Institute of Toxicology, Shenzhen Center for Disease Control and Prevention, No 8 Longyuan Road, Nanshan District, Shenzhen 518055, Guangdong, China.
Institute of Toxicology, Shenzhen Center for Disease Control and Prevention, No 8 Longyuan Road, Nanshan District, Shenzhen 518055, Guangdong, China.
Life Sci. 2019 Aug 15;231:116539. doi: 10.1016/j.lfs.2019.06.014. Epub 2019 Jun 6.
Although SET(I2PP2A) and miRNAs are reported to play a pivotal role in lung cancer, the underlying mechanisms have remained obscure. To address this issue, we investigated how miRNAs and SET participate in the progression of lung cancer.
miRNAs that target SET were predicted from multiple miRNA databases. Three human NSCLC cell lines and two normal lung cell lines were used to evaluate aberrant miRNA and SET expressions. A dual luciferase reporter assay system was employed to verify the interaction between miRNA and SET. Stable miRNA knockdown and SET overexpression in A549 cells were achieved through lentivirus transfection; the corresponding influences on lung cancer progression were also examined.
In this study, A549 was the sole cell line to lack SET/TAF-Iα expression, which was inversely correlated with the up-regulation of miR-21-5p. SET was subsequently revealed as the direct target site of miR-21-5p in A549 cells. The stable miR-21-5p knockdown and SET/TAF-Iα overexpression were shown to markedly enhance the expression of SET/TAF-Iα and to inhibit the migration, invasion, proliferation as well as the in vivo tumorigenicity of A549 cells.
We suggest that SET/TAF-Iα might be a tumor suppressing factor regulated by miR-21-5p in lung adenocarcinoma. This might provide a target for lung adenocarcinoma therapy.
尽管 SET(I2PP2A)和 miRNAs 被报道在肺癌中发挥关键作用,但潜在机制仍不清楚。为了解决这个问题,我们研究了 miRNAs 和 SET 如何参与肺癌的进展。
从多个 miRNA 数据库预测靶向 SET 的 miRNAs。使用三种人非小细胞肺癌细胞系和两种正常肺细胞系来评估异常的 miRNA 和 SET 表达。采用双荧光素酶报告基因检测系统来验证 miRNA 和 SET 之间的相互作用。通过慢病毒转染实现 A549 细胞中稳定的 miRNA 敲低和 SET 过表达,并检测其对肺癌进展的相应影响。
在这项研究中,A549 是唯一缺乏 SET/TAF-Iα 表达的细胞系,其表达与 miR-21-5p 的上调呈负相关。随后发现 SET 是 A549 细胞中 miR-21-5p 的直接靶标。稳定的 miR-21-5p 敲低和 SET/TAF-Iα 过表达显著增强了 SET/TAF-Iα 的表达,并抑制了 A549 细胞的迁移、侵袭、增殖以及体内致瘤性。
我们认为 SET/TAF-Iα 可能是肺腺癌中受 miR-21-5p 调控的肿瘤抑制因子。这可能为肺腺癌的治疗提供一个靶点。