Department of Respiratory Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Respiratory Medicine, People's Hospital of Rizhao Lanshan, Rizhao, China.
Neoplasma. 2018 Sep 19;65(5):779-789. doi: 10.4149/neo_2018_171130N778. Epub 2018 Jun 18.
Lung cancer remains the most common cause of tumor-related death worldwide. Recent studies have revealed that long non-coding RNAs (lncRNAs) are involved in the development of various cancers, including lung cancer. This study aimed to investigate the effect and the molecular basis of lncRNA PICART1 on lung cancer. We first assessed the PICART1 expression in lung cancer in vitro and vivo by qRT-PCR. Then the expression of PICART1 in SPC-A-1 and NCI-H1975 cell lines was inhibited and overexpressed by transient transfections. Thereafter, cell viability, cell cycle, migration and apoptosis were respectively measured by MTT, Transwell and flow cytometry assay. Furthermore, qRT-PCR and western blot analysis were mainly performed to assess the expression levels of apoptosis- and migration-related proteins and JAK2/STAT3 pathway proteins. Tumor formation was measured by xenograft tumor model assay in vivo. PICART1 expression was down-regulated in human lung cancer tissues and cell lines. Knockdown of PICART1 increased cell viability of lung cancer cell lines. However, PICART1 overexpression inhibited cell cycle progression and promoted apoptosis in SPC-A-1 and NCI-H1975 cell lines. PICART1 overexpression also inhibited migration, as evidenced by up-regulation of E-cadherin, and down-regulation of Twist1, MMP2 and MMP9. Furthermore, we found PICART1 inhibition may regulate cell apoptosis and migration through activating JAK2/STAT3 pathway. In vivo experiments revealed that PICART1 knockdown significantly promoted tumor formation. This study demonstrates that PICART1 overexpression represents an anti-growth and anti-metastasis role in lung cancer cells. Additionally, PICART1 acts as a tumor suppressor may be via regulation of JAK2/STAT3 pathway.
肺癌仍然是全球最常见的肿瘤相关死亡原因。最近的研究表明，长非编码 RNA（lncRNA）参与了各种癌症的发展，包括肺癌。本研究旨在探讨 lncRNA PICART1 对肺癌的影响及其分子机制。我们首先通过 qRT-PCR 评估了 lncRNA PICART1 在肺癌体外和体内的表达。然后通过瞬时转染抑制和过表达 SPC-A-1 和 NCI-H1975 细胞系中的 PICART1 表达。此后，分别通过 MTT、Transwell 和流式细胞术测定细胞活力、细胞周期、迁移和凋亡。此外，主要通过 qRT-PCR 和 Western blot 分析评估凋亡和迁移相关蛋白以及 JAK2/STAT3 通路蛋白的表达水平。体内通过异种移植肿瘤模型实验测定肿瘤形成。PICART1 在人肺癌组织和细胞系中表达下调。PICART1 敲低增加了肺癌细胞系的细胞活力。然而，PICART1 过表达抑制 SPC-A-1 和 NCI-H1975 细胞系的细胞周期进程并促进凋亡。PICART1 过表达还抑制迁移，表现为 E-钙黏蛋白上调和 Twist1、MMP2 和 MMP9 下调。此外，我们发现 PICART1 抑制可能通过激活 JAK2/STAT3 通路调节细胞凋亡和迁移。体内实验表明，PICART1 敲低显著促进肿瘤形成。本研究表明，PICART1 过表达在肺癌细胞中表现出抗生长和抗转移作用。此外，PICART1 作为肿瘤抑制因子可能通过调节 JAK2/STAT3 通路发挥作用。
