Department of General Surgery, Huashan Hospital, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Carcinogenesis. 2023 Dec 2;44(8-9):671-681. doi: 10.1093/carcin/bgad063.
Extracellular vesicles (EVs) are bilayered membrane vesicles produced by living cells and secreted into the extracellular matrix. Bile is a special body fluid that is secreted by the liver cells, and extracellular vesicles long RNAs (exLRs) have not been explored in bile. In this study, exLR sequencing (exLR-seq) was performed on 19 bile samples from patients with malignant cancer or patients with biliary stones. A total of 8649 mRNAs, 13 823 circRNAs and 1105 lncRNAs were detected. The KEGG pathway analysis revealed that differentially expressed exLRs were enriched in mTOR and AMPK signaling pathway. We identified five mRNAs (EID2, LLPH, ATP6V0A2, RRP9 and MTRNR2L10), three lncRNAs (AC015922.2, AL135905.1 and LINC00921) and six circRNAs (circASH1L, circATP9A, circCLIP1, circRNF138, circTIMMDC1 and circANKRD12) were enriched in bile EV samples with cancer, and these exLRs may be potential markers used to distinguish malignant cancers from benign biliary diseases. Moreover, the tissue/cellular source components of EVs were analyzed using the EV-origin algorithm. The absolute abundance of CD4_naive and Th1 cell source in bile EVs from cancer patients were significantly increased. In summary, our study presented abundant exLRs in human bile EVs and provides some basis for the selection of tumor diagnostic markers.
细胞外囊泡 (EVs) 是由活细胞产生并分泌到细胞外基质中的双层膜囊泡。胆汁是一种特殊的体液，由肝细胞分泌，而细胞外囊泡长 RNA（exLRs）在胆汁中尚未被探索。在这项研究中，对 19 份来自恶性肿瘤患者或胆石症患者的胆汁样本进行了 exLR 测序（exLR-seq）。共检测到 8649 个 mRNAs、13823 个 circRNAs 和 1105 个 lncRNAs。KEGG 通路分析显示，差异表达的 exLRs 富集在 mTOR 和 AMPK 信号通路中。我们鉴定了五个 mRNAs（EID2、LLPH、ATP6V0A2、RRP9 和 MTRNR2L10）、三个 lncRNAs（AC015922.2、AL135905.1 和 LINC00921）和六个 circRNAs（circASH1L、circATP9A、circCLIP1、circRNF138、circTIMMDC1 和 circANKRD12）在富含癌症的胆汁 EV 样本中富集，这些 exLRs 可能是用于区分恶性肿瘤和良性胆道疾病的潜在标志物。此外，使用 EV 起源算法分析了 EV 的组织/细胞来源成分。癌症患者胆汁 EV 中 CD4_naive 和 Th1 细胞来源的绝对丰度显著增加。总之，我们的研究在人类胆汁 EV 中呈现了丰富的 exLRs，为肿瘤诊断标志物的选择提供了一些依据。
