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

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.

MicroRNA Expression Signatures in Clear Cell Renal Cell Carcinoma: High-Throughput Searching for Key miRNA Markers in Patients from the Volga-Ural Region of Eurasian Continent

“…However, miRNA-487b was shown to be downregulated in osteosarcoma CD133 positive cell lines [ 40 ] and inhibited osteosarcoma chemoresistance and metastasis [ 41 ]. The suppressive role of miRNA-487b was also indicated in colorectal cancer via targeting MYC, SUZ12 and KRAS [ 42 ]. On the other hand, in hepatocellular carcinoma, higher miRNA-487b expression was observed in the serum of HCC patients compared with healthy individuals, and was associated with poor prognosis [ 43 ].…”

chi-miR-487b-3p Inhibits Goat Myoblast Proliferation and Differentiation by Targeting IRS1 through the IRS1/PI3K/Akt Signaling Pathway

“…Some studies have reported miR-487b-3p as a tumor suppressor that inhibits osteosarcoma chemoresistance and metastasis by targeting ALDH1A3 [ 31 ]. miR-487b may participate in the interaction between GRM3 and TGF-β, and restrain the proliferation and metastasis of CRC cells [ 32 ]. Moreover, miR-487b-3p was also reported to be capable of preventing cell proliferation and differentiation in C2C12 myoblasts by targeting IRS1 [ 18 ].…”

Increased Expression of miR-487b Is Associated With Poor Prognosis and Tumor Progression of HBV-Related Hepatocellular Carcinoma

“…Previous research has shown that abnormal miRNA expression in serum could be used as a biomarker for cancer. Work by Chen et al established that miR-487b was significantly downregulated in metastatic tissues compared with matched tumor tissues and that miR-487b can be regarded as a biomarker for early colorectal cancer diagnosis and a criterion to judge metastasis [ 24 ]. Another study by Wang et al illustrated that miR-487b played an oncogenic role in osteosarcoma progression via directly targeting TRAK2, which could advance the development of cancer treatment [ 25 ].…”