microRNA-124 inhibits proliferation and induces apoptosis by directly repressing EZH2 in gastric cancer

Abstract

MicroRNA-124 (miR-124), a pivotal member of the p53 network, was found to be down-regulated in multiple types of tumors and further reported as tumor suppressor microRNA. In this study, we found that miR-124 was down-regulated in gastric cancer cell lines and specimens. Restoration of miR-124 expression inhibited the proliferation and colony formation of gastric cancer cells. EZH2 (enhancer of zeste homolog 2), which has been shown to be an important transcription factor involved in the proliferation and metastasis of tumor cells, was here confirmed to be a direct target gene of miR-124. On the other hand, silencing EZH2 also inhibits cell proliferation of gastric cancer cells. Furthermore, the treatment combining miR-124 with 5-fluorouracil (5-FU) significantly showed more efficient anti-tumor effects than single treatment of miR-124 or 5-FU, and over-expression of miR-124 suppresses the tumor growth in vivo. Our study indicate that miR-124 can suppress gastric cancer cell growth by directly targeting the EZH2 gene and sensitize the treatment effect of 5-FU. Therefore, miR-124 shows tumor-suppressive activity and may be a new and useful approach of gastric cancer therapy.

Lentivirus-mediated overexpression of miR-124 suppresses growth and invasion by targeting JAG1 and EZH2 in gastric cancer

“…The present study also determined that EZH2 was upregulated in GC tissues compared with corresponding normal gastric tissues. Silencing EZH2 has also been found to inhibit the proliferation of GC cells and the invasive ability of hepatocellular carcinoma (HCC) cells (10,21). Epithelial-mesenchymal transition is known to be a key event in the invasion and metastasis of cancer cells (10,30).…”

“…Silencing EZH2 has also been found to inhibit the proliferation of GC cells and the invasive ability of hepatocellular carcinoma (HCC) cells (10,21). Epithelial-mesenchymal transition is known to be a key event in the invasion and metastasis of cancer cells (10,30). Owing to the effects of miR-124 on GC cell migration and invasion, fibronectin and vimentin, as the mesenchymal markers, were detected in GC cells transduced with Lenti-miR-124.…”

“…Overexpression of miR-124 repressed the expression of the JAG1 and EZH2 in GC cell lines. JAG1 and EZH2 have been reported to be targets of miR-124 (7,10,21). JAG1 and EZH2 protein expression levels were downregulated by overexpression of miR-124 in SGC-7901 and AGS GC cell lines (Fig.…”

“…Recently, miR-124 has been found down-regulated in multiple tumor types, including cancer (6), prostate (7), lung (8) and colorectal cancer (9). It also been found that miR-124 could inhibit the proliferation of GC cells proliferation by targeting Rho-associated protein kinase 1, enhancer of zeste homolog 2 (EZH2) and sphingosine kinase 1 (SPHK1) (10)(11)(12). A previous study demonstrated that overexpression of miR-124 by transfection with miR-124 mimics could inhibit GC cell growth, migration and invasion, and induce cell cycle arrest by directly targeting the Notch ligand Jagged1 (JAG1) in vitro (13).…”

Chromatin Memory in the Development of Human Cancers

“…Enhancer of zeste (EZH)2, a methyltransferase component of polycomb repressive complex 2(PRC2) has been found deregulated in many sorts of cancers, including lymphoma [148,149], bladder [150][151][152][153], gastric [154,155], lung [156], breast cancers [157][158][159]. EZH2 catalyzes H3K27me3 in the presence of suppressor of zeste 12 (SUZ12) and embryonic ectoderm development (EED) which possess a carboxy-terminal domain specifically recognizes histone tails that carry trimethyl-lysine residues [160].…”