Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Science, Nanjing Normal University, Nanjing 210023, China.
Department of Bioinformatics, Smart Health Big Data Analysis and Location Services Engineering Lab of Jiangsu Province, School of Geographic and Biologic Information, Nanjing University of Posts and Telecommunications, Nanjing 210023, China.
Genes (Basel). 2021 Oct 21;12(11):1659. doi: 10.3390/genes12111659.
Intrahepatic cholangiocarcinoma (ICC) is a common type of human cancer with a poor prognosis, and investigating the potential molecular mechanisms that can contribute to gene diagnosis and therapy. Herein, based on the recently concerned vertebrate-specific Cyr61/CTGF/NOV (CCN) gene family because of its important roles in diverse diseases, we obtained NOV/CCN3 to query for its potential roles in tumorigenesis via bioinformatics analysis. Experimental validations confirmed that both NOV mRNA and protein are up-regulated in two ICC cell lines, suggesting that it may promote cell migration and invasion by promoting EMT. To elucidate the detailed regulatory mechanism, miR-92a-3p is screened and identified as a negative regulatory small RNA targeting NOV, and further experimental validation demonstrates that miR-92a-3p contributes to NOV-mediated migration and invasion of ICC via the Notch signaling pathway. Our study reveals that NOV may be a potential target for diagnosing and treating ICC, which will provide experimental data and molecular theoretical foundation for cancer treatment, particularly for future precision medicine.
肝内胆管癌（ICC）是一种常见的人类癌症，预后不良，研究可能有助于基因诊断和治疗的潜在分子机制。在此，基于最近受到关注的脊椎动物特异性 Cyr61/CTGF/NOV（CCN）基因家族，因为其在多种疾病中的重要作用，我们通过生物信息学分析获得 NOV/CCN3 来查询其在肿瘤发生中的潜在作用。实验验证证实，两种 ICC 细胞系中 NOV mRNA 和蛋白均上调，表明 NOV 可能通过促进 EMT 促进细胞迁移和侵袭。为了阐明详细的调控机制，筛选并鉴定出 miR-92a-3p 是 NOV 的负调控小 RNA，进一步的实验验证表明，miR-92a-3p 通过 Notch 信号通路促进 NOV 介导的 ICC 迁移和侵袭。我们的研究表明，NOV 可能是 ICC 诊断和治疗的潜在靶点，这将为癌症治疗提供实验数据和分子理论基础，特别是为未来的精准医学。
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