microRNA-155 is downregulated in gastric cancer cells and involved in cell metastasis

Abstract

Abstract. , an important multifunctional microRNA, has been implicated in the development of multiple solid tumors, yet, its role in gastric cancer cells has not been fully elucidated. In this study, we find that miR-155 was significantly downregulated in gastric cancer cell lines compared with an immortalized gastric epithelial cell line (GES-1). Overexpression of miR-155 in SGC-7901 and MKN-45 gastric cancer cells dramatically suppressed cell migration, invasion and adhesion in vitro. Overexpression of miR-155 significantly reduced the protein levels of SMAD2 and repressed the activity of a luciferase reporter containing one of the two predicted miR-155 binding sites in SMAD2 3'-UTR, indicating that SMAD2 may be a miR-155 target gene. miR-155 expression was also remarkably restored by a DNA demethylating agent (5-Aza-2-deoxycytidine) in SGC-7901 and MKN-45 gastric cancer cells. Taken together, these data suggest that miR-155 may function as a tumor suppressor to regulate gastric cancer cell metastasis by targeting SMAD2, and its downregulation in gastric cancer cells may be partly ascribed to DNA methylation. IntroductionGastric cancer remains the fourth most common malignancy and the second leading cause of cancer-related death in both genders worldwide, despite a substantial decrease in its rate (1,2). In 2008, more than 70% of new cases (713,000 cases) occurred in developing countries, and half the world total occured in Eastern Asia (mainly in China) (2). Despite a steady decline in mortality, the prognosis of patients with advanced gastric cancer is still very disappointing (3), mainly due to poor understanding of the mechanisms underlying its development. microRNAs (miRNAs) are endogenous, small (18-25 nucleotides), non-coding RNAs that play important roles in gene expression by targeting 3'UTR of cellular transcripts, resulting mRNA cleavage or translational inhibition (4,5). By these mechanisms, miRNAs have been shown to be involved in mediating processes in tumorigenesis such as cell cycle regulation, differentiation, apoptosis, invasion and metastasis (6,7). Dysregulated expression of miRNAs is now considered as a common characteristic of all human tumors (8). The aberrant expression of miRNAs in human cancers and their role in tumor formation might define miRNAs as oncogenes or tumor suppressors.miR-155, processed from an exon of a non-coding RNA transcribed from the B-cell integration cluster (BIC), has been a typical multifunctional miRNA (9,10). Accumulating evidence has demonstrated that miR-155 is involved in numerous biological processes including haematopoiesis, inflammation, immunity and carcinogenesis (10,11). Several lines of evidence indicate that dysregulation of miR-155 is linked to various solid tumors, including breast, colon, cervical, thyroid, pancreatic and lung cancer (12-18). The frequently detected overexpression of miR-155 in these tumors indicates a major role of an oncogene; however, possible tumor suppressor functions have also been reported (19-21). Although miR-155 has bee...

Long non-coding RNA CCAT1 is overexpressed in oral squamous cell carcinomas and predicts poor prognosis

“…The presented results suggested that CCAT1 overexpression was likely to affect the downstream target miRNA level in oral tumors via sponging mechanism as shown in other cancers (9,14). In addition, CCAT1 overexpressed samples expressed a low level of miR155 and let7b and the same has been frequently reported to be deregulated in several cancer cell lines and cancers (31). All these observations suggest that CCAT1 overexpression may serve an important role in oral carcinogenesis and treatment response.…”

Down‐regulated miR‐625 suppresses invasion and metastasis of gastric cancer by targeting ILK

“…It has been confirmed that the development and progression of gastric cancer may be attributed to miRNAs [4][5][6][7][8]. In our previous work, by comparing the miRNA expression profile in 28 gastric cancer tissues and their adjacent non-tumor tissues, we found numerous putative miRNAs of differential expression [9,10]. Of them in addition to the well-known miRNAs, such as miR-375, miR-29c, miR-31, miR-199-3p, miR-409-3p [11] and miR-200 family, we noticed that miR-625 was rarely researched and was one of the most significantly down-regulated miRNAs in gastric cancer.…”

Mechanisms of MicroRNA Deregulation and MicroRNA Targets in Gastric Cancer

“…miR-137 is related to CDC42 inactivation and inhibition of cell growth and induction of apoptosis in gastric cancer cells [29]. In gastric cancers, miR-155 is methylated and down-regulated and conversely, overexpression of miR-155 can inhibit cell migration, invasion, and adhesion by targeting 3' UTR of SMAD2 in TGF-β pathway [30].CDK4, CCNF2, and CCNA2 are cell cycle-related genes that are targeted by miR34b and miR-34c, which are also silenced epigenetically by methylation in gastric cancers [31]. miR-129 is methylated and down-regulated in primary gastric tumors, leading to SOX4 gene being upregulated in gastric cancers.…”