Regulation of HPV16 E6 and MCL1 by SF3B1 inhibitor in head and neck cancer cells

• DOI: 10.1038/srep06098
• Publication Date: 2014-08-20T09:08:06Z
• Authors: Yang Gao; Sumita Trivedi; Robert L. Ferris; Kazunori Koide
• Keywords: MCL1

ABT-737 inhibits the anti-apoptotic proteins B-cell lymphoma 2 (BCL-2) and BCL-XL. Meayamycin B switches splicing pattern of myeloid cell leukemia factor 1 (MCL1) pre-mRNA. Specifically, inhibition 3B subunit (SF3B1) with meayamycin promotes generation proapoptotic, short variant (MCL1-S) diminishes antiapoptotic, long (MCL1-L). This action was previously associated cytotoxicity in non-small lung carcinoma lines. induced apoptosis response to an ablation MCL1-L by B. In this study, we further exploited synergistic combination head neck squamous (HNSCC), up 90% which overexpress MCL1 a panel seven HNSCC lines, rapidly triggered Bax/Bak-mediated that overcame resistance from HPV16-positive against each agent alone. Both RT-PCR Western blotting showed up-regulated MCL1-S down-regulated MCL1-L. Significantly, discovered SF3B1 involved oncogenic HPV16 E6 produce non-oncogenic E6*, indicating may inhibit HPV16-induced tumorigenesis.