Luo Hai-Tao, Zheng Yuan-Yuan, Tang Jun, Shao Li-Juan, Mao Yi-Heng, Yang Wei, Yang Xiao-Fei, Li Yang, Tian Rui-Jun, Li Fu-Rong
Translational Medicine Collaborative Innovation Center, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China.
Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, Shenzhen, China.
NPJ Genom Med. 2021 Jun 14;6(1):48. doi: 10.1038/s41525-021-00217-5.
Lung adenocarcinoma is heterogeneous and hierarchically organized, with a subpopulation of stem-like cells (CSCs) that reside at the apex of the hierarchy, in which exosomes act as important mediators by transporting specific molecules among different cell populations. Although there have been numerous studies on tumor exosomes, the constituents and functional properties of CSC-derived exosomes are still poorly characterized. Here we present a detail transcriptome and proteome atlas of the exosomes released by human lung adenocarcinoma stem-like cells (LSLCs). The transcriptome analysis indicates the specific patterns of exosomal constituents, including the fragmentation of transcripts and the low-level presence of circular RNAs, and identifies multiple exosomal-enriched mRNAs and lncRNAs. Integrative analysis of transcriptome and proteome data reveals the diverse functions of exosomal-enriched RNAs and proteins, many of which are associated with tumorigenesis. Importantly, several LSLC markers we identified are highly expressed in LSLC-derived exosomes and associate with poor survival, which may serve as promising liquid biopsy biomarkers for lung adenocarcinoma diagnosis. Our study provides a resource for the future elucidation of the functions of tumor-derived exosomes and their regulatory mechanisms in mediating lung cancer development.
肺腺癌具有异质性且呈分层组织，存在一群位于层级顶端的干细胞样细胞（CSCs），其中外泌体通过在不同细胞群体间运输特定分子而充当重要介质。尽管对肿瘤外泌体已有众多研究，但CSC来源的外泌体的成分和功能特性仍未得到充分表征。在此，我们展示了人肺腺癌干细胞样细胞（LSLCs）释放的外泌体的详细转录组和蛋白质组图谱。转录组分析揭示了外泌体成分的特定模式，包括转录本的片段化和环状RNA的低水平存在，并鉴定出多个外泌体富集的mRNA和lncRNA。转录组和蛋白质组数据的综合分析揭示了外泌体富集的RNA和蛋白质的多种功能，其中许多与肿瘤发生相关。重要的是，我们鉴定出的几种LSLC标志物在LSLC来源的外泌体中高度表达且与不良生存相关，这可能作为有前景的液体活检生物标志物用于肺腺癌诊断。我们的研究为未来阐明肿瘤来源外泌体的功能及其在介导肺癌发展中的调控机制提供了资源。
