MiR-1224-5p acts as a tumor suppressor via inhibiting the malignancy of rectal cancer through targeting SLC29A3.

Na-Sha Song, Zhi-Dong Pei, Gui Fu

IUBMB life 2020 Oct

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The emphasis of our study was to determine the physiological function of miR-1224-5p in rectal cancer (RC) and its in-depth mechanism. First, the expression of miR-1224-5p in RC tissues was analyzed using public data from the TCGA database. Then, miR-1224-5p expression in RC cell lines SW480 and SW837 was measured using the qRT-PCR assay. The subsequent CCK-8 assay was executed to assess the function of miR-1224-5p in the viability of the RC cell. Bioinformatics prediction prompted that SLC29A3 may be a potential target gene for miR-1224-5p. Western blotting and dual-luciferase reporter assays were performed to affirm the above forecasting. Kaplan-Meier analysis and Cox multivariate analysis were carried out to assess the relationship between SLC29A3 and prognosis. Finally, CCK-8, colony formation assay, and transwell assay were used for functional analysis of miR-1224-5p/ SLC29A3 axis in vitro. MiR-1224-5p was expressed at low levels in RC tissues and cell lines. Up-regulation of miR-1224-5p inhibited SW480 cell viability, while inhibition of miR-1224-5p enhanced the viability of SW837 cells. What is more, we affirmed that miR-1224-5p could direct target SLC29A3, which was expressed at high levels in RC tissues. In addition, SLC29A3 could be used as an independent predictive factor of prognosis in patients with RC, and the higher SLC29A3 expression, the lower survival rate. Finally, cellular functional experiments evidenced that miR-1224-5p mimic can reduce the cell viability, invasion, and migration, while overexpression of SLC29A3 presented an opposite effect. Importantly, co-transfection experiments indicated that SLC29A3 can reverse miR-1224-5p-mediated inhibition in the malignant progression of RC cells. Our work raised the possibility that miR-1224-5p functioned as a tumor suppressor in RC, which achieved its function via targeting SLC29A3. © 2020 International Union of Biochemistry and Molecular Biology.

Citation

Na-Sha Song, Zhi-Dong Pei, Gui Fu. MiR-1224-5p acts as a tumor suppressor via inhibiting the malignancy of rectal cancer through targeting SLC29A3. IUBMB life. 2020 Oct;72(10):2204-2213