Professor Fu Songbin’s team of Laboratory of Medical Genetics, Harbin Medical University, recently has revealed the mechanism of micronuclei expulsion of double minute chromosomes (DMs) from the tumor cells. This interesting discovery has been published on International Journal of Cancer entitled “Expulsion of micronuclei containing amplified genes contributes to a decrease in double minute chromosomes from malignant tumor cells”, March 2014. This work was in collaboration with Dr. Ki-Young Lee (Department of Cell Biology & Anatomy, University of Calgary, Canada).
Double minute chromosomes (DMs) are a hallmark of gene amplification. The relationship between the formation of DMs and the amplification of DM-carried genes remains to be clarified. In the study, they identified the amplification regions and the DM-carried genes that were amplified and overexpressed in human colorectal cell line and human malignant primitive neuroectodermal tumor cell line. Using RNA interference, they downregulated seven DM-carried genes individually and then investigated the formation of DMs, the amplification of the DM-carried genes, DNA damage and the physiological function of these genes. They found that suppressing the expression of DM-carried genes led to a decrease in the number of DMs and reduced the amplification of the DM-carried genes through the micronuclei expulsion of DMs from the tumor cells. They further detected an increase in the number of cH2AX foci in the knockdown cells, which provides a strong link between DNA damage and the loss of DMs. In addition, the loss of DMs and the reduced amplification and expression of the DM-carried genes resulted in a decrease in cell proliferation and invasion ability.
This work was supported by the International Science & Technology Cooperation Program of China, Program for Changjiang Scholars and Innovative Research Team in University, the National Natural Science Foundation of China, the New Century Support Program for the Excellent Scholar, Ministry of Education of China.
Publication link: http://onlinelibrary.wiley.com/doi/10.1002/ijc.28467/abstract