Department of Radiotherapy and Chemotherapy, First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang, China (mainland).
Department of Anus and Intestine Surgery, First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang, China (mainland).
Med Sci Monit. 2018 Jun 12;24:3987-3996. doi: 10.12659/MSM.906736.
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 AND 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.
TBC1 结构域家族成员 24（TBC1D24）的致病性突变会影响其与 ARF6 的结合，从而导致神经元发育严重受损。然而，目前尚无关于 TBC1D24 在癌症中的表达和功能的报道。本研究旨在评估沉默乳腺癌 MCF-7 细胞中 TBC1D24 表达后对细胞增殖、迁移和侵袭的影响，并阐明 TBC1D24 在乳腺癌中的潜在机制。
通过 S-P 免疫组化检测乳腺癌组织和相邻非肿瘤组织中 TBC1D24 的表达。沉默乳腺癌 MCF-7 细胞中 TBC1D24 后，测定其恶性行为，包括增殖、迁移和侵袭能力。沉默 TBC1D24 后测定 IGF1R 的表达。转染 miR-30a 模拟物或抑制剂后检测 TBC1D24 和 IGF1R 的表达。通过肿瘤异种移植研究评估 TBC1D24 对 MCF-7 细胞体内生长的影响。
TBC1D24 表达升高与乳腺癌不良预后相关。TBC1D24 高表达与乳腺癌患者不良 OS 和 RFS 显著相关（p<0.05）。沉默 TBC1D24 抑制 MCF-7 细胞的增殖、迁移和侵袭能力。转染 miR-30a 模拟物后，TBC1D24 和 IGF1R 的表达降低；而转染 miR-30a 抑制剂后，TBC1D24 和 IGF1R 的表达增加（p<0.05）。沉默 TBC1D24 抑制 IGF1R、PI3K 和 p-AKT 的表达（p<0.05）。沉默 TBC1D24 消除了 MCF-7 细胞的致瘤性。沉默 TBC1D24 表达后肿瘤的平均体积和重量降低（P<0.05）。
沉默 TBC1D24 抑制 MCF-7 细胞在体外和体内的生长。TBC1D24 通过 IGF1R/PI3K/AKT 通路促进乳腺癌的生长。TBC1D24 是乳腺癌潜在的治疗靶点。
