The expression profiles of microRNAs in Kaposi’s sarcoma

Abstract

Kaposi's sarcoma (KS) is a multicentric angioproliferative tumor of mesenchymal origin. The molecular and biologic aspects of KS are not fully understood. MicroRNAs are non-protein-coding small RNAs in the size range 19-25 nucleotides (nt) that play important roles in biological processes, including cellular differentiation, proliferation, and death. We performed a miRNA microarray analysis by detecting six paired KS and matched adjacent healthy tissues using the 7th generation of miRCURY(TM) LNA Array (v.18.0) (Exiqon) containing 3100 capture probes. We selected 10 significant differentially expressed miRNAs, which were confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in 18 paired KS and matched adjacent healthy tissue specimens. We also investigated the associations between clinical features and miRNA expression. Among the 3100 human miRNA probes in the microarrays, we identified 170 differentially expressed miRNAs (69 upregulated and 101 downregulated miRNAs) in KS versus adjacent healthy tissues. Among the most significantly upregulated miRNAs were miR-126-3p, miR-199a-3p, miR-16-5p, and the 13 KSHV-related miRNAs. The most significantly downregulated miRNAs included miR-125b-1-3p and miR-1183. Eight upregulated miRNAs, miR-181b-5p, miR-199a-3p, miR-15a-5p, miR-126-3p, miR-1297, kshv-miR-k12-12-3p, kshv-miR-k12-1-5p, and miR-16-5p, and two downregulated miRNAs, miR-125b-1-3p and miR-1183, were confirmed by qRT-PCR in 18 paired KS samples. The qRT-PCR results for 10 miRNAs were consistent with our microarray results. The miR-125b-1-3p and miR-16-5p had statistically significant associations with HHV-8 and HIV infections in KS. The results of miRNA profiling showed that KS appears to have unique expression patterns when compared with paired adjacent healthy tissues, suggesting that deregulation of miRNAs plays an important role in the progression of KS. These differentially expressed miRNAs may provide novel diagnostic and prognostic tools.

A KSHV microRNA enhances viral latency and induces angiogenesis by targeting GRK2 to activate the CXCR2/AKT pathway

“…Due to the high expression levels of miR-K3 in KS lesions [41] and the crucial role that the miR-K3/GRK2/CXCR2/AKT axis might play in the KS pathogenesis [40], in this study, we have shown that, by targeting GRK2, miR-K3 not only facilitates KSHV latency, but also mediates KSHV-induced angiogenesis by activating the CXCR2/AKT pathway. These novel findings demonstrate that by targeting the GRK2/CXCR2/AKT pathway through encoding a miRNA, KSHV maintains its latency and induces a pro-angiogenic microenvironment to promote tumorigenesis.…”

“…This balance is controlled by RTA and regulated by latent gene products, such as LANA, cellular signaling pathways, and cellular and/or viral miRNAs [52]. As a KSHV-encoded miRNA, miR-K3 is highly expressed in KS tumors [41], and in KSHV-infected PEL cell lines [53, 54], indicating its potential role in viral lifecycle and its oncogenic potential. So far, the validated targets of miR-K3 included NFIB, MYB, C/EBPα, Ets-1 and GRK2 [19, 39, 40].…”

MicroRNA-224: as a potential target for miR-based therapy of cancer

“…The cross talk between these processes promotes a balance between the proliferation and apoptosis. Increasing studies have shown that miRNAs have important roles in cancer processes, including cell proliferation and apoptosis [24]. MiR-224 enhances the growth ability of CRC cells through accelerating the G1-S phase transition.…”

MicroRNA-126-3p suppresses cell proliferation by targeting PIK3R2 in Kaposi's sarcoma cells

“…One study showed that miR-143/145 is an upregulated miRNA biomarker and that miR-221/222, miR-155, and the let-7 family are downregulated in KS [11]. Wu et al [12] clearly identified 170 deregulated miRNAs: 69 were upregulated and 101 downregulated when compared between KS and matched adjacent healthy tissues. In particular, miR-126-3p and the 13 KSHV-related miRNAs were upregulated.…”