Wang Lei, Xu Minyi, Lu Pei, Zhou Fangfang
Department of Clinical Laboratory, Shanghai Eighth People's Hospital, Xuhui Branch of Shanghai Sixth People's Hospital, Shanghai 200235, People's Republic of China,
Onco Targets Ther. 2018 Dec 12;11:9013-9025. doi: 10.2147/OTT.S183847. eCollection 2018.
In recent years, microRNAs (miRNAs) have been reported to be aberrantly expressed in colorectal cancer (CRC). The deregulation of miRNAs is implicated in the formation and progression of CRC, and participates in the regulation of a wide range of biological behaviors. Considering the crucial role of miRNAs in CRC, miRNAs are thought to have significant promise in the diagnosis and therapy of patients with this malignancy.
Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect miR-769 expression in CRC tissues and cell lines. MTT assay and flow cytometry analysis were used to determine the effects of miR-769 upregulation in CRC cell proliferation and apoptosis, respectively. The influence of miR-769 overexpression in CRC cell migration and invasion was evaluated through migration and invasion assays. Notably, the possible mechanisms underlying the action of miR-769 in CRC cells were explored.
In the present study, miR-769 was frequently found to be poorly expressed in CRC tissues and cell lines. Functional assays showed that recovery of miR-769 expression suppressed CRC cell proliferation, migration, and invasion, increased cell apoptosis in vitro, and inhibited tumor growth in vivo. Cyclin-dependent kinase 1 (CDK1) was the direct target of miR-769 in CRC cells. CDK1 was overexpressed in CRC tissue samples and negatively correlated with miR-769 expression. In addition, CDK1 inhibition imitated the tumor suppressor activity of miR-769 in CRC cells, and restoration of CDK1 expression partially abolished the tumor-suppressing roles of miR-769 in malignant CRC cells.
The results of this study demonstrated that miR-769 was downregulated in CRC and directly targeted CDK1 to be implicated in the regulation of CRC cell proliferation, apoptosis, migration and invasion. Thus, the miR-769/CDK1 axis might be an effective therapeutic target for treating patients with CRC.
近年来，据报道微小RNA（miRNA）在结直肠癌（CRC）中表达异常。miRNA的失调与CRC的形成和进展有关，并参与多种生物学行为的调节。鉴于miRNA在CRC中的关键作用，人们认为miRNA在这种恶性肿瘤患者的诊断和治疗中具有巨大潜力。
采用逆转录定量聚合酶链反应（RT-qPCR）检测CRC组织和细胞系中miR-769的表达。分别用MTT法和流式细胞术分析来确定miR-769上调对CRC细胞增殖和凋亡的影响。通过迁移和侵袭实验评估miR-769过表达对CRC细胞迁移和侵袭的影响。值得注意的是，还探索了miR-769在CRC细胞中发挥作用的潜在机制。
在本研究中，经常发现miR-769在CRC组织和细胞系中低表达。功能实验表明，恢复miR-769表达可抑制CRC细胞增殖、迁移和侵袭，增加体外细胞凋亡，并抑制体内肿瘤生长。细胞周期蛋白依赖性激酶1（CDK1）是miR-769在CRC细胞中的直接靶点。CDK1在CRC组织样本中过表达，且与miR-769表达呈负相关。此外，抑制CDK1可模拟miR-769在CRC细胞中的肿瘤抑制活性，恢复CDK1表达可部分消除miR-769在恶性CRC细胞中的肿瘤抑制作用。
本研究结果表明，miR-769在CRC中表达下调，并直接靶向CDK1参与CRC细胞增殖、凋亡、迁移和侵袭的调节。因此，miR-769/CDK1轴可能是治疗CRC患者的有效治疗靶点。
