Research Article miR-367 promotes uveal melanoma cell proliferation and migration by regulating PTEN.

Abstract

ABSTRACT. We aimed to investigate the biological role of miR-367 in uveal melanoma cell growth and migration, and the underlying mechanism responsible. Quantitative real-time polymerase chain reaction was performed to evaluate miR-367 expression in uveal melanoma tissue samples and cell lines. A miR-367 mimic, miR-367 inhibitor, and negative control oligonucleotide were transfected into these cells to investigate the function of this microRNA. In addition, the role of PTEN in miR-367-mediated uveal melanoma cell growth and migration was evaluated. miR-367 was significantly upregulated in uveal melanoma cells and tissue samples (both P < 0.01). Its inhibition suppressed the proliferation, cell cycle transition, and migration of such cells, and increased levels had the opposite effect. PTEN was confirmed to be a target gene of miR-367. More importantly, co-transfection with a PTEN construct lacking the 3'-untranslated region mitigated miR-367 mimic-induced promotion of uveal melanoma cell proliferation and migration. In summary, miR-367 was found to be upregulated in this malignancy, and may promote uveal melanoma cell proliferation and migration, at least in part by regulating PTEN.

MicroRNAs and Uveal Melanoma: Understanding the Diverse Role of These Small Molecular Regulators

“…Other oncogenic miRNAs include miR-155 [85], miR-20a [86], and miR-216a-5p that targets the hexokinase 2 (HK 2 ) gene involved in cell metabolism [87]. Interestingly, two oncogenic miRNAs have been shown to target PTEN in UM, namely miR-454 [88] and miR-367 [89]. Both miRNAs were upregulated in UM cell lines and samples, and had significant effects on promoting cell proliferation, cell cycle, migration and invasion by directly targeting PTEN.…”

“…Both miRNAs were upregulated in UM cell lines and samples, and had significant effects on promoting cell proliferation, cell cycle, migration and invasion by directly targeting PTEN. Individually, miR-454 has been reported to be involved in hepatic stellate cell activation [90], while both miRNAs are involved in TGFβ signalling pathways via the SMAD family of genes [89,91]. These studies highlight that multiple miRNAs are able to target a single gene, and also that data from "single gene-single target" studies must be viewed in a wider context when trying to determine the overall miRNA landscape of UM.…”

Oncogenic signaling in uveal melanoma

“…PTEN immunoreactivity is either lost or weak in 59% of UM, and although PTEN mutations are not common, loss of heterozygosity of at least one PTEN marker was evident in 29 of 38 (76%) tumors, suggesting submicroscopic deletions within the PTEN gene (Abdel‐Rahman et al., ). PTEN expression is also downregulated in UM by overexpression of the microRNAs miR‐367 and miR‐454 (Ling, Lu, Zhang, Jiang, & Zhang, ; Sun et al., ). Importantly, loss of cytoplasmic PTEN expression is associated with shortened disease‐free survival in UM (Abdel‐Rahman et al., ).…”

Update on uveal melanoma: Translational research from biology to clinical practice (Review)

“…Recently, Serocki et al (148) confirmed the role of miR-17 family miRNAs in controlling HIF expression under conditions of hypoxia. Some miRNAs also reduce the expression of phosphatase and tensin homolog (PTEN), promoting PI3K/AKt/mTOR pathway activation (149,150). In addition, Liu et al (151) described the role of miR-216a-5p as an indicator of a better prognosis due to its inhibitory effect on hexokinase 2, an enzyme overexpressed in a wide array of tumours that is directly related to induction of the Warburg effect.…”