Li Tao, Wang Xiuxiu, Jing Lijun, Li Yu
Department of Respiratory Diseases, Qilu Hospital of Shandong University, Jinan, China.
Front Oncol. 2019 Mar 1;9:120. doi: 10.3389/fonc.2019.00120. eCollection 2019.
Lung adenocarcinoma (LUAD) is one of the most lethal malignancies, posing a threat to human health. However, the molecular mechanisms underlying LUAD development remain largely unknown. In this study, we found that miR-1-3p was significantly downregulated in human LUAD tissues and cell lines and played an inhibitory role in LUAD cell tumorigenesis, as evidenced by the significantly reduced viability, migration, and invasion of LUAD cells in response to miR-1-3p overexpression. Mechanistically, microRNA (miR)-1-3p physically interacted with the 3'-untranslated region (UTR) of protein regulator of cytokinesis 1 (PRC1) mRNA, leading to downregulation of PRC1. Overexpression of PRC1 reversed the inhibitory effects of miR-1-3p on LUAD cell tumorigenesis, suggesting that the miR-1-3p/PRC1 axis is majorly involved in suppressing LUAD development and progression. Consistently, PRC1 was dramatically induced in LUAD tissues and cell lines as well as associated with a poor prognosis in LUAD patients. Taken together, our study identified the miR-1-3p/PRC1 axis as an important regulatory mechanism contributing to LUAD inhibition and provided valuable clues for the future development of therapeutic strategies against LUAD.
肺腺癌（LUAD）是最致命的恶性肿瘤之一，对人类健康构成威胁。然而，LUAD发生发展的分子机制仍 largely未知。在本研究中，我们发现miR-1-3p在人LUAD组织和细胞系中显著下调，并在LUAD细胞肿瘤发生中发挥抑制作用，miR-1-3p过表达导致LUAD细胞的活力、迁移和侵袭显著降低即证明了这一点。机制上，微小RNA（miR）-1-3p与胞质分裂1蛋白调节因子（PRC1）mRNA的3'-非翻译区（UTR）发生物理相互作用，导致PRC1下调。PRC1过表达逆转了miR-1-3p对LUAD细胞肿瘤发生的抑制作用，提示miR-1-3p/PRC1轴主要参与抑制LUAD的发生发展。同样，PRC1在LUAD组织和细胞系中显著诱导表达，并且与LUAD患者的不良预后相关。综上所述，我们的研究确定miR-1-3p/PRC1轴是促进LUAD抑制的重要调节机制，并为未来开发针对LUAD的治疗策略提供了有价值的线索。
