宫颈腺癌发病率呈升高趋势，且患者生存期较鳞癌短，是宫颈癌治疗的难点，其进展机制亟待阐明。我们前期发现宫颈腺癌中miR-27a通过抑制TGF-ß通路受体和效应蛋白SMAD2/3发挥抑癌作用（鳞癌中无该机制），但其下游机制不明。最新研究发现SMAD2/3可介导特定基因mRNA发生m6A甲基化和降解；通过结构分析，我们发现m6A甲基化酶METTL14存在与SMAD2/3结合的特定基序；结合宫颈癌RNA测序和m6A RNA测序结果，筛选出腺癌中可能受SMAD2/3相关m6A调控的抑癌基因，并初步验证了miR-27a对这些基因m6A和表达的调控。据此我们提出：宫颈腺癌中miR-27a通过解除SMAD2/3募集m6A甲基转移酶介导的抑癌基因m6A修饰发挥抑癌作用。本项目旨在阐明宫颈腺癌中miR-27a对抑癌基因m6A修饰的调控作用和机制，探讨该机制对肿瘤进展的影响以及临床转化意义，为治疗提供新靶点。

Cervical adenocarcinoma (CADC) represents a difficalty in the management of cervical cancer because of the increasing incidence and poor survival. It is therefor urgent to clarify the mechanisms underlying disease progression. In a previous study, we have found that in CADC, but not in cervical squamous cell carcinoma, miR-27a inhibits tumor progression by downregulating TGF-ß receptor I (TGF-ßRI) and SMAD2/3, the key effective factors of TGF-ß pathway. However, the downstream mechnisms remain unclear. Recently, SMAD2/3 has been found to mediate mRNA methylation (m6A) and instability through cruiting m6A methyltransferase complex METTL4-METTL14-WTAP. Thus, we analyzed the protein structure of SMAD2/3 and METTL4-METTL14-WTAP and found a SMAD-interaction motif-similar sequence in the C'-end of METTL14. Moreover, based on RNA-seq data of human CADC and m6A MeRIP-seq data in cells with manipulated SMAD2/3, we identified several tumor suppressor genes that may be down-regulated by SMAD2/3-associated m6A in CADC and explored the role of miR-27a in the m6A modification of these tumor suppressor genes. Hereby, we hypothesize that miR-27a inhibits CADC propgression via relieving the SMAD2/3-associated m6A of tumor suppressor genes. The purpose of the present project is to clarify the role ofmiR-27a in m6A modification and the underlying molecular mechanisms and explore its involvement in CADC progression, that might provide novel targets for the treatment of patients with CADC.