A suppressive role of ionizing radiation-responsive miR-29c in the development of liver carcinoma via targeting WIP1

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dc.contributor.authorWang, Bo
dc.contributor.authorLi, Dongping
dc.contributor.authorSidler, Corinne
dc.contributor.authorRodriquez-Juarez, Rocio
dc.contributor.authorSingh, Natasha
dc.contributor.authorHeyns, Mieke
dc.contributor.authorIlnytskyy, Yaroslav
dc.contributor.authorBronson, Roderick T.
dc.contributor.authorKovalchuk, Olga
dc.date.accessioned2019-01-24T20:19:44Z
dc.date.available2019-01-24T20:19:44Z
dc.date.issued2015
dc.descriptionSherpa Rome blue journal. Open access article. Creative Commons Attribution 3.0 License (CC BY 3.0) appliesen_US
dc.description.abstractHepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide, and it has been linked to radiation exposure. As a well-defined oncogene, wild-type p53-induced phosphatase 1 (WIP1) plays an inhibitory role in several tumor suppressor pathways, including p53. WIP1 is amplified and overexpressed in many malignancies, including HCC. However, the underlying mechanisms remain largely unknown. Here, we show that low-dose ionizing radiation (IR) induces miR-29c expression in female mouse liver, while inhibiting its expression in HepG2, a human hepatocellular carcinoma cell line which is used as a model system in this study. miR29c expression is downregulated in human hepatocellular carcinoma cells, which is inversely correlated with WIP1 expression. miR-29c attenuates luciferase activity of a reporter harboring the 3’UTR binding motif of WIP1 mRNA. Ectopic expression of miR-29c significantly represses cell proliferation and induces apoptosis and G1 arrest in HepG2. In contrast, the knockdown of miR-29c greatly enhances HepG2 cell proliferation and suppresses apoptosis. The biological effects of miR-29c may be mediated by its target WIP1 which regulates p53 activity via dephosphorylation at Ser-15. Finally, fluorescence in situ hybridization (FISH) and immunohistochemical analyses indicate that miR-29c is downregulated in 50.6% of liver carcinoma tissues examined, whereas WIP1 is upregulated in 45.4% of these tissues. The expression of miR-29c inversely correlates with that of WIP1 in HCC. Our results suggest that the IR-responsive miR-29c may function as a tumor suppressor that plays a crucial role in the development of liver carcinoma via targeting WIP1, therefore possibly representing a target molecule for therapeutic intervention for this disease.en_US
dc.description.peer-reviewYesen_US
dc.identifier.citationWang, B., Li, D., Sidler, C., Rodriquez-Juarez, R., Singh, N., Heyns, M.,...Kovalchuk, O. (2015). A suppressive role of ionizing radiation-responsive miR-29c in the development of liver carcinoma via targeting WIP1. Oncotarget, 6(12), 9937-9950. https://doi.org/10.18632/oncotarget.3157en_US
dc.identifier.urihttps://hdl.handle.net/10133/5277
dc.language.isoen_USen_US
dc.publisherImpact Journalsen_US
dc.publisher.departmentDepartment of Biological Sciencesen_US
dc.publisher.facultyArts and Scienceen_US
dc.publisher.institutionUniversity of Lethbridgeen_US
dc.publisher.institutionQiqihar Medical Universityen_US
dc.publisher.institutionThe Dana Farber/Harvard Comprehensive Cancer Centeren_US
dc.publisher.urlhttps://doi.org/10.18632/oncotarget.3157
dc.subjectIonizing radiationen_US
dc.subjectmiR-29cen_US
dc.subjectHepatocellular carcinomaen_US
dc.subjectWIP1en_US
dc.subject.lcshLiver--Cancer
dc.subject.lcshLiver--Cancer--Research
dc.titleA suppressive role of ionizing radiation-responsive miR-29c in the development of liver carcinoma via targeting WIP1en_US
dc.typeArticleen_US
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