中文摘要
鹿茸角是唯一具周期性表形态再生能力的哺乳动物器官。随着快速生长期鹿茸角“肿瘤样”生长,顶端增生区茸性上皮保持着高增殖无凋亡状态,却无癌变发生。这提示茸皮再生高度可控并受到精细调控,具有稳态特性,但其机制不清。我们近期发现了一个马鹿(Cervus elaphus)茸皮特异性表达的新microRNA PC-5p-1090。预研实验显示,离体条件下PC-5p-1090有抑制肿瘤/癌症来源细胞系增殖的功能;且具miRNA行使功能时必需的结构特性,即直接结合靶基因mRNA上seed序列的互补序列。由此我们提出假说:PC-5p-1090具抑癌基因功能,可抑制茸皮细胞增殖,并参与调控茸皮生长发育。本项目拟通过实验获取可靠证据。PC-5p-1090将为我们深入理解再生鹿茸角器官/组织中细胞增殖负调控,以及整个内稳态保持的新机制提供一条重要途径,也为治疗肿瘤/癌症的潜在新药前体与靶标研究提供充分科学依据。
英文摘要
Deer antlers are the only mammalian appendages capable of periodical epimorphic regeneration. During the rapid growth stage, along with antler ‘tumor-like’ overgrowth from the top growth zones, antler velvet covered outside shows high proliferation and no apoptosis; however it is very resistant to tumor formation actually. This hints that velvet regeneration is a highly-controlled and well-coordinated developmental process showing homeostasis status. The mechanisms remained unclear. Previously, we isolated a novel velvety-specific-expressed microRNA, named of PC-5p-1090, from red deer antler. Our recent studies showed that PC-5p-1090 was capable of inhibiting tumor/cancer-derived cell proliferation in vitro, and able to bind directly to the seed-sequence complimentary site located in target gene mRNA, a necessary structural character for microRNA fulfilling functions. Thus, we proposed a new hypothesis that, functioned as a tumor suppressor role, PC-5p-1090 could inhibit velvet epithelia proliferation, and further regulate velvet growth and development. We will develop experiments to find reliable evidence. PC-5p-1090 would open an important way for deep understanding novel negative regulation and homeostasis maintaining mechanisms in growing antler, further this project will provide sufficient scientific evidence for developing novel nucleic acid medicine precursor and mining new medicine targets of human tumor/cancer therapy.
