Schwarzmueller Laura, Bril Oscar, Vermeulen Louis, Léveillé Nicolas
Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Oncode Institute, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Cancers (Basel). 2020 Dec 19;12(12):3843. doi: 10.3390/cancers12123843.
Maintenance of the intestinal epithelium is dependent on the control of stem cell (SC) proliferation and differentiation. The fine regulation of these cellular processes requires a complex dynamic interplay between several signaling pathways, including Wnt, Notch, Hippo, EGF, Ephrin, and BMP/TGF-β. During the initiation and progression of colorectal cancer (CRC), key events, such as oncogenic mutations, influence these signaling pathways, and tilt the homeostatic balance towards proliferation and dedifferentiation. Therapeutic strategies to specifically target these deregulated signaling pathways are of particular interest. However, systemic blocking or activation of these pathways poses major risks for normal stem cell function and tissue homeostasis. Interestingly, long non-coding RNAs (lncRNAs) have recently emerged as potent regulators of key cellular processes often deregulated in cancer. Because of their exceptional tissue and tumor specificity, these regulatory RNAs represent attractive targets for cancer therapy. Here, we discuss how lncRNAs participate in the maintenance of intestinal homeostasis and how they can contribute to the deregulation of each signaling pathway in CRC. Finally, we describe currently available molecular tools to develop lncRNA-targeted cancer therapies.
肠道上皮的维持依赖于干细胞（SC）增殖和分化的调控。这些细胞过程的精细调节需要几种信号通路之间复杂的动态相互作用，包括Wnt、Notch、Hippo、EGF、Ephrin和BMP/TGF-β。在结直肠癌（CRC）的发生和发展过程中，致癌突变等关键事件会影响这些信号通路，并使稳态平衡向增殖和去分化倾斜。专门针对这些失调信号通路的治疗策略备受关注。然而，对这些通路的系统性阻断或激活对正常干细胞功能和组织稳态构成重大风险。有趣的是，长链非编码RNA（lncRNA）最近已成为癌症中经常失调的关键细胞过程的有效调节因子。由于其特殊的组织和肿瘤特异性，这些调节性RNA是癌症治疗的有吸引力的靶点。在这里，我们讨论lncRNA如何参与肠道稳态的维持，以及它们如何导致CRC中每个信号通路的失调。最后，我们描述了目前用于开发针对lncRNA的癌症治疗的分子工具。
