Rab3A诱导非经典自噬在肺癌细胞转移中的机制研究

肺癌是发病率﹑致死率最高的恶性肿瘤,主要是由于其进展迅速所致，但其机制仍待阐明。前期对肺癌（有/无转移）的PDX组织进行转录组测序，鉴定出Rab3A在有转移的PDX组织中高表达。过表达Rab3A可促进肺癌细胞迁移，敲低反之。进一步研究发现Rab3A对肺癌细胞转移的调控可能与其诱导的非经典自噬有关。由此我们推测：Rab3A可以通过诱导非经典自噬调控肺癌细胞的转移。为验证这一假说，本项目拟通过体内外实验进一步确认Rab3A促进肺癌细胞转移功能，明确Rab3A诱导的非经典自噬促进肺癌转移的分子机制；鉴定出Rab3A诱导自噬所降解的底物“X”；根据Rab3A与其调控的底物“X”的表达情况，建立统计学模型来判定Rab3A及其降解底物“X”对肺癌患者的预后价值。本项目的完成，将首次阐明Rab3A诱导的非经典自噬在肺癌细胞转移中的分子机制及功能，为肺癌转移的预后判断提供新的思路。

lung cancer is the most frequent and fatal malignant tumor, mainly due to its rapid progression, but its mechanism remains to be elucidated. We performed transcriptome sequencing of lung cancer PDX (with and without metastasis) tissues earlier and identified Rab3A as highly expressed in metastatic PDX tissues. Overexpression of Rab3A promoted lung cancer cell migration which was inhibited when Rab3A was knocked down. We found that Rab3A regulated the metastasis of lung cancer cells was correlated with Rab3A-induced nonclassical autophagy. So we suspect that Rab3A regulated the metastasis of lung cancer cells by inducing nonclassical autophagy. To verify this hypothesis, this project intends to confirm further in vivo and in vitro that Rab3A promotes lung cancer migration function; clarify the molecular mechanism of non-classical autophagy induced by Rab3A which promoted the lung cancer metastasis; identify the substrate “X ” which degraded by Rab3A-induced autophagy; and establish a statistical model to predict the prognosis of lung cancer patients based on the expression of Rab3A and its regulated substrate“ X ”. After the project was finished, the molecular mechanism and function of Rab3A-induced nonclassical autophagy were firstly elucidated in lung cancer metastasis, it might provide a new idea for prognosis of lung cancer metastasis.