Exosome内非编码RNAs检测在胃癌诊疗中的应用及机制

Exosome内非编码RNA（miRNA和lncRNA）作为一种新的非创伤性分子标志物在肿瘤诊疗中的作用备受关注。我们检测到胃癌微环境间质干细胞分泌的exosome内miR-423-5p及7SKRNA等非编码RNAs在胃癌患者血清exosome内显著增高，并发现miR-423-5p可促进胃癌细胞转移及上皮细胞间质化，但其在胃癌诊疗中的应用价值还有待评估。本研究拟采用qRT-PCR方法检测胃癌患者血清exosome内miR-423-5p及7SKRNA等非编码RNAs的表达水平，建立分子实验室诊断新技术，与传统方法比较并进行方法学评价，评估其单独和联合检测在胃癌诊疗中的应用价值；采用基因转染及CRISPR/Cas9基因敲除技术，结合细胞和动物模型解析exosome内miR-423-5p及7SKRNA在胃癌转移中的作用及机制。将为胃癌诊疗提供新技术和分子标志，为胃癌诊治提供新靶标，具有重要意义。

Exosomal non-coding RNA (miRNA and lncRNA), as emerging non-invasive markers for the diagnosis and therapy of cancers, have attracted increasing attention. Previously, we found that the levels of serum exosomal non-coding RNA (miR-423-5p and 7SKRNA) derived from GC-MSC exosome were significantly increased in patients with gastric cancer compared to that in healthy control. Our results also showed that miR-423-5p could promote EMT and metastasis of gastric cancer cells. However，the clinical significance of exosomal non-coding RNAs in diagnosis and treatment of gastric cancer remains to be evaluated. Therefore, in this proposal we aim to establish a new method for detecting exosomal non-coding RNAs , then we will assess the value of separate and combined detection of exosomal non-coding RNAs in diagnosis of gastric cancer compared with traditional methods. The roles and mechanisms of exosomal non-coding RNA will be explored by using cell and animal models as well as CRISPR/Cas9 technique. Our study will provide new methods and novel biomarkers for gastric cancer diagnosis, reveal the roles and mechanisms of these exosomal non-coding RNAs in cancer metastasis, and provide new therapeutic targets.