Wild-type p53 suppresses the epithelial-mesenchymal transition and stemness in PC-3 prostate cancer cells by modulating miR‑145

Dong Ren, Min Wang, Wei Guo, Xiaohui Zhao, Xiang'an Tu, Shuai Huang, Xuenong Zou, Xinsheng Peng
International Journal of Oncology 2013, 42 (4): 1473-81
The principal problem arising from prostate cancer (PCa) is its propensity to metastasize to bone and the mechanism(s) need to be further elucidated. The tumor suppressor p53 plays an important role in regulating the epithelial-mesenchymal transition (EMT) and cancer cell stemness, which have been proposed to play critical roles in cancer metastasis. MiR-145, a direct target of p53, represses bone metastasis of PCa and is involved in regulating EMT and cancer cell stemness. However, it is unknown whether wild‑type p53 (WT-p53) plays a role in regulating invasion, EMT and cancer cell stemness of PCa cells and whether miR-145 mediates the function of WT-p53. In the present study, we found that ectopic expression of WT-p53 inhibited the migration and invasion, and enhanced the adhesion of p53-null PC-3 cells derived from PCa bone metastasis. Furthermore, WT-p53 suppressed the expression of the mesenchymal markers fibronectin, vimentin, N-cadherin, ZEB2 and upregulated the expression of the epithelial marker E-cadherin in PC-3 cells. Moreover, WT-p53 also suppressed colony formation, tumor sphere formation and expression of CSC markers and stemness factors including CD44, Oct4, c-Myc and Klf4 in PC-3 cells. Importantly, WT-p53 upregulated the expression of miR-145, and the inhibitory effects of WT-p53 on migration, invasion, EMT and stemness of PC-3 cells were reversed by anti-miR-145. Together, our findings demonstrate that WT-p53 suppresses migration, invasion, EMT and stemness in PC-3 cells at least partially through modulating miR-145. These results suggest that loss of WT-p53 may promote the bone metastasis of PCa at least partially through repressing miR-145 to elevate EMT and stemness of cancer cells.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"