Abstract
Objective
The aim of the study was to observe the effect of Bmi1 reduction on the self-renewal and tumorigenicity ability of lung cancer stem cells (LCSCs) in human lung adenocarcinoma.
Methods
Human lung adenocarcinoma cells A549 were consecutively passaged in NOD/SCID mice treated with Paclitaxel weekly. The proportions of LCSCs in A549 cells and the cells from the third passage (A549-3rd) were compared. The expression of Bmi1 in LCSCs was silenced by intratumoral injection with lentivirus-delivered Bmi1 small hairpin RNA (shRNA). RT-PCR and Western blot were used to test the mRNA and protein expressions of Bmi1 in LCSCs. The protein level of p16INK4A was analyzed by Western blotting. The selfrenewal and tumorigenicity ability of LCSCs were evaluated by counting the sphere formation rate in serum-free medium and the tumor formation rate in NOD/SCID mice.
Results
In vivo passaging of A549 cells under chemotherapy pressure enriched for LCSCs. The expression of Bmi1 in LCSCs increased. Down-regulation of Bmi1 by RNA interference resulted in reduced self-renewal and tumorigenicity ability of LCSCs and paralleled the increased expression of p16INK4A, a Bmi1 target.
Conclusion
Bmi1 regulates self-renewal and tumorigenicity of LCSCs by silencing some target genes, including p16INK4A.
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Supported by grants from the National Natural Science Foundation of China (No. China (No. 30772144) and Natural Science Foundation of Chongqing (No. CSTC, 2009BB5148).
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Zhou, J., Xu, Y., Hao, P. et al. Inhibition of lung cancer stem cells self-renewal and tumorigenicity by lentivirus-delivered Bmi1 shRNA. Chin. -Ger. J. Clin. Oncol. 10, 636–642 (2011). https://doi.org/10.1007/s10330-011-0861-0
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DOI: https://doi.org/10.1007/s10330-011-0861-0