Helicobacter pylori infection related long noncoding RNA (lncRNA) AF147447 inhibits gastric cancer proliferation and invasion by targeting MUC2 and up-regulating miR-34c.
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.
Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.|First Clinical Medical College of Nanjing Medical University, Nanjing, China.
Xiaoying
X
Zhou
Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.|First Clinical Medical College of Nanjing Medical University, Nanjing, China.
Han
H
Chen
Department of Gastroenterology, People's Hospital of Jingjiang, Taizhou, China.
Li
L
Zhu
Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Bo
B
Hao
Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Weifeng
W
Zhang
Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Jie
J
Hua
Department of Gastroenterology, First Affiliated Hospital of Soochow University, Suzhou, China.
Huiyuan
H
Gu
Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.|First Clinical Medical College of Nanjing Medical University, Nanjing, China.
Wujuan
W
Jin
Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.|First Clinical Medical College of Nanjing Medical University, Nanjing, China.
Guoxin
G
Zhang
D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D055262:Mucin-2 / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C522425:MIRN34 microRNA, human; C524625:MUC2 protein, human; D035683:MicroRNAs; D055262:Mucin-2; D062085:RNA, Long Noncoding
MUC2; gastric cancer; helicobacter pylori infection; lncRNA