正常组织微环境对维持组织稳态及抑制肿瘤发生至关重要，但机制未明。我们前期研究发现，正常组织成纤维细胞（NF）分泌的IL-24对维持组织微环境稳态、抑制肿瘤细胞增殖发挥重要作用。通过对比NF和癌症相关成纤维细胞（CAF）发现，NF高表达miR-205和IL-24，低表达miR-222，而CAF正相反，miR-205可调控IL-24表达，由此提出NF通过miR-205/IL-24/miR-222通路发挥维持微环境稳态及抑制肿瘤细胞增殖的科学假设。拟通过高通量技术、细胞共培养及上皮3维培养、IL-24/miR-205/miR-222基因过表达及敲低、“拯救”实验、细胞周期、增殖和凋亡实验、Rea-time PCR、western blot、免疫组化、NF/IL-24抑制裸鼠移植瘤实验、建立过表达和敲低IL-24的转基因小鼠，并利用4NQO诱导口腔癌，研究NF/IL-24的作用机制。

Normal tissue microenvironment is important for maintenance of tissue homeostasis and inhibition of tumor initiation, but the underlying mechanism remains largely unknown. Based on our preliminary data, we find that IL-24 secreted from normal tissue fibroblasts (NF) play a key role in maintaining tissue homeostasis and inhibiting tumor proliferation. Compared with cancer-associated fibroblasts (CAF), NF expresses high level of miR-205 and IL-24 and low level of miR-222, while CAF expresses reversely. MiR-205 can regulate IL-24 directly. Based on the above data, we propose the hypothesis that normal tissue fibroblasts maintain microenvironment homeostasis and inhibit the proliferation of oral cancer cells through miR-205/IL-24/miR-222 pathway. We are planning to test the hypothesis and underlying mechanisms by using high through-put technology, tumor cell-fibroblasts co-culture and 3D epithelial culture, overexpression and knock-down of IL-24/miR-205/miR-222, “rescue” experiments, cell cycle analysis, cell proliferation/apoptosis assays, rea-time PCR, western blot, immunostaining, tumor xenografts inhibition in nude mice by NF/IL-24, establishment of IL-24 transgenic and knockout mice, then using 4NQO to induce oral epithelial dysplasia and cancer, to study the underlying mechanisms involved.