Since the breakthrough discoveries of DNA and histone modifications, the field of RNA modifications has gained increasing interest in the scientific community. The discovery of N6-methyladenosine (m6A), a predominantly internal epigenetic modification in eukaryotes mRNA, heralded the creation of the field of epi-transcriptomics. This post-transcriptional RNA modification is dynamic and reversible, and is regulated by methylases, demethylases and proteins that preferentially recognize m6A modifications. Altered m6A levels affect RNA processing, degradation and translation, thereby disrupting gene expression and key cellular processes, ultimately resulting in tumor initiation and progression. Furthermore, inhibitors and regulators of m6A-related factors have been explored as therapeutic approaches for treating cancer. In the present review, the mechanisms of m6A RNA modification, the clinicopathological relevance of m6A alterations, the type and frequency of alterations and the multiple functions it regulates in different types of cancer are discussed.
N6-methyladenosine (m6A) is the most commonly occurring internal RNA modification to be found in eukaryotic mRNA and serves an important role in various physiological events. AlkB homolog 5 RNA demethylase (ALKBH5), an m6A demethylase, belongs to the AlkB family of dioxygenases and has been shown to specifically demethylate m6A in RNA, which is associated with a variety of tumors. However, its function in bladder cancer remains largely unclear. In the present study, we found that the expression of ALKBH5 was downregulated in bladder cancer tissues and cell lines. Low expression of ALKBH5 was correlated with the worse prognosis of bladder cancer patients. Furthermore, functional assays revealed that knockdown of ALKBH5 promoted bladder cancer cell proliferation, migration, invasion, and decreased cisplatin chemosensitivity in the 5637 and T24 bladder cancer cell lines in vivo and in vitro , whereas ALKBH5 overexpression led to the opposite results. Finally, ALKBH5 inhibited the progression and sensitized bladder cancer cells to cisplatin through a casein kinase 2 (CK2)α-mediated glycolysis pathway in an m6A-dependent manner. Taken together, these findings might provide fresh insights into bladder cancer therapy.
Neutrophil infiltration is frequently observed in lung cancer tissues. Extracellular RNAs (exRNAs) may facilitate tumor progression. The present study investigated the cross-talk of tumor exRNAs and neutrophil extracellular traps (NETs) in lung cancer. Lewis lung carcinoma (LLC) cells were cultured with the deprived sera. And the cell culture supernatants (CCS) were analyzed in vitro and in vivo . The results revealed that exRNAs from lung cancer CCS promoted the inflammatory cytokine interleukin-1β and reduced the vascular cell adhesion molecule-1 expression in lung epithelial cells. Lung cancer CCS-treated epithelial cells induced the production of NETs. By contrast, NETs reduced the tight junction protein claudin-5 in epithelial cells. Furthermore, NETs caused the necrosis of epithelial cells, which resulted in the release of exRNAs. In mice, lung cancer cells instilled in the lung recruited neutrophils and initiated NETs. In patients with lung cancer, NETs were also observed. These results suggested that exRNAs in the cell culture supernatant may indirectly induce NETs and contribute to lung cancer oncogenesis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.