miR-218 suppresses gastric cancer cell proliferation and invasion via regulation of angiopoietin-2

Abstract

Novel targeted therapies need to be developed for gastric cancer, the third most common cancer type and the second most common cause of cancer-related mortality in China. Previous studies indicate that angiopoietin (Ang)-2 serves a role in the proliferation, migration, invasion and adhesion of malignant cells. The present study identified, using functional studies, that exogenous expression of miR-218 increased migration of NCI-87 and HGC-27 gastric cancer cells, which coincided with a reduction in the expression of Ang-2. In addition, intratumoral delivery of miR-218 inhibited proliferation and angiogenesis of gastric cancer cells in vivo, with a corresponding decreased in Ang-2 expression. These results indicate that miR-218 serves an important role in gastric cancer tumorigenesis through regulating the expression of Ang-2. Therefore, components of miR-218/Ang-2 signaling could provide novel therapeutic targets for the treatment of gastric cancer.

Insights into the Regulation of Tumor Angiogenesis by Micro-RNAs

“…miR-218 reduces VEGF expression in prostate cancer by acting on the mTOR component RICTOR (rapamycin-insensitive companion of mammalian target of rapamycin) and by blocking the RICTOR/mTOR/HIF-1/VEGF signaling pathway [110]. In gastric cancer, two targets of miR-218 have been identified: Angiopoietin-2 and ROBO1 (roundabout guidance receptor 1); their downregulation results in a reduction of tumor proliferation, invasion, and angiogenesis [111,112]. Moreover, low levels of miR-218 result in endothelial cell sprouting, motility, and tube formation [112].…”

miR‑218 promotes apoptosis of SW1417 human colon cancer cells by targeting c‑FLIP

“…miR-218 is also regarded as a tumor suppressor due to its function in the inhibition of invasion and growth of nasopharyngeal (31), oral (19), lung (15,32), and bladder (33) cancer cells. By regulating the expression of Ang-2 in gastric cancer cells NCI-87 and HGC-27, miR-218 overexpression suppressed cell proliferation and angiogenesis (17). An MTT assay revealed that miR-218 overexpression markedly suppressed the proliferation of gastric cancer cells and wound scratch assays indicated that miR-218 inhibited cell migration and EMT by targeting WASF3 (30).…”

“…In cultured gastric cancer cell lines SGC7901 and BGC823, it was revealed that miR-218 mRNA and protein expression were significantly decreased compared to those in normal gastric epithelial cell line GES-1 (30). Furthermore, compared with gastric cancer cell lines MGC80-3 and HGC-27, decreased miR-218 expression levels were also found in the more aggressive gastric cancer cell line NCI-87 (17). Notably, the present study revealed a significant decrease in miR-218 expression in human colon cancer tissues and SW1417 cells.…”

“…Notably, miRNAs have been reported to be involved in cancer development through their tumor-suppressing or -activating functions (11)(12)(13). Recently, miR-218 was reported to play a tumor-suppressive role in various types of human cancers, such as lung, bladder and gastric cancer, hepatocellular carcinoma, oral cancer and renal cell carcinoma (14)(15)(16)(17)(18)(19)(20), indicating that miR-218 may be a potential therapeutic target for the treatment of cancers.…”

Regulation of tumor angiogenesis by microRNAs: State of the art

“…MiR‐218, which is embedded in the introns of SLIT2 and SLIT3 (X. Zhang et al, ), is a tumor repressor miRNA that inhibits cell growth, invasion, migration, cancer stem‐like cell self‐renewal and angiogenesis (Tu et al, ; Uesugi et al, ; Yamasaki et al, ). Multiple studies have shown that miR‐218 is downregulated in several types of cancers (B. Guan et al, ; Tang, Wang, Zhang, & Li, ). Overexpression of miR‐218 leads to the inhibition of HUVECs migration, proliferation, and tube formation in vitro.…”