H19 Noncoding RNA, an Independent Prognostic Factor, Regulates
Essential Rb-E2F and CDK8-beta-Catenin Signaling in Colorectal
Cancer

J 2016

H19 Noncoding RNA, an Independent Prognostic Factor, Regulates Essential Rb-E2F and CDK8-beta-Catenin Signaling in Colorectal Cancer

OHTSUKA, Masahisa; Hui LING; Cristina IVAN; Martin PICHLER; Daisuke MATSUSHITA et al.

Základní údaje

Originální název

H19 Noncoding RNA, an Independent Prognostic Factor, Regulates Essential Rb-E2F and CDK8-beta-Catenin Signaling in Colorectal Cancer

Autoři

Vydání

EBioMedicine, Amsterdam, Elsevier Science BV, 2016, 2352-3964

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/16:00093867

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

H19; RB1; E2F; CDK8; beta-Catenin; Colorectal cancer

Štítky

rivok

Změněno: 10. 3. 2017 09:28, Mgr. Eva Špillingová

Anotace

V originále

The clinical significance of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) remains largely unexplored. Here, we analyzed a large panel of lncRNA candidates with The Cancer Genome Atlas (TCGA) CRC dataset, and identified H19 as the most significant lncRNA associated with CRC patient survival. We further validated such association in two independent CRC cohorts. H19 silencing blocked G1-S transition, reduced cell proliferation, and inhibited cell migration. We profiled gene expression changes to gain mechanism insight of H19 function. Transcriptome data analysis revealed not only previously identified mechanisms such as Let-7 regulation by H19, but also RB1-E2F1 function and beta-catenin activity as essential upstream regulators mediating H19 function. Our experimental data showed that H19 affects phosphorylation of RB1 protein by regulating gene expression of CDK4 and CCND1. We further demonstrated that reduced CDK8 expression underlies changes of beta-catenin activity, and identified that H19 interacts with macroH2A, an essential regulator of CDK8 gene transcription. However, the relevance of H19-macroH2A interaction in CDK8 regulation remains to be experimentally determined. We further explored the clinical relevance of above mechanisms in clinical samples, and showed that combined analysis of H19 with its targets improved prognostic value of H19 in CRC. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Návaznosti

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

Citovat

OHTSUKA, Masahisa; Hui LING; Cristina IVAN; Martin PICHLER; Daisuke MATSUSHITA; Matthew GOBLIRSCH; Verena STIEGELBAUER; Kunitoshi SHIGEYASU; Xinna ZHANG; Meng CHEN; Fnu VIDHU; Geoffrey A. BARTHOLOMEUSZ; Yuji TOIYAMA; Masato KUSUNOKI; Yuichiro DOKI; Masaki MORI; Shumei SONG; Jillian R. GUNTHER; Sunil KRISHNAN; Ondřej SLABÝ; Ajay GOEL; Jaffer A. AJANI; Milan RADOVICH a George A. CALIN. H19 Noncoding RNA, an Independent Prognostic Factor, Regulates Essential Rb-E2F and CDK8-beta-Catenin Signaling in Colorectal Cancer. EBioMedicine. Amsterdam: Elsevier Science BV, 2016, roč. 13, November, s. 113-124. ISSN 2352-3964. Dostupné z: https://doi.org/10.1016/j.ebiom.2016.10.026.

@article{1375138,
   author = {Ohtsuka, Masahisa and Ling, Hui and Ivan, Cristina and Pichler, Martin and Matsushita, Daisuke and Goblirsch, Matthew and Stiegelbauer, Verena and Shigeyasu, Kunitoshi and Zhang, Xinna and Chen, Meng and Vidhu, Fnu and Bartholomeusz, Geoffrey A. and Toiyama, Yuji and Kusunoki, Masato and Doki, Yuichiro and Mori, Masaki and Song, Shumei and Gunther, Jillian R. and Krishnan, Sunil and Slabý, Ondřej and Goel, Ajay and Ajani, Jaffer A. and Radovich, Milan and Calin, George A.},
   article_location = {Amsterdam},
   article_number = {November},
   doi = {https://doi.org/10.1016/j.ebiom.2016.10.026},
   keywords = {H19; RB1; E2F; CDK8; beta-Catenin; Colorectal cancer},
   language = {eng},
   issn = {2352-3964},
   journal = {EBioMedicine},
   title = {H19 Noncoding RNA, an Independent Prognostic Factor, Regulates Essential Rb-E2F and CDK8-beta-Catenin Signaling in Colorectal Cancer},
   url = {http://www.sciencedirect.com/science/article/pii/S235239641630487X},
   volume = {13},
   year = {2016}
}

TY  - JOUR
ID  - 1375138
AU  - Ohtsuka, Masahisa - Ling, Hui - Ivan, Cristina - Pichler, Martin - Matsushita, Daisuke - Goblirsch, Matthew - Stiegelbauer, Verena - Shigeyasu, Kunitoshi - Zhang, Xinna - Chen, Meng - Vidhu, Fnu - Bartholomeusz, Geoffrey A. - Toiyama, Yuji - Kusunoki, Masato - Doki, Yuichiro - Mori, Masaki - Song, Shumei - Gunther, Jillian R. - Krishnan, Sunil - Slabý, Ondřej - Goel, Ajay - Ajani, Jaffer A. - Radovich, Milan - Calin, George A.
PY  - 2016
TI  - H19 Noncoding RNA, an Independent Prognostic Factor, Regulates Essential Rb-E2F and CDK8-beta-Catenin Signaling in Colorectal Cancer
JF  - EBioMedicine
VL  - 13
IS  - November
SP  - 113-124
EP  - 113-124
PB  - Elsevier Science BV
SN  - 23523964
KW  - H19
KW  - RB1
KW  - E2F
KW  - CDK8
KW  - beta-Catenin
KW  - Colorectal cancer
UR  - http://www.sciencedirect.com/science/article/pii/S235239641630487X
L2  - http://www.sciencedirect.com/science/article/pii/S235239641630487X
N2  - The clinical significance of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) remains largely unexplored. Here, we analyzed a large panel of lncRNA candidates with The Cancer Genome Atlas (TCGA) CRC dataset, and identified H19 as the most significant lncRNA associated with CRC patient survival. We further validated such association in two independent CRC cohorts. H19 silencing blocked G1-S transition, reduced cell proliferation, and inhibited cell migration. We profiled gene expression changes to gain mechanism insight of H19 function. Transcriptome data analysis revealed not only previously identified mechanisms such as Let-7 regulation by H19, but also RB1-E2F1 function and beta-catenin activity as essential upstream regulators mediating H19 function. Our experimental data showed that H19 affects phosphorylation of RB1 protein by regulating gene expression of CDK4 and CCND1. We further demonstrated that reduced CDK8 expression underlies changes of beta-catenin activity, and identified that H19 interacts with macroH2A, an essential regulator of CDK8 gene transcription. However, the relevance of H19-macroH2A interaction in CDK8 regulation remains to be experimentally determined. We further explored the clinical relevance of above mechanisms in clinical samples, and showed that combined analysis of H19 with its targets improved prognostic value of H19 in CRC. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
ER  -

OHTSUKA, Masahisa; Hui LING; Cristina IVAN; Martin PICHLER; Daisuke MATSUSHITA; Matthew GOBLIRSCH; Verena STIEGELBAUER; Kunitoshi SHIGEYASU; Xinna ZHANG; Meng CHEN; Fnu VIDHU; Geoffrey A. BARTHOLOMEUSZ; Yuji TOIYAMA; Masato KUSUNOKI; Yuichiro DOKI; Masaki MORI; Shumei SONG; Jillian R. GUNTHER; Sunil KRISHNAN; Ondřej SLABÝ; Ajay GOEL; Jaffer A. AJANI; Milan RADOVICH a George A. CALIN. H19 Noncoding RNA, an Independent Prognostic Factor, Regulates Essential Rb-E2F and CDK8-beta-Catenin Signaling in Colorectal Cancer. \textit{EBioMedicine}. Amsterdam: Elsevier Science BV, 2016, roč.~13, November, s.~113-124. ISSN~2352-3964. Dostupné z: https://doi.org/10.1016/j.ebiom.2016.10.026.

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