LncRNA EPIC1调控非小细胞肺癌血管生成介导顺铂耐药机制的研究

顺铂耐药是影响非小细胞肺癌（NSCLC）中晚期治疗和预后的关键。肿瘤血管生成可促进肿瘤耐药。我们前期基于GEPIA数据库分析和实验验证发现lncRNA EPIC1在NSCLC组织、细胞中表达升高并与血管新生正相关，且过表达lnc-EPIC1促进肿瘤细胞分泌Ang2增加。研究表明，Ang2可参与肿瘤耐药；结合catRAPID数据库预测lnc-EPIC1能与PTBP1蛋白直接结合，PTBP1能与Ang2结合。我们推测，lnc-EPIC1作为一个架构RNA与PTBP1蛋白结合，招募PTBP1与Ang2 mRNA结合，增强Ang2 mRNA的稳定性，促进Ang2表达，调控NSCLC血管生成，并激活ERK-MSK通路，介导NSCLC顺铂耐药。本课题拟从分子、细胞、动物、临床等多个层面，探讨lnc-EPIC1调控NSCLC血管生成介导顺铂耐药的机制。为干预甚至逆转NSCLC顺铂耐药提供新靶点。

Cisplatin resistance is a key factor affecting the treatment and prognosis of advanced non-small cell lung cancer (NSCLC). Tumor angiogenesis promotes drug resistance. Based on the GEPIA database analysis and experimental verification, we previously found that the expression of lncRNA EPIC1 was increased in NSCLC tissues and cells and positively correlated with angiogenesis, and the overexpression of lnc-EPIC1 promoted the increase of Ang2 secretion in tumor cells. Studies have shown that Ang2 may be involved in tumor drug resistance. Combined with catRAPID database, it is predicted that lnc-EPIC1 can directly bind to PTBP1 protein and PTBP1 can bind to Ang2 protein. We speculated that lnc-EPIC1 , as an architectural RNA, binds to PTBP1 protein, recruits PTBP1 to bind to Ang2 mRNA, enhances the stability of Ang2 mRNA, promotes Ang2 expression, regulates angiogenesis of NSCLC, and activates the ERK-MSK pathway to mediate cisplatin resistance of NSCLC. This study aims to explore the mechanism of lnc-EPIC1 regulating NSCLC angiogenesis mediated cisplatin resistance from multiple levels including molecular, cellular, animal and clinical. It provides a new target for intervention or even reversal of cisplatin resistance in NSCLC.