Downregulation of miR-654-3p in Colorectal Cancer Indicates Poor Prognosis and Promotes Cell Proliferation and Invasion by Targeting SRC

Zhang, Haoran and Shen, Zhanlong and Zhou, Yushi and Zhang, Zhen and Wang, Quan and Zhang, Mengmeng and Jiang, Kewei and Wang, Shan and Ye, Yingjiang and Wang, Bo (2020) Downregulation of miR-654-3p in Colorectal Cancer Indicates Poor Prognosis and Promotes Cell Proliferation and Invasion by Targeting SRC. Frontiers in Genetics, 11. ISSN 1664-8021

[thumbnail of pubmed-zip/versions/1/package-entries/fgene-11-577948/fgene-11-577948.pdf] Text
pubmed-zip/versions/1/package-entries/fgene-11-577948/fgene-11-577948.pdf - Published Version

Download (3MB)

Abstract

Background: MicroRNAs (miRNAs), such as miR-654-3p, regulate gene expression at the post-transcriptional level affecting malignant tumor behavior. However, the expression levels, function, and mechanism of miR-654-3p in colorectal cancer (CRC) are unknown.

Methods: The expression levels of miR-654-3p and SRC in 103 CRC tissues and matched normal colorectal tissues were detected by a quantitative real-time polymerase chain reaction (qRT-PCR). miR-654-3p was overexpressed by RNA mimics and SRC knockdown by siRNA. Function-based experiments were carried out to detect the proliferation and migration abilities in CRC cell lines. Flow cytometry assay was performed to evaluate the effect of miR-654-3p on cell apoptosis and cycle distribution. Xenograft tumor models in nude mice were utilized to evaluate miR-654-3p functions in vivo. Dual-fluorescence reporter assay was used to verify the direct binding between miR-654-3p and SRC.

Results: miR-654-3p was downregulated in CRC tissues as compared to matched normal colorectal tissues. The expression levels of miR-654-3p were closely associated with distant metastasis. In addition, elevated expression of miR-654-3p in CRC patients prolonged the overall survival. Upregulated miR-654-3p significantly suppressed the proliferation and migration capacity of CRC cells by enhancing apoptosis and promoting G0/G1 phase arrest. The direct binding between miR-654-3p and SRC was verified by the dual-luciferase reporter gene. Furthermore, the suppression of proliferation and migration capacity by elevated miR-654-3p level could be reversed by overexpressing SRC.

Conclusion: miR-654-3p acts as a tumor suppressor through regulating SRC. It might also serve as a diagnostic and prognostic indicator and a novel molecular target for CRC therapy.

Item Type: Article
Subjects: Lib Research Guardians > Medical Science
Depositing User: Unnamed user with email support@lib.researchguardians.com
Date Deposited: 06 Feb 2023 07:42
Last Modified: 11 Sep 2024 05:31
URI: http://eprints.classicrepository.com/id/eprint/73

Actions (login required)

View Item
View Item