Abstract

Kaposi's sarcoma is a highly vascular tumor of lymphatic endothelial origin. Many deregulated miRNAs, including miR-126-3p, have been identified in Kaposi's sarcoma tissues. miR-126-3p is the most highly endothelial-specific miRNA that regulates vascular integrity and angiogenesis. In this study, we aimed to determine the effect of miR-126-3p on Kaposi's sarcoma cells through transfection of a miRNA mimic and inhibitor. Moreover, we searched the target gene (PIK3R2) of miR-126-3p using bioinformatics software and further verified PIK3R2 using luciferase reporter assays, Real-time quantitative PCR (qRT-PCR) and western blot. The results demonstrated that miR-126-3p inhibited cell proliferation, arrested cell cycle progression, induced cell apoptosis, and inhibited cell invasion of SLK cells. The bioinformatics analysis and luciferase reporter assay revealed that PIK3R2 mRNA is a direct target of miR-126-3p. Moreover, the level of expression of the PIK3R2 gene was downregulated in SLK cells transfected with miR-126-3p siRNAs. Therefore, our data demonstrated that miR-126-3p is a tumor suppressor miRNA that acts by targeting PIK3R2 in Kaposi's sarcoma cells. These findings contribute to our understanding of the molecular mechanisms underlying Kaposi's sarcoma.

Highlights

  • Kaposi’s sarcoma (KS) is a multicentric tumor of mesenchymal origin which was first described by Moritz Kaposi in 1872 [1, 2]

  • We demonstrated the functional role of miR-126-3p in the proliferation of SLK cells after transfection with miR-126-3p mimics, inhibitor, negative control and inhibitor negative control

  • Deregulated expression of some miRNAs has been reported [11,12,13]; miRNAs are endogenous non-coding RNA molecules, 18–25 nucleotides in length, that negatively regulate downstream target genes. They play important functions in development, cell differentiation, and regulation of the cell cycle and apoptosis [21]. miRNAs can act as oncogenes and tumor suppressors associated with deregulated gene expression in cancer caused by gene amplification, deletion, mutation, and epigenetic silencing. miRNAs can guide the diagnosis, prognosis, and treatment of cancer [22, 23]. miR-126-3p inhibits cell migration, and is associated with reorganization of the cytoskeleton, vascular integrity, endothelial phenotype and cell survival in vitro and in vivo [15]

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Summary

Introduction

Kaposi’s sarcoma (KS) is a multicentric tumor of mesenchymal origin which was first described by Moritz Kaposi in 1872 [1, 2]. Another study showed that there were 185 differentially expressed miRNAs, of which 76 were upregulated and 109 were downregulated, in 17 formalin-fixed paraffin-embedded KS samples and three Kaposi’s sarcoma associated herpesvirus (KSHV) -negative normal Formalin fixed paraffin embedding (FFPE) samples [13]. These reports reveal that deregulated miRNAs are involved in the occurrence and development of KS

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