Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Cell Death Dis. 2018 Sep 20;9(10):940. doi: 10.1038/s41419-018-0965-3.
Long non-coding RNAs (lncRNAs) play crucial roles in the pathogenesis of pancreatic ductal adenocarcinoma (PDAC). Previously, we found that melittin treatment suppressed PDAC tumor growth. However, it is unclear whether lncRNAs have any role in the melittin-induced suppression of PDAC. In this study, we used microarray data to identify 844 lncRNAs that were significantly differentially expressed in response to melittin treatment. Of these lncRNAs, we focused on the lncRNA NONHSAT105177, which had about a 22-fold increase in expression with melittin treatment. We found that melittin treatment increased NONHSAT105177 expression in PDAC cell lines but not in normal pancreatic ductal epithelial cell line. NONHSAT105177 expression was significantly lower in PDAC cancer tissues than in adjacent noncancerous tissues. Additionally, overexpression of NONHSAT105177 inhibited PDAC cell proliferation, migration, and the epithelial-mesenchymal transition (EMT), both in vitro and in vivo. Consistent with the mechanism of action of melittin, NONHSAT105177 significantly downregulated cholesterol pathway genes, including Clusterin (CLU). Moreover, we found that NONHSAT105177 trafficking was mediated by exosomes. The combined findings of our current and previous studies suggest that NONHSAT105177 mediated the melittin-induced inhibition of PDAC cell growth and metastasis, which indicated a potential target for developing new strategies.
长链非编码 RNA（lncRNA）在胰腺导管腺癌（PDAC）的发病机制中发挥着关键作用。先前，我们发现蜂毒素治疗可抑制 PDAC 肿瘤生长。然而，lncRNA 是否在蜂毒素诱导的 PDAC 抑制中发挥作用尚不清楚。在这项研究中，我们使用微阵列数据鉴定了 844 个在蜂毒素处理后表达显著差异的 lncRNA。在这些 lncRNA 中，我们专注于 lncRNA NONHSAT105177，其表达在蜂毒素处理后增加了约 22 倍。我们发现蜂毒素处理可增加 PDAC 细胞系而非正常胰腺导管上皮细胞系中的 NONHSAT105177 表达。NONHSAT105177 在 PDAC 癌组织中的表达明显低于相邻非癌组织。此外，NONHSAT105177 的过表达抑制了 PDAC 细胞在体外和体内的增殖、迁移和上皮-间充质转化（EMT）。与蜂毒素的作用机制一致，NONHSAT105177 显著下调了胆固醇途径基因，包括 Clusterin（CLU）。此外，我们发现 NONHSAT105177 的转运是由外泌体介导的。我们目前和先前研究的综合结果表明，NONHSAT105177 介导了蜂毒素诱导的 PDAC 细胞生长和转移抑制，这表明它是开发新策略的潜在靶点。
