<p>kshv-mir-k12-1-5p promotes cell growth and metastasis by targeting SOCS6 in Kaposi’s sarcoma cells</p>

Abstract

Background: Kaposi’s sarcoma (KS) is a highly disseminated angiogenic tumour of endothelial cells. Many deregulated miRNAs, including kshv-mir-k12-1-5p, have been identified in KS. kshv-mir-k12-1-5p plays important roles in KS. However, the underlying mechanism is not fully understood. The aim of this study was to investigate the exact functions of kshv-mir-k12-1-5p in KS cells. Materials and methods: The biological functions of kshv-mir-k12-1-5p were studied using CCK-8, apoptosis, migration and invasion assays. Bioinformatics software was used to identify the target gene (SOCS6) of kshv-mir-k12-1-5p. A dual luciferase assay, Western blot (WB) and quantitative real-time polymerase chain reaction (q-PCR) were performed to further verify the target gene. The underlying molecular mechanisms of kshv-mir-k12-1-5p in KS cells were also explored. Results: kshv-mir-k12-1-5p can promote the proliferation, migration and invasion of KS cells and inhibit cell apoptosis. Suppressor of cytokine signalling 6 (SOCS6) was identified as a direct target of kshv-mir-k12-1-5p, and kshv-mir-k12-1-5p can downregulate SOCS6 expression. In addition, knockdown of SOCS6 rescued the effects of kshv-mir-k12-1-5p inhibitor. Hence, a direct relationship between kshv-mir-k12-1-5p and SOCS6 was confirmed. Conclusions: kshv-mir-k12-1-5p promotes the malignant phenotype of KS cells by targeting SOCS6, suggesting that kshv-mir-k12-1-5p could be a potential therapeutic target for KS.

Viral miRNAs as Active Players and Participants in Tumorigenesis

“…For example, kshv-miR-K12-1, -3, and -4-3p target and inactivate the inducer of apoptosis, Casp3, blocking apoptosis [64], while kshv-K12-1 functions as an oncogene by activating NF-κB/IL-6/STAT3 signaling [65]. Kshv-mir-K12-3 has been demonstrated to be a promoter of cell migration and invasion by targeting GRK2/CXCR2/AKT signaling [66], and kshv-miR-k12-1-5p has been shown to be a promoter of the proliferation, migration, and invasion of KS cells by suppressing cytokine signaling 6 (SOCS6) [67]. It has also been demonstrated that kshv-miR-K1-5p and kshv-miR-K4-5p directly target CASTOR1, inhibiting its expression and activating the mTORC1 pathway with the final result of promoting tumorigenesis [68].…”

Down-regulation of SOCS6: An Unfavorable Prognostic Factor for Gastrointestinal Stromal Tumor Proven by Survival Analysis

“…And the epigenetic modi cation of the promoter region such as methylation has been proven to lead to down-regulation or loss of SOCS6 expression [19]. A more recent study has demonstrated that miR-k12-1-5p could lead to decreased expression of SOCS6 in Kaposi's sarcoma [20]. In glioblastoma, up-regulation of miR-494 could result in reduced expression of SOCS6 [21].…”

Down-regulation of SOCS6: an unfavorable prognostic factor for gastrointestinal stromal tumor proven by survival analysis

“…And the epigenetic modification of the promoter region such as methylation has been proven to lead to down-regulation or loss of SOCS6 expression [ 18 ]. A more recent study reported that miR-k12-1-5p could lead to decreased expression of SOCS6 in Kaposi’s sarcoma [ 19 ]. In glioblastoma, up-regulation of miR-494 could result in reduced expression of SOCS6 [ 20 ].…”