Gu Biao, Yang Maoyuan, Shi Liang, Yuan Guangda, Xie Hongya, Ni Bin
Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University 899 Pinghai Road, Suzhou 215006, Jiangsu, China.
Department of Thoracic Surgery, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University 1 Huanghe West Road, Huai'an 223300, Jiangsu, China.
Am J Transl Res. 2023 Jul 15;15(7):4887-4901. eCollection 2023.
This study aimed to explore the specific mechanism of action of Progranulin (PGRN) in non-small cell lung cancer (NSCLC) and its interaction with lncRNA H19.
Normal and cancerous lung tissues were collected from patients with NSCLC and healthy volunteers. We assessed the expression of PGRN in both groups using immunohistochemistry, quantitative-reverse transcription-polymerase chain reaction (qRT-PCR), and western blotting (WB).
Compared to the controls, PGRN expression was noticeably higher in tumor tissues. The high expression of PGRN in patients with NSCLC was inversely correlated to the prognosis and strongly associated with the biological features and clinicopathologic data. High PGRN expression significantly improved the ability of NSCLC cells to proliferate and migrate and was positively correlated with tumor formation, based on in vitro and in vivo cellular tests. Expression of lncRNA H19 was also found to be elevated in NSCLC tissue and cells. The expression of H19 was correlated with tumor growth in vivo and in vitro, and H19 regulated PGRN by mediating the expression of miR-29b-3p.
H19 and PGRN can serve as biomarkers and therapeutic targets in NSCLC.
本研究旨在探讨颗粒蛋白前体(PGRN)在非小细胞肺癌(NSCLC)中的具体作用机制及其与长链非编码RNA H19的相互作用。
收集NSCLC患者和健康志愿者的正常肺组织及癌组织。我们采用免疫组织化学、定量逆转录聚合酶链反应(qRT-PCR)和蛋白质免疫印迹法(WB)评估两组中PGRN的表达。
与对照组相比,肿瘤组织中PGRN表达明显更高。NSCLC患者中PGRN的高表达与预后呈负相关,且与生物学特征及临床病理数据密切相关。基于体外和体内细胞试验,PGRN高表达显著提高了NSCLC细胞的增殖和迁移能力,且与肿瘤形成呈正相关。还发现lncRNA H19在NSCLC组织和细胞中的表达也升高。H19的表达在体内外均与肿瘤生长相关,且H19通过介导miR-29b-3p的表达来调节PGRN。
H19和PGRN可作为NSCLC的生物标志物和治疗靶点。