最近的研究表明，近百的调节蛋白(AREG)是表皮生长因子(EGF)家族的成员，表达于许多癌症中，并且是胰腺癌患者的独立预后指标，然而AREG是否在表观遗传水平上调控以促进胰腺癌(PC)的发展尚未解明。我们的研究结果支持AREG在胰腺癌组织和细胞系中高表达的观点。从功能上来说，AREG的缺失阻碍了胰腺癌(PC)细胞的增殖、迁移和侵袭。此外，我们通过测序鉴定和验证了甲基转移酶类似物3(METTL3)诱导AREG上的m6A修饰并促进AREG mRNA的稳定性。此外，我们获得了实验证据，证明miR-33a-3p通过miRDB和RNAinter的预测，靶向并抑制了METTL3的作用。修复实验表明miR-33a-3p通过METTL3抑制PC的进展。总之，这项研究揭示了miR-33a-3p通过靶向METTL3抑制m6A诱导AREG的稳定，从而在PC的侵袭性进展中发挥关键作用。AREG可能是PC治疗的潜在靶点。© 2023 Springer Nature Limited.

Recent studies have shown that amphoteric regulatory protein (AREG), a member of the epidermal growth factor (EGF) family, is expressed in many cancers and is an independent prognostic indicator for patients with pancreatic cancer, but whether AREG is regulated at the epigenetic level to promote the development of pancreatic cancer (PC) has not been elucidated. Our results support the notion that AREG is overexpressed in pancreatic cancer tissues and cell lines. Functionally, the deletion of AREG impedes pancreatic cancer (PC) cell proliferation, migration, and invasion. In addition, we identified and validated that methyltransferase-like 3 (METTL3) induced the m6A modification on AREG and facilitated the stability of AREG mRNA after sequencing. Additionally, we obtained experimental evidence that miR-33a-3p targets and inhibits METTL3 from taking action, as predicted by using the miRDB and RNAinter. Remediation experiments showed that miR-33a-3p inhibits PC progression through METTL3. In summary, this research reveals that miR-33a-3p inhibits m6A-induced stabilization of AREG by targeting METTL3, which plays a key role in the aggressive progression of PC. AREG could be a potential target for PC treatment.© 2023. Springer Nature Limited.