State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China.
Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
J Cell Physiol. 2019 Dec;234(12):22703-22718. doi: 10.1002/jcp.28836. Epub 2019 May 23.
Colon cancer stem cells (CCSCs) stand for a critical subpopulation of colon cancer cells that possess self-renewal and multilineage differentiation potentials and drive tumorigenicity. Due to their impact on treatment tolerance, CCSCs have been a hot research topic in the past few years. We have previously reported that miR-139-5p is a vital tumor repressive noncoding RNA whose level decreases in the clinical colon cancer samples with the increase of tumor malignancy. This research discovered that miR-139-5p targets the Wnt/β-catenin/TCF7L2 downstream effector E2-2 in CCSCs. E2-2 is a pivot molecule in the negative feedback loop of miR-139-5p/Wnt/β-catenin/TCF7L2. Its small interfering RNA reverses the stemness maintenance and epithelial-mesenchymal transition of colon cancer CSCs. This study provides a theoretical foundation for the clinical diagnosis and medical treatment of recurrent or metastatic colon cancer with miR-139-5p and its target E2-2.
结直肠肿瘤干细胞（CCSCs）代表了结直肠癌细胞中的一个关键亚群，其具有自我更新和多谱系分化潜能，并驱动肿瘤发生。由于其对治疗耐受性的影响，CCSCs 是过去几年的热门研究课题。我们之前曾报道过，miR-139-5p 是一种重要的肿瘤抑制性非编码 RNA，其水平随着肿瘤恶性程度的增加而在临床结直肠癌样本中降低。本研究发现，miR-139-5p 靶向 CCSCs 中的 Wnt/β-catenin/TCF7L2 下游效应物 E2-2。E2-2 是 miR-139-5p/Wnt/β-catenin/TCF7L2 负反馈环中的关键分子。其小干扰 RNA 逆转了结直肠肿瘤 CSCs 的干性维持和上皮-间充质转化。这项研究为 miR-139-5p 及其靶标 E2-2 用于复发性或转移性结直肠癌的临床诊断和治疗提供了理论基础。
