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https://doi.org/10.1186/1476-4598-10-29
Title: | miR-449 inhibits cell proliferation and is down-regulated in gastric cancer | Authors: | Bou Kheir, T Futoma-Kazmierczak, E Jacobsen, A Krogh, A Bardram, L Hother, C Grønbæk, K Federspiel, B Lund, A.H Friis-Hansen, L |
Keywords: | beta galactosidase caspase 3 cyclin dependent kinase 6 cyclin E gastrin geminin histone deacetylase 1 miRNA 449 nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1 protein p21 protein p53 scatter factor receptor sirtuin 1 tumor suppressor protein unclassified drug gastrin microRNA MIRN34 microRNA, human MIRN449 microRNA, human Mirn449 microRNA, mouse protein p53 animal cell animal tissue apoptosis article cell growth cell proliferation controlled study down regulation female fluorescence activated cell sorting gene overexpression Helicobacter infection human human tissue knockout mouse microarray analysis mouse nonhuman polymerase chain reaction stomach stomach cancer stomach carcinogenesis wild type adenoma animal cell aging cell cycle down regulation gene expression regulation genetics Helicobacter infection Helicobacter pylori metabolism molecular genetics mouse mutant nucleotide sequence pathology physiology signal transduction stomach antrum stomach tumor tumor cell line Animalia Bacteria (microorganisms) Helicobacter pylori Mus Adenoma Animals Base Sequence Cell Aging Cell Cycle Cell Line, Tumor Cell Proliferation Down-Regulation Gastrins Gene Expression Regulation, Neoplastic Helicobacter Infections Helicobacter pylori Humans Mice Mice, Knockout MicroRNAs Molecular Sequence Data Pyloric Antrum Signal Transduction Stomach Neoplasms Tumor Suppressor Protein p53 |
Issue Date: | 2011 | Citation: | Bou Kheir, T, Futoma-Kazmierczak, E, Jacobsen, A, Krogh, A, Bardram, L, Hother, C, Grønbæk, K, Federspiel, B, Lund, A.H, Friis-Hansen, L (2011). miR-449 inhibits cell proliferation and is down-regulated in gastric cancer. Molecular Cancer 10 : 29. ScholarBank@NUS Repository. https://doi.org/10.1186/1476-4598-10-29 | Rights: | Attribution 4.0 International | Abstract: | Background: Gastric cancer is the fourth most common cancer in the world and the second most prevalent cause of cancer related death. The development of gastric cancer is mainly associated with H. Pylori infection leading to a focus in pathology studies on bacterial and environmental factors, and to a lesser extent on the mechanistic development of the tumour. MicroRNAs are small non-coding RNA molecules involved in post-transcriptional gene regulation. They are found to regulate genes involved in diverse biological functions and alterations in microRNA expression have been linked to the pathogenesis of many malignancies. The current study is focused on identifying microRNAs involved in gastric carcinogenesis and to explore their mechanistic relevance by characterizing their targets.Results: Invitrogen NCode miRNA microarrays identified miR-449 to be decreased in 1-year-old Gastrin KO mice and in H. Pylori infected gastric tissues compared to tissues from wild type animals. Growth rate of gastric cell lines over-expressing miR-449 was inhibited by 60% compared to controls. FACS cell cycle analysis of miR-449 over-expressing cells showed a significant increase in the sub-G 1 fraction indicative of apoptosis. ß-Gal assays indicated a senescent phenotype of gastric cell lines over-expressing miR-449. Affymetrix 133v2 arrays identified GMNN, MET, CCNE2, SIRT1 and CDK6 as miR-449 targets. Luciferase assays were used to confirm GMNN, MET, CCNE2 and SIRT1 as direct targets. We also show that miR-449 over-expression activated p53 and its downstream target p21 as well as the apoptosis markers cleaved CASP3 and PARP. Importantly, qPCR analyses showed a loss of miR-449 expression in human clinical gastric tumours compared to normal tissues.Conclusions: In this study, we document a diminished expression of miR-449 in Gastrin KO mice and further confirmed its loss in human gastric tumours. We investigated the function of miR-449 by identifying its direct targets. Furthermore we show that miR-449 induces senescence and apoptosis by activating the p53 pathway. © 2011 Kheir et al; licensee BioMed Central Ltd. | Source Title: | Molecular Cancer | URI: | https://scholarbank.nus.edu.sg/handle/10635/181639 | ISSN: | 14764598 | DOI: | 10.1186/1476-4598-10-29 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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