Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MiRNA expression profiling in squamous cell carcinoma (SCC)

ABSTRACT: Despite its prevalence, the molecular basis of squamous cell carcinoma (SCC) remains poorly understood. We recently identified the developmental transcription factor Grhl3 as a potent tumor suppressor of SCC, and demonstrated that targeting of Grhl3 by a miR-21-dependent proto-oncogenic network underpins SCC in humans. Reduced levels of GRHL3 and its target gene PTEN are evident in human skin, and head and neck SCC, associated with increased expression of miR-21, which targets both tumor suppressors. Our data defines the miR-21-GRHL3-PTEN-axis as a critical tumor suppressor pathway in SCC. Total RNA was isolated from two SCC primary tissue samples and their matched normal skin controls.

ORGANISM(S): Homo sapiens

SUBMITTER: Charbel Darido

PROVIDER: E-GEOD-32868 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Targeting of the tumor suppressor GRHL3 by a miR-21-dependent proto-oncogenic network results in PTEN loss and tumorigenesis.

Darido Charbel C Georgy Smitha R SR Wilanowski Tomasz T Dworkin Sebastian S Auden Alana A Zhao Quan Q Rank Gerhard G Srivastava Seema S Finlay Moira J MJ Papenfuss Anthony T AT Pandolfi Pier Paolo PP Pearson Richard B RB Jane Stephen M SM

Cancer cell 20111101 5

Despite its prevalence, the molecular basis of squamous cell carcinoma (SCC) remains poorly understood. Here, we identify the developmental transcription factor Grhl3 as a potent tumor suppressor of SCC in mice, and demonstrate that targeting of Grhl3 by a miR-21-dependent proto-oncogenic network underpins SCC in humans. Deletion of Grhl3 in adult epidermis evokes loss of expression of PTEN, a direct GRHL3 target, resulting in aggressive SCC induced by activation of PI3K/AKT/mTOR signaling. Rest ...[more]

PMID: 22094257

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Project description:Little is known about the alterations in microRNA (miRNA) expression patterns during the consecutive stages of cervical cancer development and their association with chromosomal instability and epigenetic changes. We integrated miRNA expression profiles in normal cervical squamous epithelium, high-grade precancerous lesions (CIN2-3), squamous cell carcinomas (SCC) and adenocarcinomas (AdCAs) with previously generated chromosomal profiles of the same samples. In addition, the DNA methylation status of downregulated miRNAs located in a CpG island was determined. Significantly differential expression during the consecutive stages of cervical SCC development was observed for 106 miRNAs. Altered expression of 5 significantly differentially expressed miRNAs, hsa-miR-9 (1q23.2), hsa-miR-15b (3q25.32), hsa-miR-28-5p (3q27.3), hsa-miR-100 and hsa-miR-125b (both 11q24.1) was directly linked to frequent chromosomal alterations. Another 9 significantly downregulated miRNAs were located within a CpG island. Three of these 9 miRNAs, hsa-miR-203, hsa-miR-572, and hsa-miR-638, showed increased methylation in cervical cancer cell lines and HPV-immortalised cells compared to primary keratinocytes. Functional analyses were performed for hsa-miR-9, representing a potential oncogene with increased expression linked to a chromosomal gain, and hsa-miR-203, representing a potential tumour suppressor gene silenced by DNA methylation. Hsa-miR-9 and hsa-miR-203 were found to alter cell viability and anchorage independent growth in vitro, respectively, supporting their oncogenic and tumour suppressive function in cervical cancer. In conclusion, differential expression of 106 miRNAs, partly associated with chromosomal alterations and epigenetic changes, was observed during cervical SCC development. Altered expression of hsa-miR-9 and hsa-miR-203 was shown to be functionally relevant, underlining the importance of deregulated miRNA expression in cervical carcinogenesis. 10 squamous cell carcinomas of the cervix, 9 adenocarcinomas of the cervix, 18 high-grade cervical intraepithelial neoplasias (CIN2-3), and 10 cervical squamous epithelial samples with normal histology were analysed using single channel (Cy3) miRNA microarrays from Agilent (G4471A-016436).

Dataset Information

MiRNA expression profiling in squamous cell carcinoma (SCC)

Publications

Targeting of the tumor suppressor GRHL3 by a miR-21-dependent proto-oncogenic network results in PTEN loss and tumorigenesis.

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