Novel miR-5582-5p functions as a tumor suppressor by inducing apoptosis and cell cycle arrest in cancer cells through direct targeting of GAB1, SHC1, and CDK2

Hyun Ju An; Seo Young Kwak; Je Ok Yoo; Jae Sung Kim; In Hwa Bae; Myung Jin Park; Mee Yon Cho; Joon Kim; Young Hoon Han

doi:10.1016/j.bbadis.2016.07.017

Novel miR-5582-5p functions as a tumor suppressor by inducing apoptosis and cell cycle arrest in cancer cells through direct targeting of GAB1, SHC1, and CDK2

Hyun Ju An, Seo Young Kwak, Je Ok Yoo, Jae Sung Kim, In Hwa Bae, Myung Jin Park, Mee Yon Cho, Joon Kim, Young Hoon Han

Pathology

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

17 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) play pivotal roles in tumorigenesis as either tumor suppressors or oncogenes. In the present study, we discovered and demonstrated the tumor suppressive function of a novel miRNA miR-5582-5p. miR-5582-5p induced apoptosis and cell cycle arrest in cancer cells, but not in normal cells. GAB1, SHC1, and CDK2 were identified as direct targets of miR-5582-5p. Knockdown of GAB1/SHC1 or CDK2 phenocopied the apoptotic or cell cycle arrest-inducing function of miR-5582-5p, respectively. The expression of miR-5582-5p was lower in tumor tissues than in adjacent normal tissues of colorectal cancer patients, while the expression of the target proteins exhibited patterns opposite to that of miR-5582-5p. Intratumoral injection of a miR-5582-5p mimic or induced expression of miR-5582-5p in tumor cells suppressed tumor growth in HCT116 xenografts. Collectively, our results suggest a novel tumor suppressive function for miR-5582-5p and its potential applicability for tumor control.

Original language	English
Pages (from-to)	1926-1937
Number of pages	12
Journal	Biochimica et Biophysica Acta - Molecular Basis of Disease
Volume	1862
Issue number	10
DOIs	https://doi.org/10.1016/j.bbadis.2016.07.017
Publication status	Published - 2016 Oct 1

Bibliographical note

Funding Information:
This research was supported by the National R&D Program through the Korea Institute of Radiological and Medical Sciences funded by the Ministry of Science, ICT & Future Planning, Republic of Korea ( 1711031811 , 1711031819 ) and in part by a grant to J. Kim from the National Research Foundation of Korea ( NRF2015R1A2A1A05001823 ).

Publisher Copyright:
© 2016 Elsevier B.V.

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Molecular Medicine
Molecular Biology

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

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10.1016/j.bbadis.2016.07.017

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An, H. J., Kwak, S. Y., Yoo, J. O., Kim, J. S., Bae, I. H., Park, M. J., Cho, M. Y., Kim, J., & Han, Y. H. (2016). Novel miR-5582-5p functions as a tumor suppressor by inducing apoptosis and cell cycle arrest in cancer cells through direct targeting of GAB1, SHC1, and CDK2. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1862(10), 1926-1937. https://doi.org/10.1016/j.bbadis.2016.07.017

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title = "Novel miR-5582-5p functions as a tumor suppressor by inducing apoptosis and cell cycle arrest in cancer cells through direct targeting of GAB1, SHC1, and CDK2",

abstract = "MicroRNAs (miRNAs) play pivotal roles in tumorigenesis as either tumor suppressors or oncogenes. In the present study, we discovered and demonstrated the tumor suppressive function of a novel miRNA miR-5582-5p. miR-5582-5p induced apoptosis and cell cycle arrest in cancer cells, but not in normal cells. GAB1, SHC1, and CDK2 were identified as direct targets of miR-5582-5p. Knockdown of GAB1/SHC1 or CDK2 phenocopied the apoptotic or cell cycle arrest-inducing function of miR-5582-5p, respectively. The expression of miR-5582-5p was lower in tumor tissues than in adjacent normal tissues of colorectal cancer patients, while the expression of the target proteins exhibited patterns opposite to that of miR-5582-5p. Intratumoral injection of a miR-5582-5p mimic or induced expression of miR-5582-5p in tumor cells suppressed tumor growth in HCT116 xenografts. Collectively, our results suggest a novel tumor suppressive function for miR-5582-5p and its potential applicability for tumor control.",

author = "An, {Hyun Ju} and Kwak, {Seo Young} and Yoo, {Je Ok} and Kim, {Jae Sung} and Bae, {In Hwa} and Park, {Myung Jin} and Cho, {Mee Yon} and Joon Kim and Han, {Young Hoon}",

note = "Funding Information: This research was supported by the National R&D Program through the Korea Institute of Radiological and Medical Sciences funded by the Ministry of Science, ICT & Future Planning, Republic of Korea ( 1711031811 , 1711031819 ) and in part by a grant to J. Kim from the National Research Foundation of Korea ( NRF2015R1A2A1A05001823 ). Publisher Copyright: {\textcopyright} 2016 Elsevier B.V.",

year = "2016",

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doi = "10.1016/j.bbadis.2016.07.017",

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An, HJ, Kwak, SY, Yoo, JO, Kim, JS, Bae, IH, Park, MJ, Cho, MY, Kim, J & Han, YH 2016, 'Novel miR-5582-5p functions as a tumor suppressor by inducing apoptosis and cell cycle arrest in cancer cells through direct targeting of GAB1, SHC1, and CDK2', Biochimica et Biophysica Acta - Molecular Basis of Disease, vol. 1862, no. 10, pp. 1926-1937. https://doi.org/10.1016/j.bbadis.2016.07.017

Novel miR-5582-5p functions as a tumor suppressor by inducing apoptosis and cell cycle arrest in cancer cells through direct targeting of GAB1, SHC1, and CDK2. / An, Hyun Ju; Kwak, Seo Young; Yoo, Je Ok et al.
In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1862, No. 10, 01.10.2016, p. 1926-1937.

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

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T1 - Novel miR-5582-5p functions as a tumor suppressor by inducing apoptosis and cell cycle arrest in cancer cells through direct targeting of GAB1, SHC1, and CDK2

AU - An, Hyun Ju

AU - Kwak, Seo Young

AU - Yoo, Je Ok

AU - Kim, Jae Sung

AU - Bae, In Hwa

AU - Park, Myung Jin

AU - Cho, Mee Yon

AU - Kim, Joon

AU - Han, Young Hoon

N1 - Funding Information: This research was supported by the National R&D Program through the Korea Institute of Radiological and Medical Sciences funded by the Ministry of Science, ICT & Future Planning, Republic of Korea ( 1711031811 , 1711031819 ) and in part by a grant to J. Kim from the National Research Foundation of Korea ( NRF2015R1A2A1A05001823 ). Publisher Copyright: © 2016 Elsevier B.V.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - MicroRNAs (miRNAs) play pivotal roles in tumorigenesis as either tumor suppressors or oncogenes. In the present study, we discovered and demonstrated the tumor suppressive function of a novel miRNA miR-5582-5p. miR-5582-5p induced apoptosis and cell cycle arrest in cancer cells, but not in normal cells. GAB1, SHC1, and CDK2 were identified as direct targets of miR-5582-5p. Knockdown of GAB1/SHC1 or CDK2 phenocopied the apoptotic or cell cycle arrest-inducing function of miR-5582-5p, respectively. The expression of miR-5582-5p was lower in tumor tissues than in adjacent normal tissues of colorectal cancer patients, while the expression of the target proteins exhibited patterns opposite to that of miR-5582-5p. Intratumoral injection of a miR-5582-5p mimic or induced expression of miR-5582-5p in tumor cells suppressed tumor growth in HCT116 xenografts. Collectively, our results suggest a novel tumor suppressive function for miR-5582-5p and its potential applicability for tumor control.

AB - MicroRNAs (miRNAs) play pivotal roles in tumorigenesis as either tumor suppressors or oncogenes. In the present study, we discovered and demonstrated the tumor suppressive function of a novel miRNA miR-5582-5p. miR-5582-5p induced apoptosis and cell cycle arrest in cancer cells, but not in normal cells. GAB1, SHC1, and CDK2 were identified as direct targets of miR-5582-5p. Knockdown of GAB1/SHC1 or CDK2 phenocopied the apoptotic or cell cycle arrest-inducing function of miR-5582-5p, respectively. The expression of miR-5582-5p was lower in tumor tissues than in adjacent normal tissues of colorectal cancer patients, while the expression of the target proteins exhibited patterns opposite to that of miR-5582-5p. Intratumoral injection of a miR-5582-5p mimic or induced expression of miR-5582-5p in tumor cells suppressed tumor growth in HCT116 xenografts. Collectively, our results suggest a novel tumor suppressive function for miR-5582-5p and its potential applicability for tumor control.

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JO - Biochimica et Biophysica Acta - Molecular Basis of Disease

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Novel miR-5582-5p functions as a tumor suppressor by inducing apoptosis and cell cycle arrest in cancer cells through direct targeting of GAB1, SHC1, and CDK2

Abstract

Bibliographical note

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UN SDGs

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