胰腺癌早期诊断困难、极易发生侵袭转移是其生存率低的主要原因。申请者研究发现胰腺癌中miR-301a高表达，能活化NF-kB信号通路参与胰腺癌的侵袭转移，抑制miR-301a能够抑制裸鼠移植瘤的生长。但miR-301a参与胰腺癌侵袭转移的分子机制尚不清楚。本研究拟在前期研究的基础上，首先检测有无淋巴结转移的胰腺癌患者血清和肿瘤组织中miR-301a及侵袭转移相关分子的表达差异，证实miR-301a与胰腺癌侵袭转移密切相关；进一步应用生物信息学和分子生物学技术寻找miR-301a特异性靶基因，并证实miR-301a通过直接靶向抑制侵袭转移相关分子（PTEN、PAR3、SOCS5）表达而促进胰腺癌的侵袭转移的分子机制，随后应用活体动物成像系统证实miR-301a能够调节胰腺癌侵袭转移，为胰腺癌侵袭转移的新的分子机制提供理论和实验依据，并为以miR-301a为靶治疗胰腺癌的实验研究提供新的策略。

Human pancreatic adenocarcinoma is a deadly malignancy with a 5-year survival rate of about 5%. The poor prognosis is due to the fact that pancreatic cancer is rarely found at an early stage and approximately 80% of newly diagnosed patients are already in the metastatic stage of the disease. MicroRNAs (miRNA) are a growing class of small, noncoding RNAs (20-25 nucleotides) that negatively regulate gene expression by targeting mRNAs for translational repression, degradation, or both. Research has shown that many miRNAs are involved in the development and prognosis prediction of a variety of tumors, as oncogenes or anti-oncogenes. Functional analyses suggest that miRNAs play roles in pancreatic cancer initiation, invasion and progression processes and, therefore, may prove to be informative biomarkers of detection, diagnosis and prognosis besides being potential targets of therapy. We have demonstrated that miR-301a down-regulates NF-kB-repressing factor (Nkrf) and elevates NF-kB activation. Moreover, miR-301a inhibition in pancreatic cancer cells led to reduced NF-kB target gene expression and attenuated xenograft tumor growth. In this work, we investigate whether miR-301a contribute to invasion and metastasis in pancreatic cancer by regulating relative gene expression. We demonstrate that miR-301a different expression in pancreatic cancer patients with or without lymph node or distant metastasis first, then we investigate the molecular mechanism of miR-301a involved in pancreatic cancer invasion and metastasis by down-regulate many molecules expression which relative with cancer invasion and metastasis. Revealing this novel mechanism by miR-301a offers new avenues for therapeutic interventions against pancreatic cancer.