Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Operating Room, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
J Cell Biochem. 2018 Nov;119(11):9081-9089. doi: 10.1002/jcb.27167. Epub 2018 Jun 28.
Glioblastoma (GBM) is a devastating and highly aggressive tumor, which is apoptosis resistant and difficult to cure. Recently, long noncoding RNAs have been shown to play a pivotal role in GBM progression. Evidence has suggested that retinal noncoding RNA3 (RNCR3) is a GBM-associated noncoding RNA and is under-expressed in GBM. However, the function and mechanism of RNCR3 on GBM cell growth and apoptosis are still uncertain. In the current study, we found that the level of RNCR3 is decreased in U87, U251, U373, and A172 GBM cell lines when compared with the normal human astrocytes. Elevating long noncoding RNA RNCR3 expression markedly inhibits U87 and U251 cell survival and proliferation. Further studies indicated that RNCR3 overexpression promotes U87 and U251 cell apoptosis and activity caspase-3/7. Moreover, we found that RNCR3 overexpression promotes Krüppel-like factor 16 (KLF16) expression through inhibiting the level of miR-185-5p. We demonstrated that KLF16 is a direct target of miR-185-5p. An increased miR-185-5p level by a miR-185-5p mimic or decreased KLF16 by KLF16 small interfering RNA both reversed the function of RNCR3 overexpression on GBM cell growth and apoptosis. In summary, this study focuses on investigating the key molecular mechanisms of RNCR3 involved in GBM cell growth and apoptosis. Our data indicated that RNCR3 overexpression inhibits cell growth and induces its apoptosis through the miR-185-5p/KLF16 axis.
胶质母细胞瘤（GBM）是一种具有破坏性且高度侵袭性的肿瘤，其具有抗细胞凋亡的特性，难以治愈。最近，长链非编码 RNA 已被证明在 GBM 进展中发挥关键作用。有证据表明，视网膜非编码 RNA3（RNCR3）是一种与 GBM 相关的非编码 RNA，在 GBM 中表达下调。然而，RNCR3 对 GBM 细胞生长和凋亡的功能和机制仍不清楚。在本研究中，我们发现与正常的人类星形胶质细胞相比，U87、U251、U373 和 A172 GBM 细胞系中 RNCR3 的水平降低。上调长链非编码 RNA RNCR3 的表达显著抑制 U87 和 U251 细胞的存活和增殖。进一步的研究表明，RNCR3 过表达促进 U87 和 U251 细胞的凋亡和活性 caspase-3/7。此外，我们发现 RNCR3 过表达通过抑制 miR-185-5p 的水平促进 Krüppel 样因子 16（KLF16）的表达。我们证明 KLF16 是 miR-185-5p 的直接靶标。miR-185-5p 模拟物增加 miR-185-5p 水平或 KLF16 小干扰 RNA 降低 KLF16 水平均可逆转 RNCR3 过表达对 GBM 细胞生长和凋亡的作用。总之，本研究重点研究了 RNCR3 参与 GBM 细胞生长和凋亡的关键分子机制。我们的数据表明，RNCR3 过表达通过 miR-185-5p/KLF16 轴抑制细胞生长并诱导其凋亡。
