Lu Xingre, Chen Fengyu, Yuan Diao, He Xiang, Liu Xiaowen, Zi Yunju, Lu Yu
Department of Clinical Laboratory, The People's Hospital of Wenshan Prefecture in Yunnan Province No. 228, Kaihua Middle Road Wenshan Yunnan 663000 China
RSC Adv. 2019 Nov 19;9(64):37642-37651. doi: 10.1039/c9ra07823a. eCollection 2019 Nov 13.
Bladder cancer (BC) is a lethal cancer that threatens the health of millions of people. Chemotherapy drug resistance, for example, cisplatin (DDP) resistance, is a huge limitation for BC therapy. PTEN pseudogene-1 (PTENP1) has been identified as a significant biomarker of multiple cancers. Therefore, it is essential to illuminate the molecular mechanism of PTENP1 in BC cell DDP resistance and progression. Serum exosomes were isolated using an ExoQuick precipitation kit. Serum exosomes were round-shaped vesicles of 100 ± 60 nm in size. The expression of PTENP1 was down-regulated in serum exosomes isolated from cisplatin non-responsive patients compared with responsive patients. ROC curves certified the diagnostic value of PTENP1. Apparently, PTENP1 transfection inhibited DDP-resistant BC cell proliferation, migration, cisplatin resistance and facilitated apoptosis. Next, we discovered that PTENP1 was a sponge of miR-103a, while PDCD4 was a target of miR-103a. More importantly, PTENP1 regulated DDP-resistant cell viability, migration, apoptosis and cisplatin resistance by interacting with the miR-103a/PDCD4 axis. In addition, PTENP1 hindered tumor growth of cisplatin-resistant mice. Exosome-derived PTENP1 suppressed the DDP resistance of BC by inhibiting cell proliferation, migration and promoting apoptosis through regulating the miR-103a/PDCD4 axis, representing a targeted therapy for DDP-resistant BC patients.
膀胱癌（BC）是一种威胁数百万人健康的致命癌症。化疗耐药性，例如顺铂（DDP）耐药性，是BC治疗的一个巨大限制。PTEN假基因-1（PTENP1）已被确定为多种癌症的重要生物标志物。因此，阐明PTENP1在BC细胞DDP耐药性和进展中的分子机制至关重要。使用ExoQuick沉淀试剂盒分离血清外泌体。血清外泌体是大小为100±60nm的圆形囊泡。与反应性患者相比，从顺铂无反应患者分离的血清外泌体中PTENP1的表达下调。ROC曲线证实了PTENP1的诊断价值。显然，PTENP1转染抑制了DDP耐药BC细胞的增殖、迁移、顺铂耐药性并促进了细胞凋亡。接下来，我们发现PTENP1是miR-103a的海绵，而PDCD4是miR-103a的靶标。更重要的是，PTENP1通过与miR-103a/PDCD4轴相互作用来调节DDP耐药细胞的活力、迁移、凋亡和顺铂耐药性。此外，PTENP1阻碍了顺铂耐药小鼠的肿瘤生长。外泌体来源的PTENP1通过调节miR-103a/PDCD4轴抑制细胞增殖、迁移并促进凋亡，从而抑制BC的DDP耐药性，这代表了一种针对DDP耐药BC患者的靶向治疗方法。
