长链非编码RNA HUESSC在食管鳞状细胞癌变过程中的功能及其调控机制研究

The dysregulation of long noncoding RNAs(lncRNAs) lead to the development and progression of tumor. Many studies have confirmed the overavtivity of glycolysis is a significant biochemical characteristics of the tumor cells. We found the expression of lncRNA CHUESC was increased of more than 10 times in tissues of esophageal squamous cell carcinoma by lncRNA array and qRT-PCR. CHUESC can significantly inhibited tumor cell proliferation by siRNA.Tracking the literature suggests that lncRNA study on the mechanism of regulation of proliferation in the process of esophageal carcinoma has not been reported. Recent studies confirmed that the LncRNA could competitively binding with miRNA,then accelerated the expression of miRNA-targeted-gene and executed related functions. We found HUESCC possibly could regulate miRNA-143, miR-125a-5p and its target genes HK2(hexose kinase 2), to promote the proliferation of esophageal squamous cell carcinoma cells after bioinformatic prediction and function enrichment analysis of target genes. We will futher verify whether this mechanism could promote the proliferation of tumor cells at the level of tissues, vivo and in vitro by affecting glucose metabolism and explore the regulatory mechanisms of HUESCC upstream. At last,we will detected HUESCC expression level in blood between normal subjects, esophagitis, esophageal precancerous lesions and patients with esophageal cancer, preliminary investigat its potential value as a clinical diagnostic indicators.

长链非编码RNA（lncRNA）的异常表达可导致肿瘤的发生发展。诸多研究证实异常活跃的糖酵解代谢是肿瘤细胞的显著生化特征。课题组经芯片和qRT-PCR在食管鳞癌中发现lncRNA CHUESC表达平均上调10倍以上，siRNA敲降CHUESC后可显著抑制肿瘤细胞增殖。追踪文献lncRNA在食管鳞癌中调控增殖的机制研究迄今未见报道。新近研究证实LncRNA可与miRNA竞争性结合，上调miRNA靶基因的表达并行使相关功能。生物信息学预测及靶基因功能富集分析发现HUESCC可能通过调控miRNA-143、miR-125a-5p及其靶基因己糖激酶2，促进食管鳞癌细胞的增殖。课题组将在组织、细胞和活体动物水平验证这一机制是否通过影响糖代谢促进肿瘤细胞的增殖，探索HUESCC上游调控机制，并比较正常人、食管炎、食管癌前病变和食管癌患者血液中HUESCC表达水平，初步探其作为临床诊断指标的潜在价值。

食管鳞癌（ESCC）是世界范围内最常见且致死率最高的恶性肿瘤之一。以往的研究证实LncRNA在ESCC发生发展中具有重要作用。长链非编码RNA HOTAIR在ESCC中具有重要的调控作用。我们主要在ESCC中研究了 HOTAIR直接靶向结合miR-125和 miR-143 从而影响己糖激酶2（HK2）的表达。我们的研究证实长链非编码RNA HOTAIR通过作用miR-125-miR-143-HK2轴，调控糖酵解过程，影响肿瘤细胞的增殖。内源性竞争性RNA作用模式，即HOTAIR/miR-125 and miR143/HK2作用轴可能会成为ESCC诊断及治疗的重要靶标。