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. 2009 Oct;129(10):2497-506.
doi: 10.1038/jid.2009.83. Epub 2009 Apr 16.

V体育平台登录 - Modification of alternative splicing of Mcl-1 pre-mRNA using antisense morpholino oligonucleotides induces apoptosis in basal cell carcinoma cells

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Modification of alternative splicing of Mcl-1 pre-mRNA using antisense morpholino oligonucleotides induces apoptosis in basal cell carcinoma cells

Jeng-Jer Shieh et al. J Invest Dermatol. 2009 Oct.
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Abstract (V体育官网)

Myeloid cell leukemia-1 (Mcl-1, Mcl-1L) is an anti-apoptotic protein of the Bcl-2 family that acts as a critical molecule in apoptosis control. Mcl-1 pre-mRNA can undergo alternative splicing to yield the short isoform, Mcl-1S, which resembles BH3-only pro-apoptotic proteins and induces apoptosis. Overexpression of Mcl-1 may play a role in various human tumors, and Mcl-1 may serve as a target in cancer therapy. In this study, we found an imbalance between the expression levels of Mcl-1L and Mcl-1S in the skin basal cell carcinoma (BCC) cell line when compared with primary keratinocytes. We showed that overexpression of Mcl-1S induces apoptosis in BCC cells. Finally, we showed that Mcl-1 antisense morpholino oligonucleotides (AMOs) can specifically target Mcl-1 pre-mRNA and shift the splicing pattern from Mcl-1L to Mcl-1S mRNA and protein. This shift increases the level of pro-apoptotic Mcl-1S and reduces the level of anti-apoptotic Mcl-1L, which induces apoptosis in BCC cells and AGS cells, a human gastric adenocarcinoma epithelial cell line. Thus, this report provides a strategy for cancer therapy in which AMOs change the alternative splicing pattern of Mcl-1 pre-mRNA and thereby induce apoptosis. VSports手机版.

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