Action of HMGB1 on miR-221/222 cluster in neuroblastoma cell lines

Abstract

Abstract. microRNA (miR/miRNA) are small non-coding RNAs that control gene expression at the post-transcriptional level by targeting mRNAs. Aberrant expression of miRNAs is often observed in different types of cancer. Specific miRNAs function as tumor suppressors or oncogenes and interfere with various aspects of carcinogenesis, including differentiation, proliferation and invasion. Upregulation of miRNAs 221 and 222 has been shown to induce a malignant phenotype in numerous human cancers via inhibition of phosphatase and tensin homolog (PTEN) expression. Neuroblastoma is the most common extracranial solid malignancy in children, which is characterized by cellular heterogeneity that corresponds to different clinical outcomes. The different cellular phenotypes are associated with different gene mutations and miRs that control genetic and epigenetic factors. For this reason miRs are considered a potential therapeutic target in neuroblastoma. The aim of the present study was to investigate the mechanisms by which extracellular high mobility group box 1 (HMGB1) promotes cell growth in neuroblastoma. SK-N-BE(2) and SH-SY5Y neuroblastoma derived cell lines were transfected with the antisense oligonucleotides, anti-miR-221 and -222, followed by treatment with HMGB1 to investigate the expression of the oncosuppressor PTEN. In this study, it was demonstrated that HMGB1, which is released by damaged cells and tumor cells, upregulates miR-221/222 oncogenic clusters in the two human neuroblastoma derived cell lines. The results revealed that the oncogenic cluster miRs 221/222 were more highly expressed by the most undifferentiated cell line [SK-N-BE (2)] compared with the the less tumorigenic cell line (SH-SY5Y) and that exogenous HMGB1 increases this expression. In addition, HMGB1 modulates PTEN expression via miR-221/222, as demonstrated by transiently blocking miR-221/222 with anti-sense oligonucleotides. These results may lead to the development of novel therapeutic strategies for neuroblastoma.

N-(2′-Hydroxyphenyl)-2-propylpentanamide (OH-VPA), a histone deacetylase inhibitor, induces the release of nuclear HMGB1 and modifies ROS levels in HeLa cells

“…Several investigations of carcinogenesis-related mechanisms have identified important targets for therapy during cancer progression, including changes in redox state, metabolic reprogramming of tumor cells, and the inflammatory environment, among others [ 22 – 25 ]. The HMGB1 protein regulates diverse cell functions, and its overexpression could be a hallmark of cancer, others of which include unlimited replicative potential, angiogenesis, evasion of programmed cell death (apoptosis), self-sufficiency in growth signals, insensitivity to inhibitors of growth, inflammation, tissue invasion and metastasis [ 7 , 26 – 28 ]. HMGB1 is modified post-translationally by acetylation and is also sensitive to redox states [ 5 , 6 , 29 ].…”

MicroRNA-505 is downregulated in human osteosarcoma and regulates cell proliferation, migration and invasion

“…Indeed, Guo et al ( 40 ) proposed HMGB1 as a direct target of miR-22 in osteosarcoma, with miR-22 downregulating HMGB1-induced autophagy in osteosarcoma cells. HMGB1 was also reported to be involved in cell growth promotion in neuroblastoma by modulating PTEN expression, via miR-221/222 oncogenic clusters ( 41 ). Next, we confirmed that HMGB1 is a direct target of miR-505 in osteosarcoma cell lines, which was consistent with results revealed by Lu et al ( 27 ).…”

Graphene Oxide Nanoribbons Induce Autophagic Vacuoles in Neuroblastoma Cell Lines

“…Preliminary time and concentration course experiments with 0.2, 2, 4, 10 and 20 μg/mL of GO were performed in our laboratory in order to establish the conditions at which GO did not cause cell necrosis. Cell vitality was monitored before each experiment by Trypan blue (Sigma-Aldrich) [35] exclusion assay, in which dead cells are stained and those with intact membranes are not.…”