Department of Neurosurgery, the Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi 214023, PR China.
Technol Cancer Res Treat. 2012 Oct;11(5):483-90. doi: 10.7785/tcrt.2012.500264. Epub 2012 May 7.
Tumor stem cells (TSCs) have been identified in many malignant tumors and are unique in their self-renewal, multi-differentiation and tumor growth maintenance capabilities. MicroRNAs (miRNAs) are small endogenous, non-coding RNAs that predominately modulate target gene expression at the post-transcriptional level. Accumulating evidence suggests that some miRNAs have an essential role in TSC proliferation, growth, apoptosis, and differentiation. In particular, miR-34a has been found to inhibit proliferation and induce apoptosis in stem cells. The insensitivity of glioma to standard therapies combined with the hypothesis that glioma stem cells (GSCs) are responsible for this chemorefractory nature suggests that investigations exploring the function and mechanism of miR-34a in GSCs would be of value. In our study, we found that miR-34a is down-regulated in CD133-positive U87 cells. Furthermore, miR-34a could significantly suppress cell proliferation and induce apoptosis in GSCs. These findings suggest that miR-34a acts as a tumor suppressor in U87 GSCs. Therefore, this observation highlights a new potential therapeutic agent for GSC-based glioma treatment.
肿瘤干细胞（TSCs）已在许多恶性肿瘤中被鉴定出来，其自我更新、多向分化和肿瘤生长维持能力具有独特性。微小 RNA（miRNA）是小的内源性非编码 RNA，主要在转录后水平调节靶基因的表达。越来越多的证据表明，一些 miRNA 在 TSC 的增殖、生长、凋亡和分化中发挥着重要作用。特别是 miR-34a 已被发现可抑制干细胞的增殖并诱导其凋亡。由于胶质瘤对标准治疗不敏感，再加上假设胶质瘤干细胞（GSCs）是导致这种化疗耐药的原因，这表明探索 miR-34a 在 GSCs 中的功能和机制的研究将具有价值。在我们的研究中，我们发现 miR-34a 在 CD133 阳性的 U87 细胞中下调。此外，miR-34a 可显著抑制 GSCs 的细胞增殖并诱导其凋亡。这些发现表明 miR-34a 在 U87 GSCs 中作为肿瘤抑制因子发挥作用。因此，这一观察结果突出了一种基于 GSC 的治疗胶质瘤的新的潜在治疗药物。
