microRNA-769 is downregulated in colorectal cancer and inhibits cancer progression by directly targeting cyclin-dependent kinase 1
Authors Wang L, Xu M, Lu P, Zhou F
Received 14 August 2018
Accepted for publication 10 October 2018
Published 12 December 2018 Volume 2018:11 Pages 9013—9025
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Justinn Cochran
Peer reviewer comments 2
Editor who approved publication: Dr Yao Dai
Lei Wang, Minyi Xu, Pei Lu, Fangfang Zhou
Department of Clinical Laboratory, Shanghai Eighth People’s Hospital, Xuhui Branch of Shanghai Sixth People’s Hospital, Shanghai 200235, People’s Republic of China
Background: 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.
Material and methods: 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.
Results: 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.
Conclusion: 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.
Keywords: colorectal cancer, microRNA-769, proliferation, apoptosis, metastasis, cyclin-dependent kinase 1
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