Department of Hematology, Laboratory for Stem Cell and Regenerative Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261042, China.
Department of Hematology, Laboratory for Stem Cell and Regenerative Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261042, China; Graduate School, Weifang Medical University, Weifang, Shandong 261053, China.
Leuk Res. 2023 Sep;132:107343. doi: 10.1016/j.leukres.2023.107343. Epub 2023 Jun 17.
Forkhead box K2 (FOXK2) is a transcription factor involved in regulating the pathophysiological processes in many types of cancers. Functioning as either an oncogene or tumor suppressor, FOXK2 is involved in cell proliferation, metastasis, DNA damage, metabolism, and autophagy. However, the functions of FOXK2 in multiple myeloma (MM) are still unexplored. Here we show that FOXK2 silencing by small interfering RNA (siRNA) prevented the expression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) via dephosphorylation of an AMP-activated protein kinase (AMPK). Consistently, suppression of FOXK2 inhibited glycolysis and cell proliferation in MM cells. Furthermore, the correlation between FOXK2 expression and disease progression in MM was evaluated using the TCGA (The Cancer Genome Atlas) database. Taken together, we identified a novel FOXK2-dependent signaling pathway involved in the regulation of PFKFB3 expression in response to glycolysis, which might serve as a potential therapeutic target in MM.
叉头框蛋白 K2（FOXK2）是一种参与调节多种癌症病理生理过程的转录因子。FOXK2 作为癌基因或肿瘤抑制因子，参与细胞增殖、转移、DNA 损伤、代谢和自噬。然而，FOXK2 在多发性骨髓瘤（MM）中的功能仍未被探索。在这里，我们通过小干扰 RNA（siRNA）沉默 FOXK2，发现其通过去磷酸化 AMP 激活的蛋白激酶（AMPK），阻止了 6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶 3（PFKFB3）的表达。一致地，抑制 FOXK2 抑制了 MM 细胞中的糖酵解和细胞增殖。此外，我们还使用 TCGA（癌症基因组图谱）数据库评估了 FOXK2 表达与 MM 疾病进展之间的相关性。总之，我们鉴定了一种新的 FOXK2 依赖性信号通路，该通路参与调节糖酵解中 PFKFB3 的表达，这可能成为 MM 的潜在治疗靶点。
