Nc886 is induced by TGF-β and suppresses the microRNA pathway in ovarian cancer

Ji Hye Ahn; Hyun Sung Lee; Ju Seog Lee; Yeon Su Lee; Jong Lyul Park; Seon Young Kim; Jung Ah Hwang; Nawapol Kunkeaw; Sung Yun Jung; Tae Jin Kim; Kwang Soo Lee; Sung Ho Jeon; Inhan Lee; Betty H. Johnson; Jung Hye Choi; Yong Sun Lee

doi:10.1038/s41467-018-03556-7

Nc886 is induced by TGF-β and suppresses the microRNA pathway in ovarian cancer

Ji Hye Ahn, Hyun Sung Lee, Ju Seog Lee, Yeon Su Lee, Jong Lyul Park, Seon Young Kim, Jung Ah Hwang, Nawapol Kunkeaw, Sung Yun Jung, Tae Jin Kim, Kwang Soo Lee, Sung Ho Jeon, Inhan Lee, Betty H. Johnson, Jung Hye Choi, Yong Sun Lee

Systems Biology

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

52 Scopus citations

Abstract

Transforming growth factor-β (TGF-β) signaling and microRNAs (miRNAs) are important gene regulatory components in cancer. Usually in advanced malignant stages, TGF-β signaling is elevated but global miRNA expression is suppressed. Such a gene expression signature is well illustrated in a fibrosis (or mesenchymal) subtype of ovarian cancer (OC) that is of poor prognosis. However, the interplay between the two pathways in the OC subtype has not yet been elucidated. nc886 is a recently identified non-coding RNA implicated in several malignancies. The high expression of nc886 is associated with poor prognosis in 285 OC patients. Herein, we find that in OC nc886 expression is induced by TGF-β and that nc886 binds to Dicer to inhibit miRNA maturation. By preventing the miRNA pathway, nc886 emulates TGF-β in gene expression patterns and potentiates cell adhesion, migration, invasion, and drug resistance. Here we report nc886 to be a molecular link between the TGF-β and miRNA pathways.

Original language	English (US)
Article number	1166
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-03556-7
State	Published - Dec 1 2018

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

Access to Document

10.1038/s41467-018-03556-7

Cite this

Ahn, J. H., Lee, H. S., Lee, J. S., Lee, Y. S., Park, J. L., Kim, S. Y., Hwang, J. A., Kunkeaw, N., Jung, S. Y., Kim, T. J., Lee, K. S., Jeon, S. H., Lee, I., Johnson, B. H., Choi, J. H., & Lee, Y. S. (2018). Nc886 is induced by TGF-β and suppresses the microRNA pathway in ovarian cancer. Nature communications, 9(1), Article 1166. https://doi.org/10.1038/s41467-018-03556-7

@article{f14cd77e1e444e9089ebb94d2ef005a1,

title = "Nc886 is induced by TGF-β and suppresses the microRNA pathway in ovarian cancer",

abstract = "Transforming growth factor-β (TGF-β) signaling and microRNAs (miRNAs) are important gene regulatory components in cancer. Usually in advanced malignant stages, TGF-β signaling is elevated but global miRNA expression is suppressed. Such a gene expression signature is well illustrated in a fibrosis (or mesenchymal) subtype of ovarian cancer (OC) that is of poor prognosis. However, the interplay between the two pathways in the OC subtype has not yet been elucidated. nc886 is a recently identified non-coding RNA implicated in several malignancies. The high expression of nc886 is associated with poor prognosis in 285 OC patients. Herein, we find that in OC nc886 expression is induced by TGF-β and that nc886 binds to Dicer to inhibit miRNA maturation. By preventing the miRNA pathway, nc886 emulates TGF-β in gene expression patterns and potentiates cell adhesion, migration, invasion, and drug resistance. Here we report nc886 to be a molecular link between the TGF-β and miRNA pathways.",

author = "Ahn, {Ji Hye} and Lee, {Hyun Sung} and Lee, {Ju Seog} and Lee, {Yeon Su} and Park, {Jong Lyul} and Kim, {Seon Young} and Hwang, {Jung Ah} and Nawapol Kunkeaw and Jung, {Sung Yun} and Kim, {Tae Jin} and Lee, {Kwang Soo} and Jeon, {Sung Ho} and Inhan Lee and Johnson, {Betty H.} and Choi, {Jung Hye} and Lee, {Yong Sun}",

note = "Funding Information: We thank Drs. Anil K. Sood, Nelly Auersperg, Ie-Ming Shih, and Kenneth S. Korach for OC lines (see Supplementary Table 1 for details), Dr. Narry V. Kim for Dicer reagents (antibody and plasmids), Dr. Fran{\c c}ois Fuks for the DNMT1-expressing plasmid, and Dr. Seok Hee Park for helpful discussions. This work was supported by the National Research Foundation of Korea (NRF) grants (NRF-2016R1A2B4008476 and NRF-2017R1A5A2014768) to J.-H.C.; in part by grants from the National Cancer Center, Korea (NCC-1810071-1), the NRF (NRF-2017M3A9G7073033), and the American Cancer Society (a Research Scholar Grant, RSG-12-187-01 – RMC) to Y.S.L. Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41467-018-03556-7",

language = "English (US)",

volume = "9",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Nc886 is induced by TGF-β and suppresses the microRNA pathway in ovarian cancer

AU - Ahn, Ji Hye

AU - Lee, Hyun Sung

AU - Lee, Ju Seog

AU - Lee, Yeon Su

AU - Park, Jong Lyul

AU - Kim, Seon Young

AU - Hwang, Jung Ah

AU - Kunkeaw, Nawapol

AU - Jung, Sung Yun

AU - Kim, Tae Jin

AU - Lee, Kwang Soo

AU - Jeon, Sung Ho

AU - Lee, Inhan

AU - Johnson, Betty H.

AU - Choi, Jung Hye

AU - Lee, Yong Sun

N1 - Funding Information: We thank Drs. Anil K. Sood, Nelly Auersperg, Ie-Ming Shih, and Kenneth S. Korach for OC lines (see Supplementary Table 1 for details), Dr. Narry V. Kim for Dicer reagents (antibody and plasmids), Dr. François Fuks for the DNMT1-expressing plasmid, and Dr. Seok Hee Park for helpful discussions. This work was supported by the National Research Foundation of Korea (NRF) grants (NRF-2016R1A2B4008476 and NRF-2017R1A5A2014768) to J.-H.C.; in part by grants from the National Cancer Center, Korea (NCC-1810071-1), the NRF (NRF-2017M3A9G7073033), and the American Cancer Society (a Research Scholar Grant, RSG-12-187-01 – RMC) to Y.S.L. Publisher Copyright: © 2018 The Author(s).

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Transforming growth factor-β (TGF-β) signaling and microRNAs (miRNAs) are important gene regulatory components in cancer. Usually in advanced malignant stages, TGF-β signaling is elevated but global miRNA expression is suppressed. Such a gene expression signature is well illustrated in a fibrosis (or mesenchymal) subtype of ovarian cancer (OC) that is of poor prognosis. However, the interplay between the two pathways in the OC subtype has not yet been elucidated. nc886 is a recently identified non-coding RNA implicated in several malignancies. The high expression of nc886 is associated with poor prognosis in 285 OC patients. Herein, we find that in OC nc886 expression is induced by TGF-β and that nc886 binds to Dicer to inhibit miRNA maturation. By preventing the miRNA pathway, nc886 emulates TGF-β in gene expression patterns and potentiates cell adhesion, migration, invasion, and drug resistance. Here we report nc886 to be a molecular link between the TGF-β and miRNA pathways.

AB - Transforming growth factor-β (TGF-β) signaling and microRNAs (miRNAs) are important gene regulatory components in cancer. Usually in advanced malignant stages, TGF-β signaling is elevated but global miRNA expression is suppressed. Such a gene expression signature is well illustrated in a fibrosis (or mesenchymal) subtype of ovarian cancer (OC) that is of poor prognosis. However, the interplay between the two pathways in the OC subtype has not yet been elucidated. nc886 is a recently identified non-coding RNA implicated in several malignancies. The high expression of nc886 is associated with poor prognosis in 285 OC patients. Herein, we find that in OC nc886 expression is induced by TGF-β and that nc886 binds to Dicer to inhibit miRNA maturation. By preventing the miRNA pathway, nc886 emulates TGF-β in gene expression patterns and potentiates cell adhesion, migration, invasion, and drug resistance. Here we report nc886 to be a molecular link between the TGF-β and miRNA pathways.

UR - http://www.scopus.com/inward/record.url?scp=85044445403&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044445403&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-03556-7

DO - 10.1038/s41467-018-03556-7

M3 - Article

C2 - 29563500

AN - SCOPUS:85044445403

SN - 2041-1723

VL - 9

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 1166

ER -

Nc886 is induced by TGF-β and suppresses the microRNA pathway in ovarian cancer

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this