miR-644a靶向调控PITX2表达对食管鳞癌细胞放化疗敏感性的影响及其分子机制研究

PITX2 have been reported to be associated with the development and progression of several human cancers. Our previous study have elucidated that high PITX2 was closely associated with chemoradioresistance in human esophageal squamous cell carcinoma (ESCC). However, the exact mechanism of PITX2 overexpression in human ESCC is largely unknown. miRNAs (miRNA) are endogenous non-coding short RNAs, which could regulate a variety of process. Our study first found that miR-644a could target directly PITX2, which might involved in the regulation of chemoradioresistance in human ESCC. In this study, we tried to identify the relationship of miR-644a, PITX2 and its target genes with ESCC chemoradiotherapy sensitivity and the underlying mechanism involved, and summarize the high risk of biomarker closely related to the ESCC chemoradioresistance, providing some references for clinical treatment in the future.

PITX2已被发现与多种肿瘤中的发生发展关系密切。本课题组前期实验发现PITX2高表达与食管鳞癌患者放化疗抵抗性密切相关。但是PITX2在食管癌中过表达的机理尚未完全阐明。miRNA是一类内源性，非编码短链RNA，参与多种生物学功能。课题组通过预实验发现miR-644a靶向PITX2参与诱导食管癌细胞放化疗抵抗性的可能性。本项目通过基因表达调控，细胞实验，动物模型及人体食管癌组织标本探讨miR-644a, PITX2及其下游靶基因与食管癌放化疗敏感性的关系和作用机制，分析和总结与食管癌患者放化疗有关的高危的分子指标，为今后临床治疗提供参考。

PITX2已被发现与多种肿瘤中的发生发展关系密切。本课题组前期实验发现PITX2高表达与食管鳞癌患者放化疗抵抗性密切相关。但是PITX2在食管癌中过表达的机理尚未完全阐明。课题组通过预实验发现miR-644a靶向PITX2参与诱导食管癌细胞放化疗抵抗性的可能性。我们通过分子、细胞、整体水平的研究及临床样本的验证中，发现miR-644a在食管癌中广泛下调，且低表达与食管癌差预后显著相关，miR-644a能够抑制PITX2表达，从而激活信号通路诱导食管癌肿瘤干细胞活性及侵袭能力，分析和总结与食管癌患者放化疗有关的高危的分子指标，为今后临床治疗提供参考。同时我们筛选到miR-939, SLC34A2,GNA13等多个分子标记物在肿瘤中异常表达，并且促进肿瘤发生发展的分子机制，对于在临床决策中筛选复发、转移高危的患者，提前采用综合治疗延缓肿瘤的复发和转移，有重要的临床实践指导意义。