Quan-Jun Deng1, Li-Qun Xie2, Hua Li2. 1. Department of Gastroenterology, Affiliated Hospital, Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, China. Electronic address: quanjdeng@163.com. 2. Department of Gastroenterology, Affiliated Hospital, Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, China.
Abstract
OBJECTIVE: Long non-coding RNAs (lncRNAs) have been demonstrated to participate in various cancers. Here, the role and its potential mechanism of MALAT1 in invasion and migration of gastric cancer (GC) were investigated. METHODS: Gastric adenocarcinoma tissues and matched normal adjacent tissues were isolated from 25 patients with GC. The expression of epidermal growth factor-like domain-containing protein 7 (EGFL7) was detected in the normal gastric mucosa epithelial GES-1 cell line and three different differentiation GC cell lines, including MKN28 (well-differentiated adenocarcinoma), SGC7901 (moderately differentiated adenocarcinoma) and BGC823 (poorly differentiated adenocarcinoma). Tumor xenotransplant mouse model was established with the injection of cell line pretreated with lentiviral vectors for si-MALAT1 or si-control. RESULTS: The expression of MALAT1 was up-regulated in GC tissues and three cell lines. Si-MALAT1/pcDNA-MALAT1 induced the decrease of cell invasion and migration, while the effects were reversed by the transfection of pcDNA-EGFL7/si-EGFL7. ChIP assay showed that MALAT1 regulated EGFL7 expression by altering the level of H3 histone acetylation in EGFL7 promoter. In tumor xenotransplant mice, down-regulated MALAT1 contributed to the inhibition of tumor metastasis. CONCLUSIONS: Up-regulated MALAT1 promoted the invasion and metastasis of GC, and the increase of EGFL7 expression was a potential mechanism via altering its H3 histone acetylation level.
OBJECTIVE: Long non-coding RNAs (lncRNAs) have been demonstrated to participate in various cancers. Here, the role and its potential mechanism of MALAT1 in invasion and migration of gastric cancer (GC) were investigated. METHODS: Gastric adenocarcinoma tissues and matched normal adjacent tissues were isolated from 25 patients with GC. The expression of epidermal growth factor-like domain-containing protein 7 (EGFL7) was detected in the normal gastric mucosa epithelial GES-1 cell line and three different differentiation GC cell lines, including MKN28 (well-differentiated adenocarcinoma), SGC7901 (moderately differentiated adenocarcinoma) and BGC823 (poorly differentiated adenocarcinoma). Tumor xenotransplant mouse model was established with the injection of cell line pretreated with lentiviral vectors for si-MALAT1 or si-control. RESULTS: The expression of MALAT1 was up-regulated in GC tissues and three cell lines. Si-MALAT1/pcDNA-MALAT1 induced the decrease of cell invasion and migration, while the effects were reversed by the transfection of pcDNA-EGFL7/si-EGFL7. ChIP assay showed that MALAT1 regulated EGFL7 expression by altering the level of H3 histone acetylation in EGFL7 promoter. In tumor xenotransplant mice, down-regulated MALAT1 contributed to the inhibition of tumor metastasis. CONCLUSIONS: Up-regulated MALAT1 promoted the invasion and metastasis of GC, and the increase of EGFL7 expression was a potential mechanism via altering its H3 histone acetylation level.
Authors: Nevenka Dudvarski Stanković; Frank Bicker; Stefanie Keller; David Tw Jones; Patrick N Harter; Arne Kienzle; Clarissa Gillmann; Philipp Arnold; Anna Golebiewska; Olivier Keunen; Alf Giese; Andreas von Deimling; Tobias Bäuerle; Simone P Niclou; Michel Mittelbronn; Weilan Ye; Stefan M Pfister; Mirko H Schmidt Journal: EMBO Mol Med Date: 2018-09 Impact factor: 12.137