Msi1 inhibits cervical cancer cell apoptosis by downregulating BAK through AKT signaling

Xian Liu; Yanru Zhang; PengSheng Zheng; Nan Cui

doi:10.7150/jca.52950

Msi1 inhibits cervical cancer cell apoptosis by downregulating BAK through AKT signaling

J Cancer. 2021 Mar 1;12(8):2422-2429. doi: 10.7150/jca.52950. eCollection 2021.

Authors

Xian Liu^{1

2}, Yanru Zhang^{1

2}, PengSheng Zheng^{1

2}, Nan Cui^{1

2}

Affiliations

¹ Department of Reproductive Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, PR China.
² Section of Cancer Stem Cell Research, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of the People's Republic of China, 710061 Xi'an, Shaanxi, PR China.

Abstract

Musashi-1 (Msi1) is an RNA binding protein that functions as a regulator in multiple carcinomas. Our previous study demonstrated that Msi1 could promote the proliferation of cervical cancer cells by targeting the cell cycle proteins P21, P27 and P53. However, the mechanisms by which Msi1 affects the survival of cervical cancer cells, such as apoptosis, are still unclear. In this study, we found that the expression of Msi1 inhibited cervical cancer cell apoptosis in vitro and in vivo. Furthermore, the expression of Msi1 downregulated the expression of PTEN, while AKT signaling was activated, which resulted in a reduction in the proapoptotic protein BAK. In addition, rescue the expression of BAK in Msi1 expressing cervical cancer cells induced the increase of apoptosis cells. These findings indicate that Msi1 regulates cervical cancer cell apoptosis by inhibiting PTEN and activating AKT signaling, which leads to the downregulation of BAK.

Keywords: AKT signaling; Msi1; apoptosis; cervical cancer.