Downregulation of TBC1 Domain Family Member 24 (BC1D24) Inhibits Breast Carcinoma Growth via IGF1R/PI3K/AKT Pathway

作者：Qu, Xiusheng; Zhao, Bin; Hu, Min; Ji, Zhiwu; Xu, Jian; Xia, Weibin; Qu, Yikun^*

来源：MEDICAL SCIENCE MONITOR, 2018, 24: 3987-3996.

DOI：10.12659/MSM.906736

• Brain Neoplasms
• Cell Migration Assays
• MicroRNAs

Background: TBC1 domain family member 24 (TBC1D24) pathogenic mutations affect its binding to ARF6 and then result in severe impairment of neuronal development. However, there are no reports about the expression and function of TBC1D24 in cancer. The aim of the present study was to evaluate the effect of proliferation, migration, and invasion after silencing TBC1D24 expression in breast cancer MCF-7 cells, and to elucidate the potential mechanism of TBC1D24 in breast cancer. @@@ Material/Methods: The expression of TBC1D24 in breast cancer tissues and the adjacent non-tumor tissues was determined by S-P immunohistochemistry. The malignant behavior, including proliferation, migration, and invasion ability, was determined after silencing TBC1D24 in breast cancer MCF-7 cells. The expression of IGF1R was determined after silencing TBC1D24. The expression of TBC1D24 and IGF1R was detected after transfecting miR-30a mimics or inhibitors. The effect of TBC1D24 on MCF-7 cells growth in vivo was evaluated by a tumor xenograft study. @@@ Results: TBC1D24 expression was elevated and was associated with poor outcome in breast carcinoma. TBC1D24 high expression was significantly correlated with unfavorable OS and RFS for breast cancer patients (p<0.05). Silencing TBC1D24 inhibited the proliferation, migration, and invasion ability of MCF-7 cells. TBC1D24 and IGF1R expression were decreased when transfected with miR-30a mimics. However, TBC1D24 and IGF1R expression were increased when transfected with miR-30a inhibitors (p<0.05). Knockdown of TBC1D24 inhibited the expression of IGF1R, PI3K, and p-AKT (p<0.05). Knockdown of TBC1D24 abolished tumorigenicity of MCF-7 cells. The average volume and weight of tumors was lower after silencing TBC1D24 expression (P<0.05). @@@ Conclusions: Silencing TBC1D24 inhibited MCF-7 cells growth in vitro and in vivo. TBC1D24 promoted breast carcinoma growth through the IGF1R/PI3K/AKT pathway. TBC1D24 is a potential therapeutic target for breast cancer.

• 出版日期2018-6-12
• 单位佳木斯大学