美国哈佛医学院David T. Ting和美国丹娜-法伯癌症研究所Martin J. Aryee团队共同合作，近期取得重要工作进展。他们报道了人胰腺癌中RNA重复序列对细胞可塑性有破坏作用。相关研究成果2024年10月8日在线发表于《细胞》杂志上。
据介绍，胰腺导管腺癌（PDAC）中重复RNA的异常表达模拟了病毒样反应，对肿瘤细胞状态和周围微环境的反应有影响。
为了更好的了解重复RNA在人类PDAC中的关系，研究人员在46个原发性肿瘤中进行了单细胞分辨率的空间分子成像，揭示了高重复RNA表达与PDAC细胞上皮状态改变和癌症相关成纤维细胞（CAF）肌成纤维细胞表型的相关性。
这种细胞特性的丧失是通过给药细胞外囊泡（EV）和PDAC和CAF细胞培养模型的单个重复RNA观察到的，这些重复RNA指向了这些病毒样元件的细胞间相互通信。PDAC和CAF反应的差异是由通过干扰素调节因子3（IRF3）的不同先天免疫信号驱动的。对重复RNA的细胞环境特异性病毒样反应，提供了一种调节PDAC微环境中不同细胞类型细胞可塑性的机制。
附：英文原文
Title: Disruption of cellular plasticity by repeat RNAs in human pancreatic cancer
Author: Eunae You, Patrick Danaher, Chenyue Lu, Siyu Sun, Luli Zou, Ildiko E. Phillips, Alexandra S. Rojas, Natalie I. Ho, Yuhui Song, Michael J. Raabe, Katherine H. Xu, Peter M. Richieri, Hao Li, Natalie Aston, Rebecca L. Porter, Bidish K. Patel, Linda T. Nieman, Nathan Schurman, Briana M. Hudson, Khrystyna North, Sarah E. Church, Vikram Deshpande, Andrew S. Liss, Tae K. Kim, Yi Cui, Youngmi Kim, Benjamin D. Greenbaum, Martin J. Aryee, David T. Ting
Issue&Volume: 2024-10-08
Abstract: Aberrant expression of repeat RNAs in pancreatic ductal adenocarcinoma (PDAC) mimics viral-like responses with implications on tumor cell state and the response of the surrounding microenvironment. To better understand the relationship of repeat RNAs in human PDAC, we performed spatial molecular imaging at single-cell resolution in 46 primary tumors, revealing correlations of high repeat RNA expression with alterations in epithelial state in PDAC cells and myofibroblast phenotype in cancer-associated fibroblasts (CAFs). This loss of cellular identity is observed with dosing of extracellular vesicles (EVs) and individual repeat RNAs of PDAC and CAF cell culture models pointing to cell-cell intercommunication of these viral-like elements. Differences in PDAC and CAF responses are driven by distinct innate immune signaling through interferon regulatory factor 3 (IRF3). The cell-context-specific viral-like responses to repeat RNAs provide a mechanism for modulation of cellular plasticity in diverse cell types in the PDAC microenvironment.
DOI: 10.1016/j.cell.2024.09.024
Source: https://www.cell.com/cell/abstract/S0092-8674(24)01072-9