Abstract
Ovarian carcinoma is the most lethal gynaecological malignancy. Better understanding of the molecular pathogenesis of this disease and effective targeted therapies are needed to improve patient outcomes. MicroRNAs play important roles in cancer progression and have the potential for use as either therapeutic agents or targets. Studies in other cancers have suggested that miR-506 has anti-tumour activity, but its function has yet to be elucidated. We found that deregulation of miR-506 in ovarian carcinoma promotes an aggressive phenotype. Ectopic over-expression of miR-506 in ovarian cancer cells was sufficient to inhibit proliferation and to promote senescence. We also demonstrated that CDK4 and CDK6 are direct targets of miR-506, and that miR-506 can inhibit CDK4/6-FOXM1 signalling, which is activated in the majority of serous ovarian carcinomas. This newly recognized miR-506-CDK4/6-FOXM1 axis provides further insight into the pathogenesis of ovarian carcinoma and identifies a potential novel therapeutic agent.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 308-318 |
| Number of pages | 11 |
| Journal | Journal of Pathology |
| Volume | 233 |
| Issue number | 3 |
| DOIs | |
| State | Published - 2014 |
| Externally published | Yes |
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Keywords
- FOXM1
- miR-506
- ovarian carcinoma
- proliferation
- senescence
ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
MiR-506 suppresses proliferation and induces senescence by directly targeting the CDK4/6-FOXM1 axis in ovarian cancer. / Liu, Guoyan; Sun, Yan; Ji, Ping; Li, Xia; Cogdell, David; Yang, Da; Parker Kerrigan, Brittany C.; Shmulevich, Ilya; Chen, Kexin; Sood, Anil K.; Xue, Fengxia; Zhang, Wei.
In: Journal of Pathology, Vol. 233, No. 3, 2014, p. 308-318.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MiR-506 suppresses proliferation and induces senescence by directly targeting the CDK4/6-FOXM1 axis in ovarian cancer
AU - Liu, Guoyan
AU - Sun, Yan
AU - Ji, Ping
AU - Li, Xia
AU - Cogdell, David
AU - Yang, Da
AU - Parker Kerrigan, Brittany C.
AU - Shmulevich, Ilya
AU - Chen, Kexin
AU - Sood, Anil K.
AU - Xue, Fengxia
AU - Zhang, Wei
PY - 2014
Y1 - 2014
N2 - Ovarian carcinoma is the most lethal gynaecological malignancy. Better understanding of the molecular pathogenesis of this disease and effective targeted therapies are needed to improve patient outcomes. MicroRNAs play important roles in cancer progression and have the potential for use as either therapeutic agents or targets. Studies in other cancers have suggested that miR-506 has anti-tumour activity, but its function has yet to be elucidated. We found that deregulation of miR-506 in ovarian carcinoma promotes an aggressive phenotype. Ectopic over-expression of miR-506 in ovarian cancer cells was sufficient to inhibit proliferation and to promote senescence. We also demonstrated that CDK4 and CDK6 are direct targets of miR-506, and that miR-506 can inhibit CDK4/6-FOXM1 signalling, which is activated in the majority of serous ovarian carcinomas. This newly recognized miR-506-CDK4/6-FOXM1 axis provides further insight into the pathogenesis of ovarian carcinoma and identifies a potential novel therapeutic agent.
AB - Ovarian carcinoma is the most lethal gynaecological malignancy. Better understanding of the molecular pathogenesis of this disease and effective targeted therapies are needed to improve patient outcomes. MicroRNAs play important roles in cancer progression and have the potential for use as either therapeutic agents or targets. Studies in other cancers have suggested that miR-506 has anti-tumour activity, but its function has yet to be elucidated. We found that deregulation of miR-506 in ovarian carcinoma promotes an aggressive phenotype. Ectopic over-expression of miR-506 in ovarian cancer cells was sufficient to inhibit proliferation and to promote senescence. We also demonstrated that CDK4 and CDK6 are direct targets of miR-506, and that miR-506 can inhibit CDK4/6-FOXM1 signalling, which is activated in the majority of serous ovarian carcinomas. This newly recognized miR-506-CDK4/6-FOXM1 axis provides further insight into the pathogenesis of ovarian carcinoma and identifies a potential novel therapeutic agent.
KW - FOXM1
KW - miR-506
KW - ovarian carcinoma
KW - proliferation
KW - senescence
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UR - http://www.scopus.com/inward/citedby.url?scp=84902344416&partnerID=8YFLogxK
U2 - 10.1002/path.4348
DO - 10.1002/path.4348
M3 - Article
VL - 233
SP - 308
EP - 318
JO - Journal of Pathology
JF - Journal of Pathology
SN - 0022-3417
IS - 3
ER -