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Chansu is a traditional Chinese medicine that is generally recognized as a specific inhibitor of Na + /K + -ATPase. Bufalin, an active component of Chansu, is an endogenous steroid hormone with great potential as a cancer treatment. However, the mechanism by which it exerts its antitumor activity requires further research. Currently, the α1 subunit of Na + /K + -ATPase (ATP1A1) is known to exert important roles in tumorigenesis, and the precise mechanisms underlying the effect of Bufalin on the Na + /K + -ATPase α1 subunit was therefore investigated in this study to determine its role in glioblastoma treatments. The effect of ATP1A1 on the sensitivity of glioblastoma cells to Bufalin was investigated using MTT assays, RT-PCR and siRNA. Western blot was also used to explore the important roles of the ubiquitin-proteasome pathway in the Bufalin-mediated inhibition of ATP1A1. Xenografted mice were used to examine the anti-tumor activity of Bufalin in vivo . LC–MS/MS analysis was performed to determine the ability of Bufalin to traverse the blood-brain barrier (BBB). The results indicated that Bufalin inhibited the expression of ATP1A1 in glioblastoma by promoting the activation of proteasomes and the subsequent protein degradation of ATP1A1, while Bufalin had no effect on ATP1A1 protein synthesis. Bufalin also inhibited the expression of ATP1A1 in xenografted mice and significantly suppressed tumor growth. These data should contribute to future basic and clinical investigations of Bufalin. In conclusion, Bufalin significantly inhibited the expression of ATP1A1 in glioblastoma cells by activating the ubiquitin-proteasome signaling pathway. Bufalin may therefore have the potential to be an effective anti-glioma drug for human glioblastoma in the future. [ABSTRACT FROM AUTHOR]

RNA modification is an important form of regulation in cancer biology, that is capable of affecting cell proliferation, migration, other genetic characteristics of tumors, and protein expression. Recent research has shown that dysregulation of RNA modification plays an important role in glioma pathogenesis. A key form of RNA post-transcriptional modification, alternative polyadenylation (APA), may represent a mechanism by which genes escape miRNA-mediated inhibition of cancer. Global shortening of 3' untranslated region (3'-UTR)-mediated APA events have become a potential novel marker of cancer progression. Current treatments in which a single gene or pathway is targeted do not have significant therapeutic benefits for glioma patients, while strategies that are less targeted, in which inhibitors of major regulatory hubs such as APA regulators are utilized, may have superior therapeutic effects. However, the precise mechanisms by which untranslated region-alternative polyadenylation (UTR-APA) regulates glioma are poorly understood. In the present review, we will discuss the important roles of UTR-APA in glioma. In addition to the role of APA in the progression of glioma, we will also explore potential treatment options that target these processes to improve the prognosis of glioma patients. [Display omitted] • UTR-APA exerts various important effects on the regulation of glioma progression. • Various factors could regulate APA and 3'UTR length in the brain. • UTR-APA exerts important effects on various oncogenes during glioma tumorigenesis. • UTR-APA plays important roles in drug resistance in glioma treatment. [ABSTRACT FROM AUTHOR]