LncRNA LIPH-4调控IGF2BP2表达促进食管鳞癌生长转移的作用及机制研究

We previously used a long non-coding RNA (lncRNA) microassay to compare the expression difference of lncRNAs in the oesophageal squamous cell carcinoma (ESCC) tissues and normal tissues adjacent to tumors, and found that the expression of a novel lncRNA LIPH-4 was up-regulated in the ESCC tissues. Knockdown of LIPH-4 in ESCC cells inhibited the malignant characteristics of ESCC cells; LIPH-4 might function as a competing endogenous RNA (ceRNA) and upregulted IGF2BP2 expression via miR-126b. To further investigate the role and molecular mechanism of LIPH-4 in ESCC, we will establish ESCC cell lines and human immortalization esophageal epithelial cell line with LIPH-4 expression changed, and determine the effects of LIPH-4 on the proliferation and metastasis of ESCC cells; investigate whether lLIPH-4 regulates IGF2BP2 expression as a ceRNA binds to miR-216b; finally analyze the effect of LIPH-4 on the signaling pathways downstream of IGF2BP2. This study will define LIPH-4 as a novel lncRNA, and elucidate the role and molecular mechanism of LIPH-4 in the ESCC, which will provide a scientific basis for LIPH-4 as a novel diagnosis and therapy target of this disease.

我们前期采用芯片技术分析食管鳞癌与癌旁组织的差异表达长链非编码RNA（lncRNA），发现一个新的lncRNA LIPH-4在癌组织中高表达，敲低LIPH-4抑制食管鳞癌细胞的恶性生物学特征，LIPH-4可能作为竞争性内源RNA（ceRNA）通过miR-216b调控IGF2BP2表达。为进一步揭示LIPH-4在食管鳞癌中的作用及机制，项目拟建立LIPH-4表达改变的食管鳞癌细胞系及永生化的食管上皮细胞系，分析LIPH-4对细胞生长和转移的影响，明确LIPH-4在食管癌发生发展中的作用；分析LIPH-4是否作为ceRNA与miR-216b结合而调控IGF2BP2表达以及LIPH-4对IGF2BP2下游信号通路的影响，明确LIPH-4的作用机制。项目研究将鉴定一个全新的lncRNA，揭示LIPH-4在食管鳞癌中的促癌作用及其分子机制，为LIPH-4作为新型食管鳞癌标志物及治疗靶标提供科学依据。

我国是食管鳞癌高发国家，发病人数占全球90%以上。食管鳞癌患者的治疗效果欠佳，其5年生存率仅为15%左右。深入研究食管鳞癌发病的分子机制及其治疗靶标，开发新的食管鳞癌防治方法，对于提高食管癌疗效以及降低食管癌死亡率具有重要意义。长链非编码RNA（lncRNA）在食管鳞癌的发生发展中发挥重要作用。本项目研究发现lncRNA LIPH-4在食管鳞癌组织和细胞中高表达，lncRNA LIPH-4能增加食管鳞癌细胞的增殖和转移能力，促进食管鳞癌细胞在裸鼠体内的生长。lncRNA LIPH-4可能作为竞争性内源RNA结合miR-216b而调控IGF2BP2的表达，进而促进食管鳞癌的发生发展。本项目率先鉴定了一个新的食管鳞癌促癌基因lncRNA LIPH-4，为食管鳞癌的防治提供了新靶点。