蟾蜍毒素诱导miR-2110靶击FGFR1抑制鼻咽癌肿瘤干性、增殖和转移

miR-2110在鼻咽癌（NPC）中克隆，但在肿瘤中的作用尚不明确。我们前期发现miR-2110在NPC中表达下调，并作为抑癌候选基因调控PTEN/PI3K/AKT及下游肿瘤干性、细胞周期和EMT信号抑制NPC恶性表型。进一步我们观察到FGFR1是miR-2110潜在的靶基因，能与NEDD4结合并诱导其表达，导致PTEN泛素化降解。此外，蟾蜍毒素作为抗肿瘤中药成分，在NPC中可诱导miR-2110、下调FGFR1表达。后续研究将明确：蟾蜍毒素在NPC中抑制PI3K/AKT/c-Jun，诱导miR-2110表达，从而抑制FGFR1，降低与NEDD4结合并下调其表达，抑制PTEN泛素化，进而抑制PI3K/AKT及其下游肿瘤干性、细胞周期和EMT信号，最终抑制NPC细胞肿瘤干性、生长和转移。本研究不但揭示miR-2110靶击FGFR1抑制NPC恶性表型，且进一步揭示蟾蜍毒素抗肿瘤的崭新分子机理。

miR-2110 was cloned in nasopharyngeal carcinoma(NPC). However, its action was still undetermined in tumors. In the previous study, we observed that miR-2110 suppressed the malignant phenotypes via inactivating PTEN/PI3K/AKT and its downstream signals including tumor stemness, cell cycle, and EMT. Further, we found that FGFR1 was a potential targeted gene of miR-2110. It can bind to NEDD4 and induce its expression, which increased the ubiquitination of PTEN and stimulated its degradation. Furthermore, Toad venom as an anti-tumor component of Chinese medicine preparations upregulated the miR-2110 expression and decreased FGFR1 expression in NPC. In the futher investigation, we will confirm that Toad venom suppresses PI3K/AKT/c-Jun signal and thus upregulates miR-2110 expression. The latter will directly target FGFR1 to reduce its binding with NEDD4 and downregulate its expression, which thus reduces the ubiquitination of PTEN and suppressed its degradation. Increased PTEN will inactivate PI3K/AKT and its downstream signals including tumor stemness, cell cycle, and EMT and finally block tumor stemness, growth, and metastasis. Our study will not only deeply showed that miR-2110 targets FGFR1 suppressing malignant phenotypes of NPC, but further revealed a new anti-tumor molecular basis of Toad venom.