转移是胰腺癌患者治疗失败的主要原因，突出表明迫切需要有效的治疗策略。在这里，我们重点鉴定在胰腺癌转移中具有关键作用的新型 miRNA。对转移性和非转移性胰腺癌样本中 miRNA 表达的微阵列分析显示，转移性肿瘤组中 miR-6794-3p 的表达显着降低。使用分别表达低水平和高水平 miR-6794-3p 的胰腺癌细胞系 MIA-PaCa-2 和 HPAF-II 进行功能获得和功能丧失方法，表明 miR-6794-3p 在抑制细胞侵袭、迁移和 EMT 信号传导。重要的是，我们的结果表明 miR-6794-3p 通过抑制染色质重塑因子 RBBP4 的表达来发挥作用。由此产生的 RBBP4 抑制诱导 GRHL2 水平增加，GRHL2 参与调节转移性胰腺癌细胞的侵袭、迁移和 EMT 信号传导。与这些发现一致，低 miR-6794-3p 表达水平与胰腺癌患者生存率低相关。对裸鼠的额外临床前实验清楚地证明了 miR-6794-3p 对胰腺癌细胞转移的抑制作用。集体结果强调了 miR-6794-3p 作为转移抑制因子的功能意义，并支持其作为胰腺癌预后生物标志物和治疗靶点的预测效用。© 作者。

Metastasis is a major cause of treatment failure in patients with pancreatic cancer, highlighting the urgent need for effective therapeutic strategies. Here, we focused on identifying novel miRNAs with key roles in metastasis of pancreatic cancer. Microarray analysis of miRNA expression in metastatic and non-metastatic pancreatic cancer samples revealed significantly lower expression of miR-6794-3p in the metastatic tumor group. Gain- and loss-of-function approaches using the pancreatic cancer cell lines MIA-PaCa-2 and HPAF-II expressing low and high levels of miR-6794-3p, respectively, indicated a role of miR-6794-3p in suppression of cell invasion, migration, and EMT signaling. Importantly, our results showed that miR-6794-3p exerts its effects by inhibiting expression of the chromatin remodeling factor, RBBP4. The resulting suppression of RBBP4 induced an increase in the levels of GRHL2 involved in regulating invasion, migration, and EMT signaling in metastatic pancreatic cancer cells. Consistent with these findings, low miR-6794-3p expression levels correlate with poor pancreatic cancer patient survival. Additional preclinical experiments on nude mice clearly demonstrated inhibitory effects of miR-6794-3p on pancreatic cancer cell metastasis. The collective results highlight the functional significance of miR-6794-3p as a suppressor of metastasis and support its predictive utility as a prognostic biomarker and therapeutic target in pancreatic cancer.© The author(s).