高通量测序鉴定乳腺癌分泌的外泌体 LncRNAs 引发肺前转移龛形成。
High throughput sequencing identifies breast cancer-secreted exosomal LncRNAs initiating pulmonary pre-metastatic niche formation.
机构信息
The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, PR China; Department of Clinical Laboratory, the Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, PR China; Department of General Surgery, the Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, PR China.
Department of Clinical Laboratory, the Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, PR China.
出版信息
Gene. 2019 Aug 20;710:258-264. doi: 10.1016/j.gene.2019.06.004. Epub 2019 Jun 7.
OBJECTIVE
Increasing evidence indicated that cancer-secreted exosomes played an important role in tumor metastasis. However, the function of exosomes in breast cancer pulmonary metastasis remains unknown. The aim of the study was to investigate the role of exosome-derived from breast cancer-secreted long non-coding RNAs (LncRNAs) on pre-metastatic niche formation in pulmonary metastasis.
METHODS
Exosomes-derived from breast cancer were separated by ultracentrifugation. The high-throughput sequencing, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used to detect and evaluate the differential expression of LncRNAs in lung fibroblasts with exosomes treated. And quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify candidate LncRNAs expression.
RESULTS
We found that exosomes-derived from breast cancer induced lung fibroblasts proliferation and migration. In addition, a large number of LncRNAs expression abnormalities were involved in the breast cancer lung metastasis microenvironment.
CONCLUSION
Our findings suggested that exosomal LncRNAs facilitated tumor pre-metastatic niche formation and represented a novel mechanistic insight into the molecular mechanism of cancer metastasis microenvironment.
目的
越来越多的证据表明，癌症来源的外泌体在肿瘤转移中发挥着重要作用。然而，外泌体在乳腺癌肺转移中的作用尚不清楚。本研究旨在探讨乳腺癌分泌的长链非编码 RNA（LncRNA）来源的外泌体在肺转移前微环境形成中的作用。
方法
通过超速离心分离乳腺癌来源的外泌体。采用高通量测序、基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析，检测并评估外泌体处理的肺成纤维细胞中 LncRNA 的差异表达。采用实时定量聚合酶链反应（qRT-PCR）验证候选 LncRNA 的表达。
结果
我们发现乳腺癌来源的外泌体可诱导肺成纤维细胞增殖和迁移。此外，大量 LncRNA 的表达异常参与了乳腺癌肺转移微环境。
结论
我们的研究结果表明，外泌体 LncRNA 促进了肿瘤转移前微环境的形成，并为癌症转移微环境的分子机制提供了新的认识。
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