PIWI (P element induced wimpy testis) integrating RNAs (piRNAs) are small non-coding RNAs with the length of approximately 30 nucleotides that plays crucial roles in germ cells and adult stem cells. Recently, accumulating data have shown that piRNA and PIWI proteins are involved in tumorigenesis. However, the roles of PIWI proteins and piRNAs in pancreatic cancer are still elusive. Here, we showed that piR-017061 is significantly downregulated in pancreatic cancer patients’ samples and pancreatic cancer cell lines. Furthermore, we studied the function of piR-017061 in pancreatic cancer and our data revealed that piR-017061 inhibits pancreatic cancer cell growth in vitro and in vivo. Moreover, we analyzed the genomic loci around piR-017061 and identified EFNA5 as a novel target of piR-017061. Importantly, our data further revealed a direct binding between piR-017061 and EFNA5 mRNA mediated by PIWIL1. Mechanically, piR-017061 cooperates with PIWIL1 to facilitate EFNA5 mRNA degradation and loss of piR-017061 results in accumulation of EFNA5 which facilitates pancreatic cancer development. Hence, our data provided novel insights into PIWI/piRNA-mediated gene regulation and their function in pancreatic cancer. Since PIWI proteins and piRNA predominately express in germline and cancer cells, our study provided novel therapeutic strategy for pancreatic cancer treatment.

PIWI（P 元件诱导的小睾丸）整合 RNA (piRNA) 是长度约为 30 个核苷酸的小型非编码 RNA，在生殖细胞和成体干细胞中起着至关重要的作用。最近，越来越多的数据表明 piRNA 和 PIWI 蛋白参与了肿瘤的发生。然而，PIWI 蛋白和 piRNAs 在胰腺癌中的作用仍然难以捉摸。在这里，我们发现 piR-017061 在胰腺癌患者的样本和胰腺癌细胞系中显着下调。此外，我们研究了 piR-017061 在胰腺癌中的功能，我们的数据显示 piR-017061 在体外和体内抑制胰腺癌细胞的生长。此外，我们分析了 piR-017061 周围的基因组位点，并将 EFNA5 鉴定为 piR-017061 的新靶点。重要的，我们的数据进一步揭示了 PIWIL1 介导的 piR-017061 和 EFNA5 mRNA 之间的直接结合。在机械上，piR-017061 与 PIWIL1 协同促进 EFNA5 mRNA 降解，piR-017061 的缺失导致 EFNA5 的积累，从而促进胰腺癌的发展。因此，我们的数据为 PIWI/piRNA 介导的基因调控及其在胰腺癌中的功能提供了新的见解。由于 PIWI 蛋白和 piRNA 主要在生殖系和癌细胞中表达，我们的研究为胰腺癌的治疗提供了新的治疗策略。我们的数据为 PIWI/piRNA 介导的基因调控及其在胰腺癌中的功能提供了新的见解。由于 PIWI 蛋白和 piRNA 主要在生殖系和癌细胞中表达，我们的研究为胰腺癌的治疗提供了新的治疗策略。我们的数据为 PIWI/piRNA 介导的基因调控及其在胰腺癌中的功能提供了新的见解。由于 PIWI 蛋白和 piRNA 主要在生殖系和癌细胞中表达，我们的研究为胰腺癌的治疗提供了新的治疗策略。