Int J Biol Sci 2020; 16(12):2084-2093. doi:10.7150/ijbs.44204
ZNF367-induced transcriptional activation of KIF15 accelerates the progression of breast cancer
1. Breast Disease Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
2. Laboratory of Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
Zeng H, Li T, Zhai D, Bi J, Kuang X, Lu S, Shan Z, Lin Y. ZNF367-induced transcriptional activation of KIF15 accelerates the progression of breast cancer. Int J Biol Sci 2020; 16(12):2084-2093. doi:10.7150/ijbs.44204. Available from http://www.ijbs.com/v16p2084.htm
Breast cancer (BC) is one of the most common female cancers, and its incidence has been increasing in recent years. Although treatments are continuously improving, the prognosis of patients in the advanced stage is still unsatisfactory. Thus, an in-depth understanding of its molecular mechanisms is necessary for curing breast cancer. KIF15 is a tetrameric spindle motor which can regulate mitosis in cellular process and exert the crucial functions in several cancers. The purpose of our research was to investigate the functions of KIF15 in breast cancer. We tested the expression of KIF15 in breast cancer tissues and the survival rate of breast cancer patients with high or low level of KIF15 through TCGA data. What's more, western blot and immunohistochemistry assay were utilized to evaluate the protein level and mRNA level of KIF15 in breast cancer tissues. Then CCK-8, wound healing, transwell and flow cytometry experiments were adopted separately to test cell viability, migration, invasion and cell cycle distribution. We discovered that KIF15 was highly expressed in breast cancer tissues and high level KIF15 was associated with a low survival rate of breast cancer patients. Moreover, silence of KIF15 suppressed cell viability, migration, invasion and cell cycle distribution. Following, we discovered that ZNF367 was the upstream transcription factor of KIF15. In addition, silenced ZNF367 could also repress the growth of breast cancer cells. And rescue experiments indicated that overexpressed KIF15 could counteract the inhibition effect of silencing ZNF367 on the progression of breast cancer. Importantly, we discovered that KIF15 and ZNF367 were associated with the regulation of cell cycle. In short, ZNF367-activated KIF15 accelerated the progression of breast cancer by regulating cell cycle progress.
Keywords: ZNF367, KIF15, breast cancer, cell cycle