Abstract
BackgroundGastric cancer is the second leading cause of cancer globally, and the mechanism of its pathogenesis is still largely unknown. Recently, non-coding RNAs have been recognized to promote metastasis in various cancers, including gastric cancer.MethodsWe found that metastasis associated lung adenocarcinoma transcript-1 (MALAT1) is upregulated in gastric cancer tissue compared to adjacent normal tissue, as determined by microarray and subsequent qRT-PCR, then investigated the impact of MALAT1 on apoptosis, cell proliferation, and the cell cycle to dissect the carcinogenesis of gastric cancer, and examined mechanisms of invasion and metastasis. Expression of MALAT1 and U6 was determined by SYBR qRT-PCR in nine-teen gastric cancer cell lines and fifty fresh samples of cancer tissue and adjacent tissues. Downregulation of MALAT1 was accomplished with two different siRNAs. Cell proliferation was determined after treatment with these siRNAs. FACS using PI/Annexin-V staining was carried out. To analyze the invasiveness, a scratch wound-healing assay and a Matrigel invasion assay were performed. Cancer related gene expression assay was done after transfection of siR- MALAT1.ResultsThe expression of MALAT1 was significantly elevated in various gastric cancer cell lines and gastric cancer tissues compared to normal cell lines and tissues (p < 0.01). siR-MALAT1 significantly reduced viable AGS cell numbers and induced apoptosis (p < 0.05). Deep invasion of tumor (advanced T stages) was more common in the high MALAT1-level group (p = 0.039). siR-MALAT1 significantly decreased AGS cell invasiveness and migration. siR-MALAT1 reduced expression of snail and N-cadherin, and elevated E-cadherin. The Wnt/β-catenin related genes were significantly decreased by transfection of siRNA MALAT1. MALAT1 is involved in gastric carcinogenesis via inhibition of apoptosis and promotes invasiveness via the epithelial-to-mesenchymal transition.ConclusionsIn our study, we found that deregulation of MALAT1 could be involved in both tumorigenesis and invasiveness in gastric cancer cells.
Highlights
Gastric cancer is the second leading cause of cancer globally, and the mechanism of its pathogenesis is still largely unknown
Long non-coding RNA metastasis associated lung adenocarcinoma transcript-1 (MALAT1) is significantly upregulated in gastric cancer We analyzed the microarray results of the levels of 192 “other non-coding RNAs” to find previously annotated Long non-coding RNAs (lncRNAs) with differential expressional patterns between paired cancer and adjacent normal gastric tissues
Altered expression of MALAT1 in gastric cancer cell lines and gastric cancer tissues The level of MALAT1 was measured in 19 gastric cancer cell lines and compared to normal epithelial gastric GES-1, 5 normal gastric tissues adjacent to cancer and rat normal gastric surface mucous cell (RGM-1) (Fig. 1b)
Summary
Gastric cancer is the second leading cause of cancer globally, and the mechanism of its pathogenesis is still largely unknown. Non-coding RNAs have been recognized to promote metastasis in various cancers, including gastric cancer. Gastric cancer is one of the major causes of death worldwide; the mechanism of development and progression of gastric cancer is largely unknown [1, 2]. Recent studies have revealed that non-coding RNAs such as microRNAs regulate epigenetic gene expression and are dysregulated in some gastric cancers [3,4,5,6]. We previously reported that HOTAIR can regulate invasion and cell proliferation in gastric cancer [11]. In consequence of this finding, we speculated that there might be more lncRNAs involved in gastric cancer development. In consequence of this finding, we speculated that there might be more lncRNAs involved in gastric cancer development. lncRNA expression profiles of certain diseases have been identified by microarray and RNA seq [12, 13]
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