Wang Qiu-Li, Liu Ling
Department of Nephrology, Jining NO.1 People's Hospital, Jining, 272100, Shandong, China.
Department of Nephrology, Jining NO.1 People's Hospital , No.6 Jiankang Road, Jining, 272100, Shandong, China.
Open Med (Wars). 2019 Aug 14;14:586-592. doi: 10.1515/med-2019-0066. eCollection 2019.
We aimed to determine the function of pyrroline-5-carboxylate reductase 1 (PYCR1) on progression of papillary renal cell carcinoma (PRCC) and related mechanism.
The TCGA database provided us expression profiles of PYCR1 and overall survival rates. Small interfering RNA (siRNA) was used to knockdown PYCR1; quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were conducted to identify the expression levels of mRNA and protein. The cell counting kit-8 (CCK-8) and colony formation assays were used to explore cell viability in Ketr-3 cells. The migration and invasion of Ketr-3 cells were investigated by transwell assays.
We found that PYCR1 was over-expressed in PRCC tissues and cells, causing poor outcomes. Moreover, reduction of PYCR1 played a negative role on cell proliferation, migration and invasion in tumor cells. The important Akt/mTOR pathway proteins, phosphorylated Akt (p-Akt) and phosphorylated mTOR (p-mTOR), also showed lower levels compared with control groups.
These findings showed that disordered expression of PYCR1 could modulate PRCC progression through the Akt/mTOR pathway, implying a theoretical basis for PYCR1 as a potential therapeutic target in future clinical PRCC treatment.
我们旨在确定吡咯啉 - 5 - 羧酸还原酶1(PYCR1)在乳头状肾细胞癌(PRCC)进展中的作用及相关机制。
TCGA数据库为我们提供了PYCR1的表达谱和总生存率。使用小干扰RNA(siRNA)敲低PYCR1;进行定量实时聚合酶链反应(qRT-PCR)和蛋白质印迹法以鉴定mRNA和蛋白质的表达水平。使用细胞计数试剂盒 - 8(CCK - 8)和集落形成试验来探究Ketr - 3细胞的细胞活力。通过Transwell试验研究Ketr - 3细胞的迁移和侵袭能力。
我们发现PYCR1在PRCC组织和细胞中过表达,导致预后不良。此外,PYCR1的降低对肿瘤细胞的增殖、迁移和侵袭起负面作用。与对照组相比,重要的Akt/mTOR通路蛋白,磷酸化Akt(p-Akt)和磷酸化mTOR(p-mTOR)也显示出较低水平。
这些发现表明,PYCR1的异常表达可通过Akt/mTOR通路调节PRCC的进展,这为PYCR1作为未来临床PRCC治疗的潜在治疗靶点提供了理论依据。