Key Laboratory for Biorheological Science and Technology of Ministry of Education, Bioengineering College of Chongqing University, Chongqing 400044, P.R. China.
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P.R. China.
Int J Mol Med. 2022 Sep;50(3). doi: 10.3892/ijmm.2022.5171. Epub 2022 Jul 7.
Breast cancer is the most frequent cause of cancer‑related mortality among women worldwide. The present study aimed to explore the role of magnesium transporter protein 1 (MAGT1) in breast cancer and to illustrate the potential underlying molecular mechanisms. Bioinformatic analysis was performed to explore the association between MAGT1 expression and patients with breast cancer. MTT, colony formation, wound healing and Transwell assays were performed to examine the proliferative, migratory and invasive abilities of MCF‑7 cells. Western blot analysis was conducted to determine the corresponding protein expression. Chromatin immunoprecipitation and luciferase reporter assays were carried out to reveal the interaction between MAGT1 and the Kruppel‑like factor 16 (KLF16). In addition, an experimental animal model was established by the subcutaneous injection of MCF‑7 cells into BALB/c nude mice, and tumor weight and size were measured. The results revealed that MAGT1 expression was upregulated in breast cancer. MAGT1 knockdown significantly suppressed the MCF‑7 cell proliferative, migratory and invasive abilities, and downregulated the protein expression of Ki67, proliferating cell nuclear antigen, MMP2 and MMP9. MAGT1 knockdown also markedly suppressed tumor growth . Moreover, KLF6 could bind to the MAGT1 promoter and positively regulate MAGT1 expression. The inhibitory effects of KLF6 knockdown on cell proliferation, migration and invasion , and tumor growth were partly abolished by MAGT1 overexpression. On the whole, the findings of the present study suggest that MAGT1 knockdown exerts notable inhibitory effects on the progression of breast cancer, providing a potential therapeutic target for the treatment of breast cancer.
乳腺癌是全球女性癌症相关死亡的最常见原因。本研究旨在探讨镁转运蛋白 1（MAGT1）在乳腺癌中的作用，并阐明潜在的分子机制。进行了生物信息学分析，以探讨 MAGT1 表达与乳腺癌患者之间的关联。通过 MTT、集落形成、划痕愈合和 Transwell 测定法来检测 MCF-7 细胞的增殖、迁移和侵袭能力。通过 Western blot 分析来确定相应的蛋白表达。进行染色质免疫沉淀和荧光素酶报告基因测定来揭示 MAGT1 与 Kruppel 样因子 16（KLF16）之间的相互作用。此外，通过将 MCF-7 细胞皮下注射到 BALB/c 裸鼠中来建立实验动物模型，并测量肿瘤重量和大小。结果表明，MAGT1 在乳腺癌中表达上调。MAGT1 敲低显著抑制 MCF-7 细胞的增殖、迁移和侵袭能力，并下调 Ki67、增殖细胞核抗原、MMP2 和 MMP9 的蛋白表达。MAGT1 敲低还显著抑制肿瘤生长。此外，KLF6 可以结合 MAGT1 启动子并正向调节 MAGT1 表达。MAGT1 过表达部分消除了 KLF6 敲低对细胞增殖、迁移和侵袭以及肿瘤生长的抑制作用。总的来说，本研究的结果表明，MAGT1 敲低对乳腺癌的进展具有显著的抑制作用，为治疗乳腺癌提供了一个潜在的治疗靶点。
