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 | |
| Publication status | Published - 2016 Oct 1 |
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Keywords
- CDK2
- GAB1
- MicroRNA
- miR-5582-5p
- SHC1
- Tumor suppressor
ASJC Scopus subject areas
- Molecular Biology
- Molecular Medicine
Cite this
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; Kim, Jae Sung; Bae, In Hwa; Park, Myung Jin; Cho, Mee Yon; Kim, Joon; Han, Young Hoon.
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
}
TY - JOUR
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
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.
KW - CDK2
KW - GAB1
KW - MicroRNA
KW - miR-5582-5p
KW - SHC1
KW - Tumor suppressor
UR - http://www.scopus.com/inward/record.url?scp=84979948628&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84979948628&partnerID=8YFLogxK
U2 - 10.1016/j.bbadis.2016.07.017
DO - 10.1016/j.bbadis.2016.07.017
M3 - Article
AN - SCOPUS:84979948628
VL - 1862
SP - 1926
EP - 1937
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
SN - 0925-4439
IS - 10
ER -