FOXO1直接拮抗MYH9诱导miR-200b抑制鼻咽癌转移和肿瘤干性研究

我们初步发现FOXO1抑制鼻咽癌细胞转移和肿瘤干性维持。进一步，CoIP结合质谱分析以及外源性免疫共沉淀实验揭示MYH9为FOXO1在鼻咽癌中候选直接作用蛋白。除此之外，FOXO1还被发现诱导miR-200b表达，而MYH9则抑制其表达。我们推测，FOXO1在鼻咽癌中直接拮抗MYH9，通过相应信号通路诱导miR-200b表达，从靶击ZEB2、ZEB1和Bmi-1等EMT和干性相关基因，进而抑制鼻咽癌转移和肿瘤干性。进一步工作如下：明确FOXO1和MYH9分别抑制和诱导鼻咽癌转移和肿瘤干性以及它们具体分子机制；明确FOXO1直接拮抗MYH9，诱导miR-200b，抑制鼻咽癌转移和肿瘤干性以及放化疗增敏；明确FOXO1、MYH9和miR-200b在鼻咽癌中表达相关性以及临床进展和预后关系；我们的工作将首次报导抑癌核转录因子FOXO1通过直接拮抗胞浆蛋白MYH9，抑制鼻咽癌转移和肿瘤干性的维持。

We preliminarily observed that FOXO1 suppressed cell metastasis, and cancer stemness maintenance in nasopharyngeal carcinoma(NPC). Further, CoIP combinded with mass spectrography and exogenous co-immunoprecipitation assays revealed that MYH9 is a potentially direct interaction protein of FOXO1 in NPC. Furthermore, FOXO1 was observed to induce the expression of miR-200b and MYH9 was found to suppress the miR-200b expression in NPC. We speculated that FOXO1 directly antagonized MYH9 and induced the miR-200b, a tumor suppressive-miRNA that could directly target EMT and cancer stemness-related genes including ZEB2, ZEB1, and Bmi-1, by modulating corresponding signals, which blocked cell metastasis and cancer stemness maintenance in NPC. The further works are as followed: 1) Identifying the respectively detailed roles of FOXO1 and MYH9 in modulating the metastasis and cancer stemness maintenance as well as their specific molecular mechanism in NPC. 2) Confirming that FOXO1 directly antagonized MYH9, which further induced the expression of miR-200 suppressing cell metastasis and cancer stemness maintenance and increasing the sensitization of radiotherapy and chemotherapy in NPC. 3) Confirming the expression correlation of FOXO1, MYH9, and miR-200b and their roles in clinical progression and prognosis in NPC. Our work will firstly report that tumor-suppressive nucleus transcription factor FOXO1 directly antagonized cytoplasmic expression protein MYH9 suppressing cell metastasis and cancer stemness maintenance in NPC.