长链非编码RNA H19可能通过直接转录miR-675表达调控多种人类肿瘤的发生发展，影响肿瘤细胞的生物学行为，但其与胰腺肿瘤干细胞的相关性研究未见报道。本研究前期工作表明：H19在胰腺癌组织中高表达且与miR-675的表达水平正相关；调控H19的表达水平可影响胰腺癌细胞增殖能力及CD24+CD44+ESA+肿瘤干细胞比例；进一步研究发现H19/miR-675参与调控胰腺癌Panc-1细胞EMT过程及体外成球能力。本研究拟在此基础上，通过沉默或过表达H19/miR-675关键基因的水平，探讨H19/miR-675对胰腺癌细胞EMT和干细胞化过程的调控机制；评价其与临床病理特征的相关性，探讨其在预测患者化疗敏感性、肿瘤复发、远处转移、预后等方面的作用；阐明H19/miR-675通过介导EMT和多能性转录因子的表达水平，调控肿瘤干细胞化的机制，为其作为靶点的临床应用提供理论依据及实践基础。

The long non-coding RNA H19 regulates various signaling pathways via miR-675 in embryonic development. Studies have shown that H19/miR-675 was critical in regulating tumorigenesis and affecting the malignant behaviors in many kinds of human malignancies. However, the effects and mechanisms of H19/miR-675 on the cancer stem cells in human pancreatic cancer has not been elucidated. Our previous studies showed that H19 was highly expressed in human pancreatic cancer cells, and it is positively correlated with miR-675 expression level. The expression levels of H19 in pancreatic cancer cell lines were correlated with the proliferation ability, the proportion of CD24+CD44+ESA+ cancer stem cells, and the chemosensitivity to gemcitabine. Furthermore, H19/miR-675 was found to be involved in the regulation of Epithelial-Mesenchymal Transition (EMT) process as well as the cancer stem cell transformation in pancreatic cancer cells. In this study, we will explore the possible mechanisms of H19/miR-675 on modulating the EMT process and maintenance of cancer stem-like cells in human pancreatic cancer cells through silencing or overexpressing the key gene of H19/miR-675 signaling in vitro and in vivo. The expression levels of H19 and miR-675 in both resected cancer tissues and the serum from pancreatic cancer patients would be detected, and their relationship of H19/miR-675 and the clinical data will be analyzed to figure out their clinical significance. The aim of this study is to elucidate the mechanisms of H19/miR-675 on regulating the stemness of pancreatic cancer cells via inducing EMT process and modulating the pluripotency transcription factors expression, and to assess the value of H19/miR-675 as a therapeutic target of pancreatic cancer.