文献类型：期刊文献

英文题名：PTBP3 contributes to the metastasis of gastric cancer by mediating CAV1 alternative splicing

作者：Liang, Xin[1,2];Chen, Weixia[3];Shi, Haiyang[1,2];Gu, Xiangyu[1,2];Li, Yueqi[1,2];Qi, Yingxue[1,2];Xu, Ke[4,5];Zhao, Aiguang[3];Liu, Jianwen[1,2]

机构：[1]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai, Peoples R China;[3]Shanghai Univ Tradit Chinese Med, Longhua Hosp, Dept Oncol, 725 South Wanping Rd, Shanghai 200032, Peoples R China;[4]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Cent Lab Gen Surg, Shanghai 200062, Peoples R China;[5]Shanghai Univ Tradit Chinese Med, Intervent Canc Inst Chinese Integrat Med, Shanghai 200062, Peoples R China

年份：2018

卷号：9

外文期刊名：CELL DEATH & DISEASE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000433089800012)】；

基金：This work was supported by the National Natural Science Foundation of China [nos. 81373861 and 81502540], Shanghai Science and Technology Committee [no. 17430741600], the scientific research of National TCM Clinical Research Base Construction [no. JDZX2015068], 3-year Action Plan for the Development of Traditional Chinese Medicine in Shanghai [no. ZY3-CCCX-3-2003], and the scientific research budgeted project of Shanghai University of TCM [no. 2015YSN51].

语种：英文

摘要：Polypyrimidine tract-binding protein 3 (PTBP3) is an essential RNA-binding protein with roles in RNA splicing, 3' end processing and translation. Although increasing evidence implicates PTBP3 in several cancers, its role in gastric cancer metastasis remains poorly explored. In this study, we found that PTBP3 was upregulated in the gastric cancer tissues of patients with lymph node metastasis. Patients with high PTBP3 expression levels had significantly shorter survival than those with low PTBP3 expression. Overexpression/knockdown of PTBP3 expression had no effect on proliferation, whereas it regulated migration and invasion in vitro. In addition, when a mouse xenotransplant model of MKN45 was established, knockdown of PTBP3 in MKN45 cells caused the formation of tumours that were smaller in size than their counterparts, with suppression of tumour lymphangiogenesis and metastasis to regional lymph nodes. Furthermore, we identified caveolin 1 (CAV1) as a downstream target of PTBP3. RNA immunoprecipitation (RIP) assays and dual-luciferase reporter gene assays indicated that PTBP3 interacted with the CU-rich region of the CAV1 gene to downregulate CAV1 alpha expression. Knockdown of CAV1 alpha abrogated the reduction of FAK and Src induced by PTBP3 knockdown. In summary, our findings provide experimental evidence that PTBP3 may function as a metastatic gene in gastric cancer by regulating CAV1 through alternative splicing.