Long noncoding RNA KB-1460A1.5 inhibits glioma tumorigenesis via miR-130a-3p/TSC1/mTOR/YY1 feedback loop

Abstract Long noncoding RNAs (lncRNAs) have been shown to be closely related to cancer progression and therapy. However, the clinical significance of lncRNAs and the mechanisms by which they function in glioma are largely unknown. In this study, using online data sets combined with collected clinical glioma tissues, we determined that the lncRNA KB-1460A1.5 is downregulated and positively correlated with prognosis in glioma. Functional experiments showed that overexpression of KB-1460A1.5 inhibits glioma cell proliferation, migration and invasion in vitro and in vivo, while downregulation of KB-1460A1.5 has the opposite effects. Mechanistically, tandem mass tag (TMT)-based quantitative proteomic analysis revealed that KB-1460A1.5 preferentially affects the Akt/TSC1/mTOR pathway. KB-1460A1.5 was found to function as a competing endogenous RNA (ceRNA) to regulate the expression of TSC1, a key regulatory component of the mTOR pathway, by sponging miR-130a-3p in glioma cells. Furthermore, our data demonstrate that the mTOR pathway regulates the expression of the transcription factor Yin Yang 1 (YY1), which in turn binds directly to the KB-1460A1.5 promoter and affects the expression of KB-1460A1.5. Untargeted metabolomics and quantitative real-time PCR (qRT-PCR) analysis further confirmed the effects of KB-1460A1.5 on amino acid metabolism. In conclusion, this study revealed that lncRNA KB-1460A1.5 inhibits glioma tumorigenesis via miR-130a-3p/TSC1/mTOR/YY1 feedback loop.