Department of Anatomy, School of Basic Medicine, Guizhou Medical University, Guiyang, China.
Department of Anatomy, School of Basic Medicine, Guizhou Nursing Vocational college, Guiyang, China.
J Cell Mol Med. 2023 Sep;27(17):2533-2546. doi: 10.1111/jcmm.17852. Epub 2023 Jul 24.
The pancreatic stellate cells (PSCs) play an important role in the development of pancreatic cancer (PC) through mechanisms that remain unclear. Exosomes secreted from PSCs act as mediators for communication in PC. This study aimed to explore the role of PSC-derived exosomal small RNAs derived from tRNAs (tDRs) in PC cells. Exosomes from PSCs were extracted and used to detect their effects on PC cell proliferation, migration and invasion. Exosomal tDRs profiling was performed to identify PSC-derived exosomal tDRs. ISH and qRT-PCR were used to examine the tRF-19-PNR8YPJZ levels and clinical value in clinical samples. The biological function of exosomal tRF-19-PNR8YPJZ was determined using the CCK-8, clone formation, wound healing and transwell assays, subcutaneous tumour formation and lung metastatic models. The relationship between the selected exosomal tRF-19-PNR8YPJZ and AXIN2 was determined by RNA sequencing, luciferase reporter assay. PSC-derived exosomes promoted the proliferation, migration, and invasion of PC cells. Novel and abundant tDRs are found to be differentially expressed in PANC-1 cells after treatment with PSC-derived exosomes, such as tRF-19-PNR8YPJZ. PC tissue samples showed markedly higher levels of tRF-19-PNR8YPJZ than normal controls. Patients with PC exhibiting high tRF-19-PNR8YPJZ expression had a highly lymph node invasion, metastasis, perineural invasion, advanced clinical stage and poor overall survival. Exosomal tRF-19-PNR8YPJZ from PSCs targeted AXIN2 in PC cells and decreased its expression, thus activating the Wnt pathway and promoting proliferation and metastasis. Exosomal tRF-19-PNR8YPJZ from PSCs promoted proliferation and metastasis in PC cells via AXIN2.
胰腺星状细胞（PSCs）通过尚不清楚的机制在胰腺癌（PC）的发展中发挥重要作用。PSCs 分泌的外泌体作为 PC 细胞通讯的介质。本研究旨在探索 PSC 衍生的小 RNA 来源的转移 RNA（tRNA）衍生的小 RNA（tDRs）在外泌体中的作用。提取 PSCs 的外泌体，并用于检测其对 PC 细胞增殖、迁移和侵袭的影响。进行外泌体 tDR 谱分析以鉴定 PSC 衍生的外泌体 tDRs。ISH 和 qRT-PCR 用于检测临床样本中的 tRF-19-PNR8YPJZ 水平和临床价值。使用 CCK-8、克隆形成、划痕愈合和 Transwell 测定、皮下肿瘤形成和肺转移模型来确定外泌体 tRF-19-PNR8YPJZ 的生物学功能。通过 RNA 测序、荧光素酶报告测定确定选定的外泌体 tRF-19-PNR8YPJZ 与 AXIN2 之间的关系。PSC 衍生的外泌体促进 PC 细胞的增殖、迁移和侵袭。在 PSC 衍生的外泌体处理后，发现 PANC-1 细胞中存在新型且丰富的 tDRs，如 tRF-19-PNR8YPJZ。PC 组织样本显示的 tRF-19-PNR8YPJZ 水平明显高于正常对照。显示高 tRF-19-PNR8YPJZ 表达的 PC 患者具有较高的淋巴结侵犯、转移、神经周围侵犯、晚期临床分期和较差的总体生存。来自 PSCs 的外泌体 tRF-19-PNR8YPJZ 靶向 PC 细胞中的 AXIN2 并降低其表达，从而激活 Wnt 通路并促进增殖和转移。来自 PSCs 的外泌体 tRF-19-PNR8YPJZ 通过 AXIN2 促进 PC 细胞的增殖和转移。
