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A novel role for microRNA-129-5p in inhibiting ovarian cancer cell proliferation and survival via direct suppression of transcriptional co-activators YAP and TAZ.

Tan G, Cao X, Dai Q, Zhang B, Huang J, Xiong S, Zhang Yy, Chen W, Yang J, Li H - Oncotarget (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Clinical relevance of miR-129-5p, YAP, TAZ, CTGF and Cyclin A in ovarian cancer(A and B) Expression analysis (A) and correlation (B) of miR-129-5p expression and YAP, TAZ protein expression, and CTGF, Cyclin A mRNA levels in nine freshly collected human ovarian cancer tissue samples (T) The ratio of first sample (YAP/α-tubulin, TAZ/α-tubulin) was considered as 1.0. α-Tubulin were used as loading controls. Each bar represents the mean ± SD of three independent experiments.
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Figure 7: Clinical relevance of miR-129-5p, YAP, TAZ, CTGF and Cyclin A in ovarian cancer(A and B) Expression analysis (A) and correlation (B) of miR-129-5p expression and YAP, TAZ protein expression, and CTGF, Cyclin A mRNA levels in nine freshly collected human ovarian cancer tissue samples (T) The ratio of first sample (YAP/α-tubulin, TAZ/α-tubulin) was considered as 1.0. α-Tubulin were used as loading controls. Each bar represents the mean ± SD of three independent experiments.

Mentions: Finally, we examined whether miR-129-5p-mediated suppression of YAP and TAZ in ovarian cancers are clinically relevant. As shown in Figure 7A–7B and Supplementary Figure 5, miR-129-5p levels in nine freshly collected ovarian cancer samples were inversely correlated with the expression levels of YAP (r = –0.706, p = 0.003) and TAZ (r = –0.683, p = 0.005), and mRNA levels of Hippo downstream genes CTGF (r = –0.832, p < 0.001) and Cyclin A (r = –0.801, p < 0.001). Our results suggest that miR-129-5p downregulation increases YAP and TAZ expression, consequently resulting in an aggressive ovarian cancer with poor prognosis.


A novel role for microRNA-129-5p in inhibiting ovarian cancer cell proliferation and survival via direct suppression of transcriptional co-activators YAP and TAZ.

Tan G, Cao X, Dai Q, Zhang B, Huang J, Xiong S, Zhang Yy, Chen W, Yang J, Li H - Oncotarget (2015)

Clinical relevance of miR-129-5p, YAP, TAZ, CTGF and Cyclin A in ovarian cancer(A and B) Expression analysis (A) and correlation (B) of miR-129-5p expression and YAP, TAZ protein expression, and CTGF, Cyclin A mRNA levels in nine freshly collected human ovarian cancer tissue samples (T) The ratio of first sample (YAP/α-tubulin, TAZ/α-tubulin) was considered as 1.0. α-Tubulin were used as loading controls. Each bar represents the mean ± SD of three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496175&req=5

Figure 7: Clinical relevance of miR-129-5p, YAP, TAZ, CTGF and Cyclin A in ovarian cancer(A and B) Expression analysis (A) and correlation (B) of miR-129-5p expression and YAP, TAZ protein expression, and CTGF, Cyclin A mRNA levels in nine freshly collected human ovarian cancer tissue samples (T) The ratio of first sample (YAP/α-tubulin, TAZ/α-tubulin) was considered as 1.0. α-Tubulin were used as loading controls. Each bar represents the mean ± SD of three independent experiments.
Mentions: Finally, we examined whether miR-129-5p-mediated suppression of YAP and TAZ in ovarian cancers are clinically relevant. As shown in Figure 7A–7B and Supplementary Figure 5, miR-129-5p levels in nine freshly collected ovarian cancer samples were inversely correlated with the expression levels of YAP (r = –0.706, p = 0.003) and TAZ (r = –0.683, p = 0.005), and mRNA levels of Hippo downstream genes CTGF (r = –0.832, p < 0.001) and Cyclin A (r = –0.801, p < 0.001). Our results suggest that miR-129-5p downregulation increases YAP and TAZ expression, consequently resulting in an aggressive ovarian cancer with poor prognosis.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus