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Pre-micro RNA signatures delineate stages of endothelial cell transformation in Kaposi sarcoma.

O'Hara AJ, Chugh P, Wang L, Netto EM, Luz E, Harrington WJ, Dezube BJ, Damania B, Dittmer DP - PLoS Pathog. (2009)

Bottom Line: Loss of mir-221 and gain of mir-15 expression demarked the transition from merely immortalized to fully tumorigenic endothelial cells.Mir-140 and Kaposi sarcoma-associated herpesvirus viral miRNAs increased linearly with the degree of transformation.Mir-24 emerged as a biomarker specific for KS.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

ABSTRACT
MicroRNAs (miRNA) have emerged as key regulators of cell lineage differentiation and cancer. We used precursor miRNA profiling by a novel real-time QPCR method (i) to define progressive stages of endothelial cell transformation cumulating in Kaposi sarcoma (KS) and (ii) to identify specific miRNAs that serve as biomarkers for tumor progression. We were able to compare primary patient biopsies to well-established culture and mouse tumor models. Loss of mir-221 and gain of mir-15 expression demarked the transition from merely immortalized to fully tumorigenic endothelial cells. Mir-140 and Kaposi sarcoma-associated herpesvirus viral miRNAs increased linearly with the degree of transformation. Mir-24 emerged as a biomarker specific for KS.

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Model of KSHV-dependent progressive transformation of endothelial cells as identified by pre-miRNA clustering.Upon KSHV infection, KSHV miRNAs and cellular miRNAs are induced. Through various stages of transformation, additional cellular miRNAs are induced and KSHV miRNA expression increases. E indicates primary endothelial cells. EK indicates endothelial cells, which can grow in reduced serum due to KSHV infection. ET indicates KSHV infected endothelial cells, which can form tumors in nude mice, such as E1 and L1 TIVE cells. KS indicates Kaposi sarcoma, which is the only cell type to experience notable levels of lytic reactivation with KSHV infection.
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ppat-1000389-g004: Model of KSHV-dependent progressive transformation of endothelial cells as identified by pre-miRNA clustering.Upon KSHV infection, KSHV miRNAs and cellular miRNAs are induced. Through various stages of transformation, additional cellular miRNAs are induced and KSHV miRNA expression increases. E indicates primary endothelial cells. EK indicates endothelial cells, which can grow in reduced serum due to KSHV infection. ET indicates KSHV infected endothelial cells, which can form tumors in nude mice, such as E1 and L1 TIVE cells. KS indicates Kaposi sarcoma, which is the only cell type to experience notable levels of lytic reactivation with KSHV infection.

Mentions: The mir-221 pre-miRNA emerged as a biomarker for the transition from immortalized to tumorigenic endothelial cells independent of KSHV infection status (Figure 4A). Mir-222 was co-regulated with mir-221, but did not change as dramatically (data not shown). Since mir-221/222 exhibit tumor suppressor activity in endothelial and other cancer models [55],[56],[65],[66], this suggests that the down-regulation of the mir-221 biomarker is of biological significance.


Pre-micro RNA signatures delineate stages of endothelial cell transformation in Kaposi sarcoma.

O'Hara AJ, Chugh P, Wang L, Netto EM, Luz E, Harrington WJ, Dezube BJ, Damania B, Dittmer DP - PLoS Pathog. (2009)

Model of KSHV-dependent progressive transformation of endothelial cells as identified by pre-miRNA clustering.Upon KSHV infection, KSHV miRNAs and cellular miRNAs are induced. Through various stages of transformation, additional cellular miRNAs are induced and KSHV miRNA expression increases. E indicates primary endothelial cells. EK indicates endothelial cells, which can grow in reduced serum due to KSHV infection. ET indicates KSHV infected endothelial cells, which can form tumors in nude mice, such as E1 and L1 TIVE cells. KS indicates Kaposi sarcoma, which is the only cell type to experience notable levels of lytic reactivation with KSHV infection.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2663814&req=5

ppat-1000389-g004: Model of KSHV-dependent progressive transformation of endothelial cells as identified by pre-miRNA clustering.Upon KSHV infection, KSHV miRNAs and cellular miRNAs are induced. Through various stages of transformation, additional cellular miRNAs are induced and KSHV miRNA expression increases. E indicates primary endothelial cells. EK indicates endothelial cells, which can grow in reduced serum due to KSHV infection. ET indicates KSHV infected endothelial cells, which can form tumors in nude mice, such as E1 and L1 TIVE cells. KS indicates Kaposi sarcoma, which is the only cell type to experience notable levels of lytic reactivation with KSHV infection.
Mentions: The mir-221 pre-miRNA emerged as a biomarker for the transition from immortalized to tumorigenic endothelial cells independent of KSHV infection status (Figure 4A). Mir-222 was co-regulated with mir-221, but did not change as dramatically (data not shown). Since mir-221/222 exhibit tumor suppressor activity in endothelial and other cancer models [55],[56],[65],[66], this suggests that the down-regulation of the mir-221 biomarker is of biological significance.

Bottom Line: Loss of mir-221 and gain of mir-15 expression demarked the transition from merely immortalized to fully tumorigenic endothelial cells.Mir-140 and Kaposi sarcoma-associated herpesvirus viral miRNAs increased linearly with the degree of transformation.Mir-24 emerged as a biomarker specific for KS.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

ABSTRACT
MicroRNAs (miRNA) have emerged as key regulators of cell lineage differentiation and cancer. We used precursor miRNA profiling by a novel real-time QPCR method (i) to define progressive stages of endothelial cell transformation cumulating in Kaposi sarcoma (KS) and (ii) to identify specific miRNAs that serve as biomarkers for tumor progression. We were able to compare primary patient biopsies to well-established culture and mouse tumor models. Loss of mir-221 and gain of mir-15 expression demarked the transition from merely immortalized to fully tumorigenic endothelial cells. Mir-140 and Kaposi sarcoma-associated herpesvirus viral miRNAs increased linearly with the degree of transformation. Mir-24 emerged as a biomarker specific for KS.

Show MeSH
Related in: MedlinePlus