miR-7 inhibits the invasion and metastasis of gastric cancer cells by suppressing epidermal growth factor receptor expression

Abstract

The present study profiled differentially expressed microRNAs (miRs) in gastric cancer cell lines and then investigated miR-7 expression in gastric cancer tissue specimens and the effects of miR-7 on the growth, invasion and metastasis of gastric cancer cells and the underlying molecular events. A microRNA microarray was used to profile differentially expressed miRNAs in human gastric cancer cell lines relative to a normal stomach mucosal epithelial cell line. The miRNA miR-7 was selected for further investigation, which included real-time reverse-transcription PCR (qRT-PCR) analysis of miR-7 levels in different gastric cancer cell lines and tissues and distant non-tumor tissues from patient resections. Cell counting kit-8 (CCK-8), Transwell migration and invasion, and western blot assays were performed to assess tumor cell viability, invasion and gene expression, respectively, after miR-7 transfection. The miRNA microarray profiling revealed 14 upregulated miRNAs (including miR-21, miR-26b and miR-30b) and 19 downregulated miRNAs (including let-7i, miR-7 and miR-622) between gastric cancer and normal cell lines. The qRT-PCR analysis confirmed that reduced miR-7 expression occurred more frequently in poorly and moderately differentiated gastric cancer MGC-803, MKN-45 and SGC-7901 cell lines than in the well-differentiated gastric cancer NCI-N87 cell line, which was consistent with the results for gastric cancer tissues. Expression of miR-7 was downregulated in 86.9% (20/23) of the gastric cancer tissues compared with that in the distant non-tumor tissues. Restoration of miR-7 expression significantly inhibited tumor cell viability, invasiveness and migration when compared with the control cells. Luciferase assay confirmed the epidermal growth factor receptor (EGFR) as a target gene of mR-7, and expression of miR-7 significantly suppressed EGFR expression at both the mRNA and protein levels. The data from the present study demonstrated that reduced miR-7 expression contributes to gastric cancer development and progression. Further study will investigate miR-7 in the regulation of EGFR expression in vitro and in vivo.

Significance of microRNA 21 in gastric cancer

“…Comparative microarray profiling of gastric cancer and normal cell lines revealed differential expression of 14 miRNAs, including miR-21, miR-26b and miR-30b that are upregulated and 19 miRNAs, including let-7i, miR-7, miR-622 were downregulated in gastric cancer [27]. Zhang et al [28] demonstrated that overexpression of miR-21 in the gastric cancer cell line, AGS enhanced the proliferation and invasive ability of cells.…”

Role of microRNA-7 in digestive system malignancy

“…Another two studies reported that miR-7 was expressed at a high level during human pancreatic islet development [10,17] . For malignancy, it has been demonstrated that miR-7 is downregulated in cancer tissue of digestive malignancies such as GC [18][19][20] , CRC [21,22] and hepatocellular carcinoma (HCC) [23] by comparison with normal tissues, suggesting that it acts as a suppressor. A similar conclusion was drawn in a study of hydroxycamptothecin-resistant GC cells [24] .…”

“…MiR-7 suppresses GC cell invasion and metastasis both in vitro and in vivo by targeting the miR-7/insulin-like growth factor 1 receptor/Snail axis, which shows its EMT function and suggests that it can act as a therapeutic biomarker to prevent GC metastasis [18] . Xie et al [19] demonstrated that restoration of miR-7 significantly inhibited tumor cell viability, invasion and migration by suppressing EGFR expression. These results suggest that targeting miR-7 is a potential therapeutic option for GC (Figure 1).…”

MicroRNA-509-3p inhibits cancer cell proliferation and migration by targeting the mitogen-activated protein kinase kinase kinase 8 oncogene in renal cell carcinoma

“…To date, ~2,000 human miRNAs have been identified, which are involved in the regulation of biological processes, including proliferation, apoptosis, migration and differentiation (8). Several miRNAs have been implicated as oncogenes or as tumor suppressors, and are aberrantly expressed in various types of cancer, including RCC (9)(10)(11)(12). Previous studies have demonstrated, through transfection with pre-miR-509-3p in vitro, that miR-509-3p is downregulated in RCC, which is associated with cell proliferation and migration in 786-O RCC cells.…”