterations is considered a promising tool used to diagnose and identify prognostic markers.Materials and methodsThe microRNA expression profiles of formalin-fixed, paraffin-embedded melanoma and melanocytic nevi samples were estimated with a microarray and subsequently validated by real-time PCR. Melanoma cells were transfected with miR-4286 inhibitor to evaluate the influence of this microRNA on the viability, proliferation, apoptosis, migration, and invasion of melanoma cells.ResultsThe microarray revealed that the expression of 1,171 microRNAs was altered in melanoma samples compared to melanocytic nevi. Real-time PCR validation experiments found the microRNA expression levels to correspond to the melanoma/melanocytic nevi microarray results. The pathway analysis identified 52 modulated pathways in melanoma. Moreover, the application of miR-4286 inhibitor to BRO melanoma cells resulted in a 2.6-fold increase in the apoptosis rate and a 1.7-fold decrease in the cell proliferation/viability but did not affect the invasiveness and migration of these cells. Furthermore, the use of miR-4286 inhibitor altered the mRNA expression of several miR-4286 gene targets: folylpolyglutamate synthase, RNA polymerase I-specific transcription initiation factor, apelin, G-protein-coupled receptor 55, and high-mobility group A1 protein, which have been implicated in cell proliferation/apoptosis regulation. Lastly, the transiently transfected SK-MEL-1 cells with miR-4286 inhibitor decreased proliferation rate and modulated folylpolyglutamate synthase rates of these cells.ConclusionOur results demonstrate that miR-4286 mediates proliferation and apoptosis in melanoma cells, these findings may represent a novel mechanism underlying these processes.

miR‐155 overexpression is followed by downregulation of its target gene, NFE2L2, and altered pattern of VEGFA expression in the liver of melanoma B16‐bearing mice at the premetastatic stage

“…Our previous study found miR-155 to be the most notably upregulated and miR-205 the most notably downregulated microRNAs in melanoma, as compared with benign melanocytic tumours. 34 Those data are in accordance with several studies reporting the role of miR-155 as an oncogene and that of miR-205-5p as an oncosuppressor in various types of cancer. [35][36][37][38] Taken together, these findings prompted us to further investigate the target genes of miR-155 and miR-205.…”

MicroRNA‐4286 promotes cell proliferation, migration, and invasion via PTEN regulation of the PI3K/Akt pathway in non‐small cell lung cancer

“…In our previous analysis of miRNA arrays, we found that miR‐4286 level was significantly increased in NSCLC tissues . It has been reported that miR‐4286 is a promising marker for diagnosing and identifying prognostic markers, including those in esophageal adenocarcinoma and melanoma, and inhibition of miR‐4286 represses cell proliferation . But the role of miR‐4286 in NSCLC remains unknown.…”

“…6 It has been reported that miR-4286 is a promising marker for diagnosing and identifying prognostic markers, including those in esophageal adenocarcinoma 7,8 and melanoma, 9 and inhibition of miR-4286 represses cell proliferation. 10 But the role of miR-4286 in NSCLC remains unknown. In current study, we firstly report that miR-4286 is overexpressed in NSCLC tissues and cell lines and exerts important functions in cell proliferation, migration, and invasion of NSCLC.…”

MicroRNAs in cutaneous melanoma: Role as diagnostic and prognostic biomarkers

“…Komina et al () demonstrated that the application of a miR‐4286 inhibitor to melanoma cells resulted in a 2.6‐fold increase in the apoptosis rate and a 1.7‐fold decrease in cell proliferation, suggesting that this miRNA plays a role in protecting melanoma cells from apoptosis and promoting proliferation (Komina, Palkina, Aksenenko, Tsyrenzhapova, & Ruksha, ).…”

“…In fact, Hanna et al (2012) showed that decreased levels of miR-205 correlated with worse outcomes, independent of stage, age, gender, and Breslow depth (Hanna, Hahn, Agarwal, & Rimm, 2012). Komina et al (2016) demonstrated that the application of a miR-4286 inhibitor to melanoma cells resulted in a 2.6-fold increase in the apoptosis rate and a 1.7-fold decrease in cell proliferation, suggesting that this miRNA plays a role in protecting melanoma cells from apoptosis and promoting proliferation (Komina, Palkina, Aksenenko, Tsyrenzhapova, & Ruksha, 2016).…”