Zhao Dongju, Tian Yunjiao, Li Peiling, Wang Limin, Xiao Aiju, Zhang Mingqiu, Shi Taixin
Department of Pediatrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
Department of Interventional Radiography, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
Mol Med Rep. 2015 Oct;12(4):5554-60. doi: 10.3892/mmr.2015.4013. Epub 2015 Jul 1.
Neuroblastoma (NB) is the most common solid extracranial tumor in children. However, the molecular mechanism of NB remains to be elucidated. In the present study, reverse transcription quantitative polymerase chain reaction data demonstrated that the expression of Sam68 was significantly upregulated in NB tissues compared with their matched adjacent normal tissues. Furthermore, it was revealed that reduced expression of miR‑203 and increased expression of Sam68 co‑existed in NB tissues. Knockdown of Sam68 reduced the proliferation, migration and invasion of human SK‑N‑SH and SH‑SY5Y NB cells. Similarly, overexpression of miR‑203 also inhibited the proliferation, migration and invasion of these two cell lines. It was further demonstrated that the protein expression level of Sam68 was negatively mediated by miR‑203 in the SK‑N‑SH and SH‑SY5Y NB cells. Additionally, data from a dual luciferase reporter assay confirmed that miR‑203 directly targeted Sam68 by binding to its 3'‑untranslated region. In conclusion, the present study suggested for the first time, to the best of our knowledge, that the aberrant downregulation of miR‑203 may contribute to the aberrant upregulation of Sam68 in NB and that miR‑203 has an inhibitory role in malignant progression of NB by targeting Sam68. The present study provided evidence to support miR-203/Sam68 as a novel diagnostic or therapeutic targets for NB.
神经母细胞瘤（NB）是儿童最常见的实体颅外肿瘤。然而，NB的分子机制仍有待阐明。在本研究中，逆转录定量聚合酶链反应数据表明，与匹配的相邻正常组织相比，Sam68在NB组织中的表达显著上调。此外，研究发现NB组织中miR-203表达降低与Sam68表达增加并存。敲低Sam68可降低人SK-N-SH和SH-SY5Y NB细胞的增殖、迁移和侵袭。同样，miR-203的过表达也抑制了这两种细胞系的增殖、迁移和侵袭。进一步证明，在SK-N-SH和SH-SY5Y NB细胞中，miR-203负向调节Sam68的蛋白表达水平。此外，双荧光素酶报告基因检测数据证实，miR-203通过与其3'非翻译区结合直接靶向Sam68。总之，据我们所知，本研究首次表明，miR-203的异常下调可能导致NB中Sam68的异常上调，并且miR-203通过靶向Sam68对NB的恶性进展具有抑制作用。本研究为支持miR-203/Sam68作为NB的新型诊断或治疗靶点提供了证据。
