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.

Basic information

Original name

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

Authors

OHTSUKA, Masahisa (840 United States of America), Hui LING (840 United States of America), Cristina IVAN (840 United States of America), Martin PICHLER (840 United States of America), Daisuke MATSUSHITA (840 United States of America), Matthew GOBLIRSCH (840 United States of America), Verena STIEGELBAUER (40 Austria), Kunitoshi SHIGEYASU (840 United States of America), Xinna ZHANG (840 United States of America), Meng CHEN (840 United States of America), Fnu VIDHU (840 United States of America), Geoffrey A. BARTHOLOMEUSZ (840 United States of America), Yuji TOIYAMA (392 Japan), Masato KUSUNOKI (392 Japan), Yuichiro DOKI (392 Japan), Masaki MORI (392 Japan), Shumei SONG (840 United States of America), Jillian R. GUNTHER (840 United States of America), Sunil KRISHNAN (840 United States of America), Ondřej SLABÝ (203 Czech Republic, guarantor, belonging to the institution), Ajay GOEL (840 United States of America), Jaffer A. AJANI (840 United States of America), Milan RADOVICH (840 United States of America) and George A. CALIN (840 United States of America)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

RIV identification code

RIV/00216224:14740/16:00093867

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1016/j.ebiom.2016.10.026

UT WoS

000390704800027

Keywords in English

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

Abstract

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/).

Links

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

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 and 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, vol. 13, November, p. 113-124. ISSN 2352-3964. Available from: https://dx.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 = {http://dx.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 and 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, vol.~13, November, p.~113-124. ISSN~2352-3964. Available from: https://dx.doi.org/10.1016/j.ebiom.2016.10.026.

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