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Oncofetal H19 RNA promotes tumor metastasis

Matouk, Imad J. ; Raveh, Eli ; Abu-lail, Rasha ; Mezan, Shaul ; Gilon, Michal ; Gershtain, Eitan ; Birman, Tatiana ; Gallula, Jennifer ; Schneider, Tamar ; Barkali, Moshe ; Richler, Carmelit ; Fellig, Yakov ; Sorin, Vladimir ; Hubert, Ayala ; Hochberg, Abraham ; Czerniak, Abraham

Biochimica et biophysica acta, 2014-07, Vol.1843 (7), p.1414-1426 [Periódico revisado por pares]

Netherlands: Elsevier B.V

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Título:
Oncofetal H19 RNA promotes tumor metastasis
Autor: Matouk, Imad J. ; Raveh, Eli ; Abu-lail, Rasha ; Mezan, Shaul ; Gilon, Michal ; Gershtain, Eitan ; Birman, Tatiana ; Gallula, Jennifer ; Schneider, Tamar ; Barkali, Moshe ; Richler, Carmelit ; Fellig, Yakov ; Sorin, Vladimir ; Hubert, Ayala ; Hochberg, Abraham ; Czerniak, Abraham
Assuntos: Animals ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Cadherins - genetics ; Cadherins - metabolism ; Cell Hypoxia ; Cell Line, Tumor ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm - genetics ; E-cadherin ; Epithelial to mesenchymal transition ; Epithelial-Mesenchymal Transition - genetics ; Feedback, Physiological ; Female ; Gene Expression Regulation, Neoplastic ; H19 ; Humans ; Mammary Glands, Animal - metabolism ; Mammary Glands, Animal - pathology ; Mammary Neoplasms, Experimental - genetics ; Mammary Neoplasms, Experimental - metabolism ; Mammary Neoplasms, Experimental - pathology ; Mice ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miR-675 ; Neoplasm Metastasis ; Oxygen - metabolism ; Oxygen - pharmacology ; Phosphatidylinositol 3-Kinases - genetics ; Phosphatidylinositol 3-Kinases - metabolism ; Positive loop ; Proto-Oncogene Proteins c-akt - genetics ; Proto-Oncogene Proteins c-akt - metabolism ; RNA, Long Noncoding - genetics ; RNA, Long Noncoding - metabolism ; Signal Transduction ; Slug ; Snail Family Transcription Factors ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Transforming Growth Factor beta - pharmacology
É parte de: Biochimica et biophysica acta, 2014-07, Vol.1843 (7), p.1414-1426
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
Descrição: The oncofetal H19 gene transcribes a long non-coding RNA(lncRNA) that is essential for tumor growth. Here we found that numerous established inducers of epithelial to mesenchymal transition(EMT) also induced H19/miR-675 expression. Both TGF-β and hypoxia concomitantly induced H19 and miR-675 with the induction of EMT markers. We identified the PI3K/AKT pathway mediating the inductions of Slug, H19 RNA and miR-675 in response to TGF-β treatment, while Slug induction depended on H19 RNA. In the EMT induced multidrug resistance model, H19 level was also induced. In a mouse breast cancer model, H19 expression was tightly correlated with metastatic potential. In patients, we detected high H19 expression in all common metastatic sites tested, regardless of tumor primary origin. H19 RNA suppressed the expression of E-cadherin protein. H19 up-regulated Slug expression concomitant with the suppression of E-cadherin protein through a mechanism that involved miR-675. Slug also up-regulated H19 expression and activated its promoter. Altogether, these results may support the existence of a positive feedback loop between Slug and H19/miR-675, that regulates E-cadherin expression. H19 RNA enhanced the invasive potential of cancer cells in vitro and enhanced tumor metastasis in vivo. Additionally, H19 knockdown attenuated the scattering and tumorigenic effects of HGF/SF. Our results present novel mechanistic insights into a critical role for H19 RNA in tumor progression and indicate a previously unknown link between H19/miR-675, Slug and E-cadherin in the regulation of cancer cell EMT programs. •Multiple inducers of epithelial–mesenchymal transition up-regulate H19/miR-675.•TGF-β upregulated Slug, H19 and miR-675 through PI3K/AKT pathway.•Slug upregulation by TGF-β is H19 dependent.•H19 induces Slug is miR-675 dependent and accompanied by ablation of E-cadherin.•Evidence of Slug-H19/miR-675 positive feedback loop
Editor: Netherlands: Elsevier B.V
Idioma: Inglês

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Oncofetal H19 RNA promotes tumor metastasis

Matouk, Imad J. ; Raveh, Eli ; Abu-lail, Rasha ; Mezan, Shaul ; Gilon, Michal ; Gershtain, Eitan ; Birman, Tatiana ; Gallula, Jennifer ; Schneider, Tamar ; Barkali, Moshe ; Richler, Carmelit ; Fellig, Yakov ; Sorin, Vladimir ; Hubert, Ayala ; Hochberg, Abraham ; Czerniak, Abraham

Netherlands: Elsevier B.V

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