No abstract

Modification of m6A, as the most abundant mRNA modification, plays diverse roles in various biological processes in eukaryotes. Emerging evidence has revealed that m6A modification is closely associated with the activation and inhibition of tumor pathways, and it is significantly linked to the prognosis of cancer patients. Aberrant reduction or elevated expression of m6A regulators and of m6A itself have been identified in numerous tumors. In this review, we give a description of the dynamic properties of m6A modification regulators, such as methyltransferases, demethylases, and m6A binding proteins, and indicate the value of the balance between these proteins in regulating the expression of diverse genes and the underlying effects on cancer development. Furthermore, we summarize the “dual-edged weapon” role of RNA methylation in tumor progression and discuss that RNA methylation can not only result in tumorigenesis but also lead to suppression of tumor formation. In addition, we summarize the latest research progress on small-molecule targeting of m6A regulators to inhibit or activate m6A. These studies indicate that restoring the balance of m6A modification via targeting specific imbalanced regulators may be a novel anti-cancer strategy.

No abstract

Neuroblastoma (NB), an embryonic tumour originating from sympathetic crest cells, is the most common extracranial solid tumour type in children with poor overall prognosis. Accumulating evidence has demonstrated the involvement of long non-coding RNA (lncRNA) in numerous biological processes and their associations with embryonic development and multiple diseases. Ectopic lncRNA expression is linked to malignant tumours. Previous studies by our team indicate that MEG3 attenuates NB autophagy through inhibition of FOXO1 and epithelial-mesenchymal transition via the mTOR pathway in vitro. Moreover, MEG3 and EZH2 negatively regulate each other. In present study, we first collected 60 NB tissues and 20 adjacent tissues for Quantitative real-time polymerase chain reaction (Q-PCR) experiments and performed clinical correlation analysis of the results. At the same time, nude mice were used for subcutaneous tumour formation to detect the effect of MEG3 in vivo. Two NB cell lines, SK-N-AS and SK-N-BE(2)C, were overexpressed MEG3 and rescued with EZH2 and then were subjected to proliferation, migration, invasion, apoptosis and autophagy experiments. RNA-binding protein immunoprecipitation (RIP) and Co-Immunoprecipitation (Co-IP) experiments were performed to explore the molecular mechanism of MEG3 and EZH2 interaction. Q-PCR revealed that MEG3 expression was negatively correlated with INSS stage and risk grade of NB. Moreover, MEG3 overexpression was associated with inhibition of NB growth in vivo. MEG3 exerted an anti-cancer effect via stimulatory effects on EZH2 ubiquitination leading to its degradation. Conversely,

No abstract

No abstract

No abstract

Increasing evidence indicates that long non-coding RNA (lncRNA) is one of the most important RNA regulators in the pathogenesis of neuroblastoma (NB). However, limited studies have addressed the possibility that lncRNAs possess the ability of encoding functional peptides, which could affect the initiation and development of tumors by participating in signal pathway transduction, immune regulation, and tumor metabolism. Here, we found that downregulation of lncRNA FAM201A was associated with NB malignant progression and a poor prognosis. A variety of gain- and loss-of-function studies elucidated the anti-tumor effects of lncFAM201A on the regulation of growth and metastasis of NB cells. Surprisingly, combined with database predictions and experimental verifications, we found that significantly down-regulating lncRNA FAM201A in NB identified the ability to encode the tumor-suppressing micropeptide, NBASP, which negatively regulated the expression of FABP5. Mechanistically, our transcriptomics analyses confirmed that the regulatory role between NBASP and FABP5 was mediated by activation of the ERK pathway. In conclusion, our findings revealed that NBASP encoded by lncRNA FAM201A played a tumor-suppressor role in NB carcinogenesis via down-regulating FABP5 to inactivate the ERK pathway. These results extended our understanding of the relationship of lncRNA-encoded functional peptides and plasticity of tumor progression.