Helicobacter pylori infection related long noncoding RNA (lncRNA) AF147447 inhibits gastric cancer proliferation and invasion by targeting MUC2 and up-regulating miR-34c
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Xiaoying Zhou1,2,*, Han Chen1,2,*, Li Zhu3,*, Bo Hao1, Weifeng Zhang1, Jie Hua1, Huiyuan Gu4, Wujuan Jin1,2, Guoxin Zhang1,2
1Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
2First Clinical Medical College of Nanjing Medical University, Nanjing, China
3Department of Gastroenterology, People’s Hospital of Jingjiang, Taizhou, China
4Department of Gastroenterology, First Affiliated Hospital of Soochow University, Suzhou, China
*These authors contributed equally to this work
Guoxin Zhang, email: [email protected]
Keywords: helicobacter pylori infection, lncRNA, gastric cancer, MUC2
Received: April 27, 2016 Accepted: October 10, 2016 Published: November 07, 2016
Long non-coding RNAs (lncRNAs) were shown to play critical roles in cancer biology. We investigated whether H. pylori infection could promote gastric cancer by regulating lncRNAs expression. Differentially expressed lncRNAs between H. pylori positive and negative tissues were identified by microarray and validated by qRT-PCR. Our results indicated that H. pylori positive tissues have a specific profile of lncRNAs. Cell biological assays with siRNA-mediated knockdown or lentivirus vector-mediated over-expression were performed to probe the functional relevance of the lncRNAs. We identified an lncRNA-AF147447 decreased expressed by H. pylori infection, which can inhibit GC proliferation and invasion in vitro and in vivo, act as a tumor suppressor in the development of H. pylori induced GC. LncRNA AF147447 could repress MUC2 expression by direct binding or increasing miR-34c expression. We also found that transcription factor E2F1 could be recruited to lncRNA AF147447 promoter by RNA immunoprecipatation and RNA pull down assays. These findings support a role of lncRNA AF147447 in tumor suppression. This discovery contributes to a better understanding of the importance of the deregulated lncRNAs by H. pylori infection and provides a rationale for the potential development of lncRNA-based targeted approaches for the treatment of H. pylori-related gastric cancer.
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