Abstract:
BACKGROUND:Kallikrein-related peptidase 6 (KLK6), a member of the serine protease family of kallikrein (KLK) genes, is dysregulated in ovarian carcinomas (OCa) and its overexpression is associated with poor prognosis. Regulation of its expression is poorly understood and is likely to be influenced by multiple mechanisms. The KLK locus is subject to copy number changes and heterogeneity in serous OCas. These copy number imbalances generally correlate with KLK6 protein expression; however, this is not always the case. In this study we explored the role of miRNAs in the posttranscriptional control of KLK6 expression and the contributions of copy numbers, not only of the KLK locus, but also of the miRNAs predicted to regulate it. METHODS AND RESULTS:By miRNA profiling of the KLK6-overexpressing OCa cell line, OVCAR-3, we identified overexpressed and underexpressed miRNAs. Publically available miRNA databases identified the human miRNA lethal 7 (hsa-let-7) family members as putative regulating miRNAs, from which hsa-let-7a was chosen for functional analysis. The transient transfection of hsa-let-7a to OVCAR-3 resulted in a decrease of KLK6 secreted protein. Moreover, such transfection was also able to weakly affect the expression of another member of the KLK gene family, KLK10 (kallikrein-related peptidase 10). Cytogenomic analysis, including array comparative genomic hybridization, fluorescence in situ hybridization, and spectral karyotyping revealed the overall net copy number losses of hsa-let-7a and other miRNAs predicted to target KLK6. CONCLUSIONS:The hsa-let-7 family member hsa-let-7a is a modulator of KLK6 protein expression that is independent of the KLK6 copy number status.
journal_name
Clin Chemjournal_title
Clinical chemistryauthors
Bayani J,Kuzmanov U,Saraon P,Fung WA,Soosaipillai A,Squire JA,Diamandis EPdoi
10.1373/clinchem.2012.193060subject
Has Abstractpub_date
2013-01-01 00:00:00pages
296-305issue
1eissn
0009-9147issn
1530-8561pii
clinchem.2012.193060journal_volume
59pub_type
杂志文章abstract:BACKGROUND:Neuroblastoma is the most common extracranial malignant solid tumor in children under 5 years and is characterized by a wide clinical and biological heterogeneity, from spontaneously regressive forms to cancers with a rapid and fatal progression. MYCN oncogene amplification is considered the most important p...
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journal_title:Clinical chemistry
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journal_title:Clinical chemistry
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doi:
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journal_title:Clinical chemistry
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doi:
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journal_title:Clinical chemistry
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doi:
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journal_title:Clinical chemistry
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doi:
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journal_title:Clinical chemistry
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doi:
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journal_title:Clinical chemistry
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doi:
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doi:
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doi:
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journal_title:Clinical chemistry
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doi:
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