Department of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Collaborative Innovation Center for Cancer Personalized Medicine, No. 42, Baiziting, Xuanwu district, Nanjing, 210009, China.
The Fourth Clinical College of Nanjing Medical University, Nanjing, 210009, China.
Apoptosis. 2021 Jun;26(5-6):261-276. doi: 10.1007/s10495-021-01665-1. Epub 2021 Mar 29.
Accumulated evidence has demonstrated that miRNAs are closely implicated in lung carcinogenesis. Herein, we explored the expression pattern of miR-30b-5p in lung cancer, and aimed to uncover miR-30b-5p roles in lung cancer progression and drug resistance. miR-30b-5p expression profiles in lung cancer tissues and the matched non-tumor tissues were determined by using qPCR. Cell viability, migration, invasion and in vivo tumorigenesis were determined by using the CCK-8, colony formation, wound healing, transwell chambers experiments and tumor xenograft models. RNA immunoprecipitation (RIP) and dual luciferase reporter experiments were applied to evaluate the relationship between miR-30b-5p and LRP8. The results demonstrated that miR-30b-5p showed a low expression profile in lung cancer tissues and cells, and closely linked to poor prognosis and malignant clinical process. Cell viability, migration, invasiveness and tumorigenesis were significantly weakened following miR-30b-5p overexpression in A549 and NCI-H1299 cells, while cell apoptosis rates were increased. In addition, miR-30b-5p was lowly expressed in A549/DDP (a cisplatin drug resistant cell line) as compared with A549 cells, and miR-30b-5p increased A549/DDP cell sensitivity to DDP. However, these above roles of miR-30b-5p were all significantly impaired following the overexpression of LRP8 which was overexpressed in lung cancer tissues. Collectively, this study demonstrated that miR-30b-5p functions as a tumor suppressor in lung cancer, and re-sensitizes lung cancer cells to DDP by targeting LRP8.
已有大量证据表明,miRNAs 与肺癌的发生密切相关。在此,我们研究了 miR-30b-5p 在肺癌中的表达模式,并旨在揭示 miR-30b-5p 在肺癌进展和耐药中的作用。通过 qPCR 测定肺癌组织和配对非肿瘤组织中的 miR-30b-5p 表达谱。通过 CCK-8、集落形成、划痕愈合、Transwell 室实验和肿瘤异种移植模型测定细胞活力、迁移、侵袭和体内肿瘤发生。应用 RNA 免疫沉淀(RIP)和双荧光素酶报告实验评估 miR-30b-5p 与 LRP8 之间的关系。结果表明,miR-30b-5p 在肺癌组织和细胞中表达水平较低,与不良预后和恶性临床过程密切相关。在 A549 和 NCI-H1299 细胞中转染 miR-30b-5p 后,细胞活力、迁移、侵袭和肿瘤发生明显减弱,而细胞凋亡率增加。此外,与 A549 细胞相比,A549/DDP(顺铂耐药细胞系)中的 miR-30b-5p 表达水平较低,miR-30b-5p 增加了 A549/DDP 细胞对顺铂的敏感性。然而,在肺癌组织中过表达 LRP8 后,miR-30b-5p 的这些作用均显著受损。综上所述,本研究表明 miR-30b-5p 在肺癌中作为一种肿瘤抑制因子发挥作用,通过靶向 LRP8 使肺癌细胞重新对 DDP 敏感。