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Global microRNA profiles in cervical squamous cell carcinoma depend on Drosha expression levels
The Journal of pathology, 2007-08, Vol.212 (4), p.368-377
Muralidhar, B
Goldstein, LD
Ng, G
Winder, DM
Palmer, RD
Gooding, EL
Barbosa-Morais, NL
Mukherjee, G
Thorne, NP
Roberts, I
Pett, MR
Coleman, N
2007
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Muralidhar, B
Goldstein, LD
Ng, G
Winder, DM
Palmer, RD
Gooding, EL
Barbosa-Morais, NL
Mukherjee, G
Thorne, NP
Roberts, I
Pett, MR
Coleman, N
Titel
Global microRNA profiles in cervical squamous cell carcinoma depend on Drosha expression levels
Ist Teil von
The Journal of pathology, 2007-08, Vol.212 (4), p.368-377
Ort / Verlag
Chichester, UK: John Wiley & Sons, Ltd
Erscheinungsjahr
2007
Quelle
Wiley-Blackwell Journals
Beschreibungen/Notizen
Gain of chromosome 5p is seen in over 50% of advanced cervical squamous cell carcinomas (SCCs), although the genes responsible for the selective advantage provided by this abnormality are poorly understood. In the W12 cervical carcinogenesis model, we observed that 5p gain was rapidly selected over ∼15 population doublings and was associated with the acquisition of a growth advantage and invasiveness. The most significantly upregulated transcript following 5p gain was the microRNA (miRNA) processor Drosha. In clinically progressed cervical SCC, Drosha copy‐number gain was seen in 21/36 clinical samples and 8/10 cell lines and there was a significant association between Drosha transcript levels and copy‐number gain. Other genes in the miRNA processing pathway, DGCR8, XPO5 and Dicer, showed infrequent copy‐number gain and over‐expression. Drosha copy‐number and expression were not elevated in pre‐malignant cervical squamous intraepithelial lesions. Importantly, global miRNA profiling showed that Drosha over‐expression in cervical SCC appears to be of functional significance. Unsupervised principal component analysis of a mixed panel of cervical SCC cell lines and clinical specimens showed clear separation according to Drosha over‐expression. miRNAs most significantly associated with Drosha over‐expression are implicated in carcinogenesis in other tissues, suggesting that they regulate fundamental processes in neoplastic progression. Our evidence suggests that copy‐number driven over‐expression of Drosha and consequent changes in miRNAs are likely to be important contributors to the selective advantage provided by 5p gain in cervical neoplastic progression. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Sprache
Englisch
Identifikatoren
ISSN: 0022-3417
eISSN: 1096-9896
DOI: 10.1002/path.2179
Titel-ID: cdi_crossref_primary_10_1002_path_2179
Format
–
Schlagworte
Biological and medical sciences
,
Carcinoma, Squamous Cell - genetics
,
Carcinoma, Squamous Cell - metabolism
,
Carcinoma, Squamous Cell - pathology
,
Cells, Cultured
,
cervix
,
Chromosomes, Human, Pair 5 - genetics
,
Drosha
,
Female
,
Female genital diseases
,
Gynecology. Andrology. Obstetrics
,
Humans
,
Investigative techniques, diagnostic techniques (general aspects)
,
Medical sciences
,
microRNA
,
MicroRNAs - genetics
,
Neoplasm Invasiveness
,
Neoplasm Proteins - metabolism
,
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
,
Polymerase Chain Reaction - methods
,
Principal Component Analysis
,
progression
,
Ribonuclease III - metabolism
,
RNA, Neoplasm - genetics
,
SCC
,
Tumors
,
Uterine Cervical Neoplasms - genetics
,
Uterine Cervical Neoplasms - metabolism
,
Uterine Cervical Neoplasms - pathology
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