Journal
ONCOTARGET
Volume 6, Issue 11, Pages 8676-8686Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3254
Keywords
miR-129-5p; YAP; TAZ; Cell proliferation; Survival
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Funding
- National Natural Science Foundation of China [81171442]
- Science and Technology Projects Foundation of Guangdong Province [2012B031800501, 2013B021800252]
- Medical Research Foundation of Guangdong Province [A2014226]
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Transcriptional co-activator Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are key oncogenes in mammalian cells. Activities of YAP and TAZ are largely restricted by the Hippo tumor suppressor pathway through phosphorylation-ubiquitination mechanisms. The involvement of microRNA in cancer progression has recently been reported, though whether they have a role in activating YAP and TAZ in human cancer cells remains unclear. Here, we report a microRNA, miR-129-5p, directly represses YAP and TAZ expression, leading to the inactivation of TEA domain (TEAD) transcription, and the downregulation of Hippo downstream genes, connective tissue growth factor (CTGF) and Cyclin A. Furthermore, we reveal miR-129-5p inhibits ovarian cancer cell proliferation, survival and tumorigenicity, and that downregulation of miR-129-5p in ovarian cancer cells highly correlates with malignant progression and poor survival. Hence, we demonstrate a novel mechanism for YAP and TAZ activation in cancers, indicating not only a potentially pivotal role for miR-129-5p in the progression of ovarian cancer, but also offering new therapeutic strategies to circumvent the disease.
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