Chen Yingji, Ji Ying, Liu Suo, Liu Yicai, Feng Wei, Jin Longyu
Department of Cardiothoracic Surgery, Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha City, Hunan, China.
Department of Thoracic Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
Cancer Cell Int. 2022 Jan 11;22(1):19. doi: 10.1186/s12935-022-02448-7.
The roles of Polypyrimidine tract-binding protein 3 (PTBP3) in regulating lung squamous cell carcinoma (LUSC) cells progression is unclear. The aim of this study was to investigate the role of PTBP3 in LUSC.
Expression and survival analysis of PTBP3 was firstly investigated using TCGA datasets. Quantitative reverse transcription PCR and Western blot were performed to detect PTBP3 expression in clinical samples. Moreover, cell counting kit 8 (CCK-8) assays, colony formation assays and in vivo tumor formation assays were used to examine the effects of PTBP3 on LUSC cell proliferation. RNA-sequence and analysis explores pathways regulated by PTBP3.Flow cytology was used analyzed cell cycle. Cell cycle-related markers were analyzed by Western blot.
PTBP3 was found to be overexpressed in LUSC tissues compared with normal tissues. High PTBP3 expression was significantly correlated with poor prognosis. In vitro and vivo experiments demonstrated that PTBP3 knockdown caused a significant decrease in the proliferation rate of cells. Bioinformatics analysis showed that PTBP3 involved in cell cycle pathway regulation in LUSC. Furthermore, PTBP3 knockdown arrested cell cycle progression at S phase via decreasing CDK2/Cyclin A2 complex. In addition, downregulation of PTBP3 significantly decreased the expression of CDC25A.
Our results suggest that PTBP3 regulated LUSC cell proliferation via cell cycle and might be a potential target for molecular therapy of LUSC.
多嘧啶束结合蛋白3（PTBP3）在调节肺鳞状细胞癌（LUSC）细胞进展中的作用尚不清楚。本研究旨在探讨PTBP3在LUSC中的作用。
首先使用TCGA数据集对PTBP3进行表达和生存分析。采用定量逆转录PCR和蛋白质免疫印迹法检测临床样本中PTBP3的表达。此外，使用细胞计数试剂盒8（CCK-8）检测、集落形成检测和体内肿瘤形成检测来研究PTBP3对LUSC细胞增殖的影响。通过RNA测序和分析探索PTBP3调控的信号通路。采用流式细胞术分析细胞周期。通过蛋白质免疫印迹法分析细胞周期相关标志物。
与正常组织相比，PTBP3在LUSC组织中过表达。PTBP3高表达与预后不良显著相关。体外和体内实验表明，PTBP3基因敲低导致细胞增殖率显著降低。生物信息学分析表明，PTBP3参与LUSC细胞周期通路的调控。此外，PTBP3基因敲低通过降低CDK2/Cyclin A2复合物使细胞周期进程停滞在S期。此外，PTBP3的下调显著降低了CDC25A的表达。
我们的结果表明，PTBP3通过细胞周期调节LUSC细胞增殖，可能是LUSC分子治疗的潜在靶点。
