MicroRNAs of miR-17-92 cluster increase gene expression by targeting mRNA-destabilization pathways

Eunsun Jung; Youngmo Seong; Bohyun Jeon; Young Soo Kwon; Hoseok Song

doi:10.1016/j.bbagrm.2018.06.003

MicroRNAs of miR-17-92 cluster increase gene expression by targeting mRNA-destabilization pathways

Eunsun Jung, Youngmo Seong, Bohyun Jeon, Young Soo Kwon, Hoseok Song

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) of the miR-17-92 cluster are overexpressed in human cancers, and their enforced expression is tumorigenic in mouse models. A number of genes are reported to be targets of these miRNAs and are implicated in their tumorigenic potential. However, the mode of action by miRNAs suggests that global analysis of their targets is required to understand their cellular roles. In this study, we globally analyzed AGO2-bound mRNAs and found that the miR-17-92 miRNAs coherently repress multiple targets involved in the destabilization of mRNA. While the miRNAs repress the expression of their targets, they increase stability and lengthen the poly-A tails of non-target mRNAs. Furthermore, the expression of BTG3, TOB1, CSNK1A1 and ANKRD52 is negatively correlated with the expression of the miR-17-92 cluster in cancer cell lines. Our results suggest that the miR-17-92 miRNAs promote tumorigenesis not only by repression of key regulators, but also by posttranscriptional increases of global gene expression.

Original language	English
Pages (from-to)	603-612
Number of pages	10
Journal	Biochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume	1861
Issue number	7
DOIs	https://doi.org/10.1016/j.bbagrm.2018.06.003
Publication status	Published - 2018 Jul

Bibliographical note

Funding Information:
This work was supported by the Ministry of Education, Science and Technology through the National Research Foundation of Korea [ NRF-2011-0024962 and NRF-2015R1D1A1A01060145 to Y.-S.K.; 2014R1A1A2058610 to H.S.], and Ministry of Health and Welfare [ HI15C2835 to H.S.].

Publisher Copyright:
© 2018 Elsevier B.V.

Keywords

CrossLinking ImmunoPrecipitation
Poly-A tail
RNA stability
miR-17-92 cluster
microRNA

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bbagrm.2018.06.003

Cite this

@article{41c3a224116645bd987abff72882fb4f,

title = "MicroRNAs of miR-17-92 cluster increase gene expression by targeting mRNA-destabilization pathways",

abstract = "MicroRNAs (miRNAs) of the miR-17-92 cluster are overexpressed in human cancers, and their enforced expression is tumorigenic in mouse models. A number of genes are reported to be targets of these miRNAs and are implicated in their tumorigenic potential. However, the mode of action by miRNAs suggests that global analysis of their targets is required to understand their cellular roles. In this study, we globally analyzed AGO2-bound mRNAs and found that the miR-17-92 miRNAs coherently repress multiple targets involved in the destabilization of mRNA. While the miRNAs repress the expression of their targets, they increase stability and lengthen the poly-A tails of non-target mRNAs. Furthermore, the expression of BTG3, TOB1, CSNK1A1 and ANKRD52 is negatively correlated with the expression of the miR-17-92 cluster in cancer cell lines. Our results suggest that the miR-17-92 miRNAs promote tumorigenesis not only by repression of key regulators, but also by posttranscriptional increases of global gene expression.",

keywords = "CrossLinking ImmunoPrecipitation, Poly-A tail, RNA stability, miR-17-92 cluster, microRNA",

author = "Eunsun Jung and Youngmo Seong and Bohyun Jeon and Kwon, {Young Soo} and Hoseok Song",

note = "Funding Information: This work was supported by the Ministry of Education, Science and Technology through the National Research Foundation of Korea [ NRF-2011-0024962 and NRF-2015R1D1A1A01060145 to Y.-S.K.; 2014R1A1A2058610 to H.S.], and Ministry of Health and Welfare [ HI15C2835 to H.S.]. Publisher Copyright: {\textcopyright} 2018 Elsevier B.V.",

year = "2018",

month = jul,

doi = "10.1016/j.bbagrm.2018.06.003",

language = "English",

volume = "1861",

pages = "603--612",

journal = "Biochimica et Biophysica Acta - Gene Regulatory Mechanisms",

issn = "1874-9399",

publisher = "Elsevier B.V.",

number = "7",

}

TY - JOUR

T1 - MicroRNAs of miR-17-92 cluster increase gene expression by targeting mRNA-destabilization pathways

AU - Jung, Eunsun

AU - Seong, Youngmo

AU - Jeon, Bohyun

AU - Kwon, Young Soo

AU - Song, Hoseok

N1 - Funding Information: This work was supported by the Ministry of Education, Science and Technology through the National Research Foundation of Korea [ NRF-2011-0024962 and NRF-2015R1D1A1A01060145 to Y.-S.K.; 2014R1A1A2058610 to H.S.], and Ministry of Health and Welfare [ HI15C2835 to H.S.]. Publisher Copyright: © 2018 Elsevier B.V.

PY - 2018/7

Y1 - 2018/7

N2 - MicroRNAs (miRNAs) of the miR-17-92 cluster are overexpressed in human cancers, and their enforced expression is tumorigenic in mouse models. A number of genes are reported to be targets of these miRNAs and are implicated in their tumorigenic potential. However, the mode of action by miRNAs suggests that global analysis of their targets is required to understand their cellular roles. In this study, we globally analyzed AGO2-bound mRNAs and found that the miR-17-92 miRNAs coherently repress multiple targets involved in the destabilization of mRNA. While the miRNAs repress the expression of their targets, they increase stability and lengthen the poly-A tails of non-target mRNAs. Furthermore, the expression of BTG3, TOB1, CSNK1A1 and ANKRD52 is negatively correlated with the expression of the miR-17-92 cluster in cancer cell lines. Our results suggest that the miR-17-92 miRNAs promote tumorigenesis not only by repression of key regulators, but also by posttranscriptional increases of global gene expression.

AB - MicroRNAs (miRNAs) of the miR-17-92 cluster are overexpressed in human cancers, and their enforced expression is tumorigenic in mouse models. A number of genes are reported to be targets of these miRNAs and are implicated in their tumorigenic potential. However, the mode of action by miRNAs suggests that global analysis of their targets is required to understand their cellular roles. In this study, we globally analyzed AGO2-bound mRNAs and found that the miR-17-92 miRNAs coherently repress multiple targets involved in the destabilization of mRNA. While the miRNAs repress the expression of their targets, they increase stability and lengthen the poly-A tails of non-target mRNAs. Furthermore, the expression of BTG3, TOB1, CSNK1A1 and ANKRD52 is negatively correlated with the expression of the miR-17-92 cluster in cancer cell lines. Our results suggest that the miR-17-92 miRNAs promote tumorigenesis not only by repression of key regulators, but also by posttranscriptional increases of global gene expression.

KW - CrossLinking ImmunoPrecipitation

KW - Poly-A tail

KW - RNA stability

KW - miR-17-92 cluster

KW - microRNA

UR - http://www.scopus.com/inward/record.url?scp=85049303284&partnerID=8YFLogxK

U2 - 10.1016/j.bbagrm.2018.06.003

DO - 10.1016/j.bbagrm.2018.06.003

M3 - Article

AN - SCOPUS:85049303284

SN - 1874-9399

VL - 1861

SP - 603

EP - 612

JO - Biochimica et Biophysica Acta - Gene Regulatory Mechanisms

JF - Biochimica et Biophysica Acta - Gene Regulatory Mechanisms

IS - 7

ER -

MicroRNAs of miR-17-92 cluster increase gene expression by targeting mRNA-destabilization pathways

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this