Downregulation of miR-216a-5p by long noncoding RNA PVT1 suppresses colorectal cancer progression via modulation of YBX1 expression

Cancer Manag Res. 2019 Jul 24;11:6981-6993. doi: 10.2147/CMAR.S208983. eCollection 2019.


Purpose: Increasing evidence has demonstrated that microRNAs (miRNAs) are closely related to the occurrence and development of tumors. MiR-216a-5p, located at 2p16.1, has been shown to suppress proliferation of cancerous cells. However, its expression and function in colorectal cancer (CRC) remain unclear.

Materials and methods: The significance of miR-216a-5p in CRC was studied by analyzing miR-216a-5p expression in CRC tissues and its association with clinicopathological parameters. CRC cells, stably overexpressing miR-216a-5p, were evaluated for cell proliferation and metastasis using cell counting kit-8 (CCK-8) and transwell assay methods. Epithelial-mesenchymal transition (EMT) pathway was analyzed by Western blotting. Bioinformatics, quantitative real-time polymerase chain reaction (RT-qPCR), and luciferase reporter assay were performed to define the regulation of PVT1/miR-216a-5p/Y Box Binding Protein 1 (YBX1) axis in CRC.

Results: The expression of miR-216a-5p was found to be significantly downregulated in CRC and was correlated with the various stages and differentiation degree of the tumors. Moreover, the overexpression of miR-216a-5p could significantly inhibit the tumor growth, metastasis, and EMT progression in CRC. Furthermore, the expression of miR-216a-5p was negatively correlated with the expression of PVT1, and PVT1 could reverse tumor suppressive effect of miR-216a-5p in CRC cells. Finally, YBX1 might be the key target of PVT1/miR-216a-5p axis in CRC.

Conclusion: Downregulation of miR-216a-5p by PVT1 could suppress CRC progression via modulating YBX1 expression.

Keywords: PVT1; YBX1; colorectal cancer; epithelial–mesenchymal transition; metastasis; miR-216a-5p.