Document Detail


miR-23b targets proline oxidase, a novel tumor suppressor protein in renal cancer.
MedLine Citation:
PMID:  20562915     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Proline oxidase (POX) is a novel mitochondrial tumor suppressor that can suppress proliferation and induce apoptosis through the generation of reactive oxygen species (ROS) and decreasing hypoxia-inducible factor (HIF) signaling. Recent studies have shown the absence of expression of POX in human cancer tissues, including renal cancer. However, the mechanism for the loss of POX remains obscure. No genetic or epigenetic variation of POX gene was found. In this study, we identified the upregulated miR-23b in renal cancer as an important regulator of POX. Ectopic overexpression of miR-23b in normal renal cells resulted in striking downregulation of POX, whereas POX expression increased markedly when endogenous miR-23b was knocked down by its antagomirs in renal cancer cells. Consistent with the POX-mediated tumor suppression pathway, these antagomirs induced ROS, inhibited HIF signaling and increased apoptosis. Furthermore, we confirmed the regulation of miR-23b on POX and its function in the DLD1 Tet-off POX cell system. Using a luciferase reporter system, we verified the direct binding of miR-23b to the POX mRNA 3'-untranslated region. In addition, pairs of human renal carcinoma and normal tissues showed a negative correlation between miR-23b and POX protein expression, providing its clinical corroboration. Taken together, our results suggested that miR-23b, by targeting POX, could function as an oncogene; decreasing miR-23b expression may prove to be an effective way of inhibiting kidney tumor growth.
Authors:
W Liu; O Zabirnyk; H Wang; Y-H Shiao; M L Nickerson; S Khalil; L M Anderson; A O Perantoni; J M Phang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2010-06-21
Journal Detail:
Title:  Oncogene     Volume:  29     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-02     Completed Date:  2010-10-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  4914-24     Citation Subset:  IM    
Affiliation:
Laboratory of Comparative Carcinogenesis, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, USA. liuwei3@mail.nih.gov
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MeSH Terms
Descriptor/Qualifier:
3' Untranslated Regions / genetics
Base Sequence
Cell Line, Tumor
Cell Proliferation
Down-Regulation / genetics
Gene Expression Regulation, Neoplastic / genetics
Humans
Kidney Neoplasms / enzymology*,  genetics*,  pathology
MicroRNAs / genetics*
Proline Oxidase / genetics*,  metabolism
RNA, Messenger / genetics
Tumor Suppressor Proteins / genetics*,  metabolism
Chemical
Reg. No./Substance:
0/3' Untranslated Regions; 0/MIRN23 microRNA, human; 0/MicroRNAs; 0/RNA, Messenger; 0/Tumor Suppressor Proteins; EC 1.5.3.-/Proline Oxidase

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