RESUMO
The N6-methyladenosine (m6A) modification possesses new and essential roles in tumor initiation and progression by regulating mRNA biology. However, the role of aberrant m6A regulation in nasopharyngeal carcinoma (NPC) remains unclear. Here, through comprehensive analyses of NPC cohorts from the GEO database and our internal cohort, we identified that VIRMA, an m6A writer, is significantly upregulated in NPC and plays an essential role in tumorigenesis and metastasis of NPC, both in vitro and in vivo. High VIRMA expression served as a prognostic biomarker and was associated with poor outcomes in patients with NPC. Mechanistically, VIRMA mediated the m6A methylation of E2F7 3'-UTR, then IGF2BP2 bound, and maintained the stability of E2F7 mRNA. An integrative high-throughput sequencing approach revealed that E2F7 drives a unique transcriptome distinct from the classical E2F family in NPC, which functioned as an oncogenic transcriptional activator. E2F7 cooperated with CBFB-recruited RUNX1 in a non-canonical manner to transactivate ITGA2, ITGA5, and NTRK1, strengthening Akt signaling-induced tumor-promoting effect.
Assuntos
Carcinogênese , Fator de Transcrição E2F7 , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Proteínas de Ligação a RNA , Humanos , Carcinogênese/genética , Transformação Celular Neoplásica , Fator de Transcrição E2F7/genética , Fator de Transcrição E2F7/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , RNA Mensageiro/genética , Proteínas de Ligação a RNA/metabolismo , Regulação para CimaRESUMO
As the most predominant RNA epigenetic regulation in eukaryotic cells, N6-methyladenosine (m6A) plays a critical role in human tumorigenesis and cancer progression. However, the biological function and molecular mechanism of m6A regulation in naso-pharyngeal carcinoma (NPC) remain elusive. Here, we showed that Wilms' tumor 1-associating protein (WTAP) expression was apparently upregulated in NPC, and increased WTAP was associated with poor prognosis. WTAP upregulated in NPC was fine-tuned by KAT3A-mediated H3K27 acetylation. Functionally, WTAP was required for the growth and metastasis of NPC. Mechanistically, lncRNA DIAPH1-AS1 was identified as a bona fide m6A target of WTAP. WTAP-mediated m6A modification of DIAPH1-AS1 enhanced its stability relying on the m6A reader IGF2BP2-dependent pathway. Furthermore, DIAPH1-AS1 acted as a molecular adaptor that promoted MTDH-LASP1 complex formation and upregulated LASP1 expression, ultimately facilitating NPC growth and metastasis. Thus, WTAP-mediated DIAPH1-AS1 m6A methylation is required for NPC tumorigenesis and metastasis.
Assuntos
Adenosina/análogos & derivados , Proteínas de Ciclo Celular , Forminas , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Fatores de Processamento de RNA , RNA Longo não Codificante , Proteínas Adaptadoras de Transdução de Sinal , Adenosina/genética , Adenosina/metabolismo , Carcinogênese , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Epigênese Genética , Forminas/genética , Forminas/metabolismo , Humanos , Proteínas com Domínio LIM/genética , Proteínas com Domínio LIM/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Metástase Neoplásica , Fatores de Processamento de RNA/genética , Fatores de Processamento de RNA/metabolismo , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
An optical image encryption technique based on compressive sensing using fully optical means has been proposed. An object image is first encrypted to a white-sense stationary noise pattern using a double random phase encoding (DRPE) method in a Mach-Zehnder interferometer. Then, the encrypted image is highly compressed to a signal using single-pixel compressive holographic imaging in the optical domain. At the receiving terminal, the encrypted image is reconstructed well via compressive sensing theory, and the original image can be decrypted with three reconstructed holograms and the correct keys. The numerical simulations show that the method is effective and suitable for optical image security transmission in future all-optical networks because of the ability of completely optical implementation and substantially smaller hologram data volume.
