原发性结直肠肿瘤干细胞中 miRNAs 的表达谱、分子功能和预后意义。
Expression profile, molecular functions, and prognostic significance of miRNAs in primary colorectal cancer stem cells.
机构信息
Institute of Digestive Surgery, Sichuan University, and Department of Gastrointestinal Surgery, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China.
Department of Gastrointestinal Surgery and Breast and Thyroid Surgery, Minimally Invasive Surgery, West China Fourth Hospital, Sichuan University, Chengdu, China.
出版信息
Aging (Albany NY). 2021 Apr 1;13(8):12067-12085. doi: 10.18632/aging.202914.
MicroRNAs (miRNAs) are known to drive the pathogenesis of colorectal cancer (CRC) via the regulation of cancer stem cells (CSCs). We studied the miRNA expression profile of primary CSCs isolated from patients with CRC (pCRCSCs). Compared to pCRCSC-derived differentiated cells, 98 differentially expressed miRNAs were identified in pCRCSCs. Target genes encoding pCRCSC-related miRNAs were identified using a combination of miRNA target databases and miRNA-mRNA regulatory networks from the same patient. The pCRCSC-related miRNA target genes were associated with pathways contributing to malignant phenotypes, including I-kappa B kinase/NF-kappa B signaling, signal transduction by p53 class mediator, Ras signaling, and cGMP-PKG signaling. The pCRCSC-related miRNA expression signature was independently associated with poor overall survival in both the training and validation cohorts. We have thus identified several pCRCSC-related miRNAs with oncogenic potential that could serve as prognostic biomarkers for CRC.
微 RNA（miRNA）被认为通过调节癌症干细胞（CSC）来驱动结直肠癌（CRC）的发病机制。我们研究了从 CRC 患者中分离出的原发性 CSC（pCRCSC）的 miRNA 表达谱。与 pCRCSC 衍生的分化细胞相比，在 pCRCSC 中鉴定出 98 个差异表达的 miRNA。使用 miRNA 靶标数据库和来自同一患者的 miRNA-mRNA 调控网络的组合，鉴定出编码 pCRCSC 相关 miRNA 的靶基因。pCRCSC 相关 miRNA 靶基因与促进恶性表型的途径相关，包括 I-κB 激酶/NF-κB 信号、p53 类介质的信号转导、Ras 信号和 cGMP-PKG 信号。pCRCSC 相关 miRNA 表达特征在训练和验证队列中均与总体生存不良独立相关。因此，我们鉴定出了一些具有致癌潜力的 pCRCSC 相关 miRNA，它们可以作为 CRC 的预后生物标志物。
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