Front Genet. 2021 Oct 18;12:738559. doi: 10.3389/fgene.2021.738559. eCollection 2021.

MiR-320d Inhibits Progression of EGFR-Positive Colorectal Cancer by Targeting TUSC3

Zhu Yufeng  1 Qi Ming  2 Wu Dandan  3 Affiliations

Free PMC article

Abstract

Background: The mechanism of miR-320d in EGFR-positive colorectal cancer (CRC) has not been fully elucidated. The aim of the present study was to explore the molecular mechanism of miR-320d in CRC. Methods: The miRNA microarray analysis was conducted to identify differential expressed miRNAs. The expression of miR-320d was validated using quantitative real-time PCR. EGFR-positive CRC cells were transfected with miR-320d mimic and inhibitor, after which cell proliferation, migration, and invasion were assayed. The relationship between miR-320d and TUSC3 was confirmed using bioinformatics and dual-luciferase reporter gene assays. Proteins involved in signaling pathways and the epithelial-mesenchymal transition were detected with Western blot. Results: We found that the miR-320d expression is associated with tumor size and distant metastasis in colorectal cancer. Overexpression of miR-320d in EGFR-positive HCT-116 and SW480 cells decreased not only the proliferation ability but also the invasion and migration ability. In addition, miR-320d had the ability to inhibit epithelial-to-mesenchymal transition. Luciferase assays revealed that miR-320d directly targets the 3′-UTR of TUSC3. TUSC3 was downregulated by miR-320d at both the protein and mRNA levels in EGFR-positive CRC cell lines. Conclusion: Generally, our results demonstrated that miR-320d could inhibit the malignant phenotype of EGFR-positive CRC through targeting TUSC3. The miR-320d might be a potential therapeutic target for EGFR-positive CRC.

Keywords: colorectal cancer; epidermal growth factor receptor; miR-320d; tumor; tumor-suppressor candidate 3.

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