Modification of Mcl-1 alternative splicing induces apoptosis and suppresses tumor proliferation in gastric cancer
Yonghong Li, Xiaoling Gao, Chaojun Wei, Rui Guo, Hui Xu, Zhongtian Bai, Jianye Zhou, Jun Zhu, Wanxia Wang, Yu Wu, Jingzhe Li, Zhongliang Zhang, Xiaodong Xie
Abstract
data showed that a shift in splicing from Mcl-1L to Mcl-1S induced by treatment with Mcl-1-specific steric-blocking oligonucleotides (SBOs) efficiently decreased Mcl-1L expression, increased Mcl-1S expression, and accelerated tumor cell apoptosis in a dose-dependent manner. Additionally, mouse xenotransplant models confirmed that modification of Mcl-1 alternative splicing increased tumor cell death and suppressed tumor proliferation. This study demonstrated that the modification of Mcl-1 splicing might stimulate the pro-apoptotic factor and inhibit the anti-apoptotic protein to induce significant apoptosis. Thus, this finding provided a strategy for cancer therapy, according to which SBOs could be used to change the Mcl-1 splicing pattern, thereby inducing apoptosis.