Cross-analysis of gene and miRNA genome-wide expression profiles in human fibroblasts at different stages of transformation

Paola Ostano, Silvia Bione, Cristina Belgiovine, Ilaria Chiodi, Chiara Ghimenti, A. Ivana Scovassi, Giovanna Chiorino, Chiara Mondello

Research output: Contribution to journalArticle

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Abstract

We have developed a cellular system constituted of human telomerase immortalized fibroblasts that gradually underwent neoplastic transformation during propagation in culture. We exploited this cellular system to investigate gene and miRNA transcriptional programs in cells at different stages of propagation, representing five different phases along the road to transformation, from non-transformed cells up to tumorigenic and metastatic ones. Here we show that gene and miRNA expression profiles were both able to divide cells according to their transformation phase. We identified more than 1,700 genes whose expression was highly modulated in cells at at least one propagation stage and we found that the number of modulated genes progressively increased at successive stages of transformation. These genes identified processes significantly deregulated in tumorigenic cells, such as cell differentiation, cell movement and extracellular matrix remodeling, cell cycle and apoptosis, together with upregulation of several cancer testis antigens. Alterations in cell cycle, apoptosis, and cancer testis antigen expression were particular hallmarks of metastatic cells. A parallel deregulation of a panel of 43 miRNAs strictly connected to the p53 and c-Myc pathways and with oncogenic/oncosuppressive functions was also found. Our results indicate that cen3tel cells can be a useful model for human fibroblast neoplastic transformation, which appears characterized by complex and peculiar alterations involving both genetic and epigenetic reprogramming, whose elucidation could provide useful insights into regulatory networks underlying cancerogenesis.

Original languageEnglish
Pages (from-to)24-36
Number of pages13
JournalOMICS A Journal of Integrative Biology
Volume16
Issue number1-2
DOIs
Publication statusPublished - Jan 1 2012

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Fibroblasts
MicroRNAs
Genes
Genome
Cells
Apoptosis
Antigens
Testicular Neoplasms
Deregulation
Telomerase
Gene expression
Cell Cycle
Transcriptome
Epigenomics
Cell Movement
Extracellular Matrix
Cell Differentiation
Up-Regulation
Gene Expression

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Genetics
  • Molecular Biology
  • Molecular Medicine

Cite this

Cross-analysis of gene and miRNA genome-wide expression profiles in human fibroblasts at different stages of transformation. / Ostano, Paola; Bione, Silvia; Belgiovine, Cristina; Chiodi, Ilaria; Ghimenti, Chiara; Scovassi, A. Ivana; Chiorino, Giovanna; Mondello, Chiara.

In: OMICS A Journal of Integrative Biology, Vol. 16, No. 1-2, 01.01.2012, p. 24-36.

Research output: Contribution to journalArticle

Ostano, Paola ; Bione, Silvia ; Belgiovine, Cristina ; Chiodi, Ilaria ; Ghimenti, Chiara ; Scovassi, A. Ivana ; Chiorino, Giovanna ; Mondello, Chiara. / Cross-analysis of gene and miRNA genome-wide expression profiles in human fibroblasts at different stages of transformation. In: OMICS A Journal of Integrative Biology. 2012 ; Vol. 16, No. 1-2. pp. 24-36.
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