Medical Image Institute, Guizhou Medical University, Guiyang, Guizhou, China.
Eur Rev Med Pharmacol Sci. 2019 Jan;23(2):679-689. doi: 10.26355/eurrev_201901_16881.
MicroRNA (miRNA) plays vital roles in the development of different cancers. In the current work, we explored the function of miR-126-3p in the growth and metastasis of non-small-cell lung cancer (NSCLC) cell in vitro and in vivo.
The expressions of miR-126-3p in NSCLC cell lines were assessed using the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation, wound healing and transwell invasion were applied to reveal the role of miR-126b-3p on NSCLC cell growth, migration and invasion. The expressions of epithelial-mesenchymal transition (EMT) associated markers (E-cadherin and N-cadherin) were assessed by immunofluorescence staining. The Xenograft model and lung metastasis model were applied to explore the impact of miR-126-3p on the growth and aggressiveness of NSCLC cell in vivo.
MiR-126-3p was significantly down-regulated in NSCLC cell lines and tissues. The up-regulation of miR-126-3p inhibited the growth, colony formation, migration and invasion of NSCLC cell. Furthermore, the xenograft model indicated that miR-126-3p suppressed NSCLC cell growth and lung metastasis by targeting chemokine (C-C motif) receptor 1 (CCR1). In addition, we demonstrated that the over-expression of CCR1 rescued the inhibitory effects of miR-126-3p on NSCLC cells growth, migration and invasion. Finally, knocked-down of CCR1 was able to mimic the inhibitory effects of miR-126-3p on the progression of NSCLC cell.
These findings indicate that miR-126-3p plays an important role in the growth, migration and invasion of NSCLC by targeting CCR1.
微小 RNA(miRNA)在不同癌症的发展中起着至关重要的作用。在目前的工作中,我们探讨了 miR-126-3p 在体外和体内非小细胞肺癌(NSCLC)细胞生长和转移中的功能。
采用定量实时聚合酶链反应(qRT-PCR)检测 NSCLC 细胞系中 miR-126-3p 的表达。采用 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四唑溴盐(MTT)、集落形成、划痕愈合和 Transwell 侵袭实验揭示 miR-126b-3p 对 NSCLC 细胞生长、迁移和侵袭的作用。通过免疫荧光染色检测上皮-间充质转化(EMT)相关标志物(E-钙粘蛋白和 N-钙粘蛋白)的表达。应用异种移植模型和肺转移模型探讨 miR-126-3p 对 NSCLC 细胞体内生长和侵袭的影响。
miR-126-3p 在 NSCLC 细胞系和组织中明显下调。上调 miR-126-3p 抑制 NSCLC 细胞的生长、集落形成、迁移和侵袭。此外,异种移植模型表明,miR-126-3p 通过靶向趋化因子(C-C 基序)受体 1(CCR1)抑制 NSCLC 细胞生长和肺转移。此外,我们证明 CCR1 的过表达可挽救 miR-126-3p 对 NSCLC 细胞生长、迁移和侵袭的抑制作用。最后,敲低 CCR1 能够模拟 miR-126-3p 对 NSCLC 细胞进展的抑制作用。
这些发现表明,miR-126-3p 通过靶向 CCR1 在 NSCLC 的生长、迁移和侵袭中发挥重要作用。