HEF1 promotes epithelial mesenchymal transition and bone invasion in prostate cancer under the regulation of microRNA‐145

The principal problem arising from prostate cancer (PCa) is its propensity to metastasize to bones, and it's crucial to understand the mechanism of tumor progression to metastasis in order to develop therapies that may reduce the morbidity and mortality of PCa patients. Although we had identified that microRNA(miR)‐145 could repress bone metastasis of PCa via regulating epithelial–mesenchymal transition (EMT) in previous study, it is still unknown how miR‐145 regulated EMT. In the present study, we constructed a luciferase reporter system and identified HEF1 as a direct target of miR‐145. More importantly, HEF1 was shown to promote migration, invasion and EMT of PC‐3 cells, a human PCa cell line originated from a bone metastatic PCa specimen. And HEF1 was also shown to partially mediate miR‐145 suppression of EMT and invasion. Furthermore, inhibition of HEF1 repressed bone invasion of PC‐3 cells in vivo. Expression of HEF1 was negatively correlated with miR‐145 in primary PCa and bone metastatic specimens, but HEF1 was higher in samples which were more likely to commit to bone metastasis or those with higher free prostate‐specific antigen (fPSA) levels and Gleason scores. Taken together, these findings indicate that HEF1 promotes EMT and bone invasion in prostate cancer by directly targeted by miR‐145, and miR‐145 suppresses EMT and invasion, at least in part, through repressing HEF1. J. Cell. Biochem. 114: 1606–1615, 2013. © 2013 Wiley Periodicals, Inc.     

Chromosome dynamic changes in two cultured chinese human embryonic stem cell lines: Single nucleotide polymorphism, copy number variation and loss of heterozygosity

The quality and safety of human embryonic stem cells (hESCs) in clinical application depend on gene stability. Two Chinese hESC lines, Zh1 and Zh21, were incubated over a long period. We observed and compared the gene stability in the passage numbers 20, 17 for Zh1 cell line and passage numbers 27, 60, 68 for Zh21 cell line. Single nucleotide polymorphisis analysis indicated that hESCs in early passages had relative gene stability; and with the increase in passage number, gene instability became strong. We also found that there were copy number variations (CNVs) in both Zh21 and Zh1. We analyzed the CNVs of Chinese Han Beijing man (CHB; normal Chinese people) and found that the all CNV forms were the loss in Zh21, Zh1, and CHB. We also analyzed and compared the related pathways of the mutant genes. We propose three steps to ensure hESC safety. Firstly, besides the conventional methods such as pluripotent genes, chromosome G‐banding and teratoma, high‐resolution DNA chip analysis should also be adopted; secondly, chromosomal properties are monitored every 10 passages in less than passage 50 and every 5 passages in more than passage 50; thirdly, the related pathways of mutant genes should be observed because only the mutant genes with variations of their related pathways may affected cell functions. J. Cell. Biochem. 113: 3520–3527, 2012. © 2012 Wiley Periodicals, Inc.