基因沉默
炎症性乳腺癌
脂质运载蛋白
癌症研究
小干扰RNA
活力测定
RNA干扰
细胞生长
细胞凋亡
乳腺癌
细胞周期
癌症
生物
蛋白激酶B
细胞
癌细胞
细胞培养
信号转导
细胞生物学
医学
核糖核酸
内科学
转染
内分泌学
生物化学
基因
遗传学
作者
Ginette S Santiago-Sánchez,Ricardo Noriega-Rivera,Eliud Hernandez O'Farril,Fatma Valiyeva,Blanca I Quiñones-Díaz,Emilly Schlee Villodre,Bisrat G. Debeb,Andrea Rosado-Albacarys,Pablo E. Vivas‐Mejía
摘要
Inflammatory Breast Cancer (IBC) is an aggressive form of invasive breast cancer, highly metastatic, representing 2–4% of all breast cancer cases in the United States. Despite its rare nature, IBC is responsible for 7–10% of all breast cancer deaths, with a 5-year survival rate of 40%. Thus, targeted and effective therapies against IBC are needed. Here, we proposed Lipocalin-2 (LCN2)—a secreted glycoprotein aberrantly abundant in different cancers—as a plausible target for IBC. In immunoblotting, we observed higher LCN2 protein levels in IBC cells than non-IBC cells, where the LCN2 levels were almost undetectable. We assessed the biological effects of targeting LCN2 in IBC cells with small interference RNAs (siRNAs) and small molecule inhibitors. siRNA-mediated LCN2 silencing in IBC cells significantly reduced cell proliferation, viability, migration, and invasion. Furthermore, LCN2 silencing promoted apoptosis and arrested the cell cycle progression in the G0/G1 to S phase transition. We used in silico analysis with a library of 25,000 compounds to identify potential LCN2 inhibitors, and four out of sixteen selected compounds significantly decreased cell proliferation, cell viability, and the AKT phosphorylation levels in SUM149 cells. Moreover, ectopically expressing LCN2 MCF7 cells, treated with two potential LCN2 inhibitors (ZINC00784494 and ZINC00640089) showed a significant decrease in cell proliferation. Our findings suggest LCN2 as a promising target for IBC treatment using siRNA and small molecule inhibitors.
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