Abstract
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.
Highlights
Introduction Long noncodingRNAs are noncoding chains of more than 200 ribonucleotides that play vital roles in various processes occurring in both normal and cancerous cells[1,2,3]
The results showed that inhibition of hypoxia-inducible factor (HIF)-1α expression in glioma cells with overexpression of NF-kappa B interacting lncRNA (NKILA) can effectively reverse the stimulation of the Warburg effect and angiogenesis in gliomas
NKILA acts as a tumor suppressor and inhibits metastasis in many other types of malignant cancers[34,35], we found that NKILA stimulates the Warburg effect and angiogenesis, may promote the cell proliferation in gliomas, and that increased expression of NKILA was correlated with decreased patient survival time
Summary
RNAs (lncRNAs) are noncoding chains of more than 200 ribonucleotides that play vital roles in various processes occurring in both normal and cancerous cells[1,2,3]. Recent research has shown that lncRNAs are abundantly expressed in human cells and frequently misregulated in malignant tumors. NF-kappa B interacting lncRNA (NKILA), which was identified in 2015, is upregulated by NF-kappa B and Gliomas are the most common malignant tumors of the human brain and are characterized by excessive proliferation, local invasion, high rates of recurrence, and poor prognoses[13,14]; gliomas seldom metastasize[14,15]. Understanding how NKILA functions in gliomas may be important. We found that NKILA is significantly upregulated in clinical glioma
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