Background: Prostate cancer is the most common malignant tumor in men. Due to the lack of theoretical research on its pathogenic mechanism, the current cure rate is still low. miRNAs play an important role in the pathogenesis of various cancers. miRNA-214-5p plays an important role in the development of a variety of cancers. This study aims to explore the expression level of miR-214-5p in prostate cancer and make a preliminary study of its molecular mechanism in the development of prostate cancer to provide effective new strategies for the treatment of prostate cancer.
Methods: The target genes of miRNA-214-5p were predicted with bioinformatics technology, and the target relationship between miRNA-214-5p and its target genes was verified with dual luciferase reporter assay. RT-qPCR and Western blot were used to detect the expression levels of miRNA-214-5p and target genes in 50 clinical samples and two common prostate continuous cell lines, respectively. The targeting relationship between miRNA-214-5p and its target genes was verified with clinical data. miRNA-214-5p and miRNA-214-5p inhibitor was over-expressed in DU-145 cell lines to verify the effect of miRNA-214-5p on prostate cancer cell proliferation and SOX4 gene expression. And the mechanism of miRNA-214-5p inhibiting the proliferation of prostate cancer cells were analyzed by detecting the expression difference of downstream factors of SOX4 pathway. Bioinformatics analysis showed that miRNA-214-5p combined with SOX4 3'UTR region, and dual luciferase reporter assay further verified the reliability of the predicted results. The low expression of miRNA-214-5p was observed in prostate cancer tissues and cells, while high expression of SOX4 was observed in prostate cancer tissues and cells.
Results: Overexpression of miRNA-214-5p to prostate cancer cells significantly inhibited the proliferation of cancer cells, and the expression of SOX4 was inhibited in the transfected cell line. After transfection of miRNA-214-5p inhibitor into prostate cancer cells, the cell proliferation rate further increased. Meanwhile, overexpression of miRNA-214-5p effectively inhibited the expression of SOX4 downstream factors, including c-Myc, eIF4E, and CDK4. However, the specific knockdown of SOX4 through SOX4 shRNA significantly reduced the proliferation of prostate cancer cell lines.
Conclusions: miRNA-214-5 can inhibit the proliferation of prostate cancer cells by specifically targeting S0X4 and inhibiting the expression of growth factors downstream of this pathway.
Keywords: Prostate cancer; SOX4; miRNA-214-5p.
© 2021. The Author(s).