title: Long Noncoding RNA H19-Derived miR-675 Enhances Proliferation and Invasion via RUNX1 in Gastric Cancer Cells.
abstract: The lncRNA H19 and its mature product miR-675 have recently been shown to be upregulated and promote the progression of gastric cancer. However, the detailed function and underlying molecular mechanism of H19/miR-675 in the carcinogenesis of gastric cancer remains unclear. In this study, we found that H19 depended on miR-675 to enhance the proliferation and invasion of gastric cancer AGS cells, and the expression of miR-675 was positively correlated with H19 in patients with gastric cancer. Subsequently, the tumor-suppressor runt domain transcription factor 1 (RUNX1) was confirmed to be a downstream molecule of H19/miR-675 axis, since overexpression of H19 or miR-675 significantly decreased RUNX1 expression in AGS cells, and knockdown of H19 or miR-675 enhanced RUNX1 expression. More importantly, a series of assays further demonstrated that introduction of RUNX1 abrogated H19/miR-675-induced Akt/mTOR pathway activation and the following cellular proliferation and invasion of AGS cells. To our knowledge, this is the time to demonstrate that RUNX1 serves as a link between H19/miR-675 axis and Akt/mTOR signaling and is a pivotal mediator in gastric cancer progression induced by H19/miR-675. Thus, our study provides important clues for understanding the key roles of lncRNA-miRNA functional network and identifying new therapeutic targets for gastric cancer.
authors.affiliation: Department of Hepatobiliary and Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Gao
authors.initials: G
authors.lastname: Liu
authors.forename: Tian
authors.initials: T
authors.lastname: Xiang
authors.forename: Quan-Feng
authors.initials: QF
authors.lastname: Wu
authors.forename: Wei-Xing
authors.initials: WX
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D051058:Oncogene Protein v-akt / Q000235:genetics; D062085:RNA, Long Noncoding / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C094335:H19 long non-coding RNA; C548379:MIRN675 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; C493728:RUNX1 protein, human; C546842:MTOR protein, human; D051058:Oncogene Protein v-akt; D058570:TOR Serine-Threonine Kinases