Zhou Yu, Liu Yang, Hu Chao, Jiang Yugang
Department of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
Department of Rehabilitation, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
Int J Mol Med. 2016 Dec;38(6):1768-1776. doi: 10.3892/ijmm.2016.2775. Epub 2016 Oct 17.
MicroRNAs (miRNAs or miRs), a class of non-coding RNAs 18-25 nucleotides in length, act as key regulators in the development and malignant progression of various human cancers by modulating the expression of their target genes. Recently, miR‑16 has been demonstrated to be play a role in glioma. However, the regulatory mechanisms of miR‑16 in glioma growth and metastasis remain largely unclear. In the present study, qRT-PCR revealed that miR‑16 was significantly downregulated in 23 glioma tissue specimens compared to 7 normal brain tissue specimens. Moreover, its levels were markedly lower in the glioma samples at stages T2-T4 compared to those at stage T1. The overexpression of miR-16 significantly suppressed the proliferation, migration and invasion of U251 and U87 glioma cells. Luciferase reporter assay identified Sal-like protein 4 (SALL4) as a target gene of miR‑16, and its protein levels were found to be decreased in miR‑16-overexpressing U251 and U87 cells. Furthermore, the overexpression of SALL4 significantly reversed the suppressive effects of miR‑16 on the proliferation, migration and invasion of U251 and U87 cells, suggesting that miR‑16 playsa tumor suppressor role in glioma by inhibiting cell proliferation and invasion through the targeting of SALL4. Finally, we found that SALL4 was significantly upregulated in glioma tissues compared to normal brain tissues, and its levels were markedly higher in the glioma tissues at stages T2-T4 compared to those at stage T1. In addition, the expression levels of SALL4 inversely correlated with the miR‑16 levels in glioma tissues, suggesting that the downregulation of miR‑16 contributes to the upregulation of SALL4 in glioma. On the whole, the findings of this study indicate a role for the miR‑16/SALL4 axis in glioma. Our data may also provide a potential therapeutic target for the treatment of glioma.
微小RNA（miRNA或miR）是一类长度为18 - 25个核苷酸的非编码RNA，通过调节其靶基因的表达，在多种人类癌症的发生发展和恶性进展中发挥关键调控作用。最近，已证实miR-16在胶质瘤中发挥作用。然而，miR-16在胶质瘤生长和转移中的调控机制仍不清楚。在本研究中，qRT-PCR显示，与7个正常脑组织标本相比，23个胶质瘤组织标本中miR-16显著下调。此外，与T1期的胶质瘤样本相比，T2 - T4期的胶质瘤样本中其水平明显更低。miR-16的过表达显著抑制了U251和U87胶质瘤细胞的增殖、迁移和侵袭。荧光素酶报告基因检测确定类Sal蛋白4（SALL4）为miR-16的靶基因，并且发现在过表达miR-16的U251和U87细胞中其蛋白水平降低。此外，SALL4的过表达显著逆转了miR-16对U251和U87细胞增殖、迁移和侵袭的抑制作用，表明miR-16通过靶向SALL4抑制细胞增殖和侵袭，在胶质瘤中发挥肿瘤抑制作用。最后，我们发现与正常脑组织相比，胶质瘤组织中SALL4显著上调，并且与T1期的胶质瘤组织相比，T2 - T4期的胶质瘤组织中其水平明显更高。此外，胶质瘤组织中SALL4的表达水平与miR-16水平呈负相关，表明miR-16的下调促成了胶质瘤中SALL4的上调。总体而言，本研究结果表明miR-16/SALL4轴在胶质瘤中发挥作用。我们的数据也可能为胶质瘤的治疗提供一个潜在的治疗靶点。
