DNA methylation‐regulated and tumor‐suppressive roles of miR‐487b in colorectal cancer via targeting MYC, SUZ12, and KRAS

MiR‐487b is a CRC suppressor that prevents the EMT process and targets to MYC, SUZ12, and KRAS to inhibit the proliferation, migration, and invasion of CRC cells. Meanwhile, DNA methylation might be the reason for the aberrantly low expression of miR‐487b in CRC. Thus, miR‐487b is identified as a diagnosis‐related biomarker and a novel target for CRC therapy.

Abstract

Human colorectal cancer (CRC), characterized by its high morbidity and lethality, seriously threatens human health and lives. MicroRNA‐487b (miR‐487b) is currently reported to be aberrantly expressed in several tumors, but the detailed functions and underlying mechanisms of miR‐487b in CRC remain unclear. Here, we found that miR‐487b is downregulated in CRC cell lines and is markedly decreased in tumor specimens derived from CRC patients. MiR‐487b inhibits cell proliferation, migration and invasion and promotes the apoptosis of CRC cells in vitro. Statistical analysis of clinical samples indicates that miR‐487b may serve as a biomarker for early CRC diagnosis. Inverse correlations between the expression levels of MYC, SUZ12, and KRAS and that of miR‐487b exist in vitro and in CRC patient tissue specimens. Further experiments demonstrated the regulatory effects of miR‐487b on MYC, SUZ12, and KRAS, and the disruption of these genes partially restores the miR‐487b inhibitor‐induced phenotype. Additionally, miR‐487b promoter region is in a DNA hypermethylated condition and the DNA methyltransferase inhibitor 5‐aza‐2'‐deoxycytidine (5‐Aza) increases the levels of miR‐487b but suppresses the expression of MYC, SUZ12, and KRAS in a time‐ and concentration‐dependent manner in CRC cells. Collectively, miR‐487b is regulated by DNA methylation and it functions as a tumor suppressor in CRC mainly through targeting MYC, SUZ12, and KRAS. Our study provides insight into the regulatory network in CRC cells, offering a new target for treating CRC patients.

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