AI Article Synopsis
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by targeting mRNAs and play a significant role in cancer development, acting as either tumor suppressors or oncogenes.
- * Aberrant expression of miR-221 and -222 is linked to promoting malignancy in various cancers by inhibiting the expression of the oncosuppressor PTEN.
- * The study focused on how high mobility group box 1 (HMGB1) enhances cell growth in neuroblastoma by upregulating miR-221/222, affecting PTEN expression, which could provide new therapeutic options for treating this childhood cancer.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998517 | PMC |
| http://dx.doi.org/10.3892/ol.2016.4876 | DOI Listing |
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