Department of Neurosurgery, XinHua Hospital, Shanghai JiaoTong University School of Medicine, 1665 KongJiang Rd, Shanghai, 200092, China.
The Cranial Nerve Disease Center of Shanghai JiaoTong University, Shanghai, 200092, China.
Cell Death Dis. 2020 May 7;11(5):323. doi: 10.1038/s41419-020-2520-2.
In various malignant tumors, NF-kappa B interacting long noncoding RNA (NKILA) displays antitumor activity by inhibiting the NF-kappa B pathway. However, the role of NKILA in gliomas remains unclear. Surprisingly, this study showed that NKILA is significantly upregulated in gliomas, and the increased levels of NKILA were correlated with a decrease in patient survival time. NKILA increased the expression level of hypoxia-inducible factor-1α, and the activity of the hypoxia pathway in gliomas. Furthermore, we demonstrated that NKILA enhances the Warburg effect and angiogenesis in gliomas both in vitro and in vivo. Therefore, NKILA is a potential therapeutic target in gliomas. In addition, we showed that a 20(S)-Rg3 monomer suppresses NKILA accumulation and reverses its stimulation of the Warburg effect and angiogenesis in gliomas, both in vitro and in vivo. Therefore, this study not only identified NKILA as a potential therapeutic target in gliomas, but also demonstrated a practical approach to treatment.
在各种恶性肿瘤中，NF-κB 相互作用的长非编码 RNA（NKILA）通过抑制 NF-κB 通路显示出抗肿瘤活性。然而，NKILA 在神经胶质瘤中的作用尚不清楚。令人惊讶的是，本研究表明 NKILA 在神经胶质瘤中显著上调，NKILA 水平的增加与患者生存时间的减少相关。NKILA 增加了缺氧诱导因子-1α的表达水平，以及神经胶质瘤中缺氧通路的活性。此外，我们证明 NKILA 增强了神经胶质瘤的瓦伯格效应和血管生成，无论是在体外还是体内。因此，NKILA 是神经胶质瘤的一个潜在治疗靶点。此外，我们表明，20(S)-Rg3 单体抑制 NKILA 的积累，并逆转其对神经胶质瘤中瓦伯格效应和血管生成的刺激，无论是在体外还是体内。因此，本研究不仅鉴定了 NKILA 作为神经胶质瘤的一个潜在治疗靶点，还证明了一种实用的治疗方法。
