Wu Hao, Zheng Kang, Han Fei
Department of Thoracic Surgery, Guihang Guiyang Hospital, Guiyang, China.
Department of Thoracic Surgery, Shanxi Cancer Hospital, Shanxi Cancer Hospital, Chinese Academy of Medical Sciences, Shanxi Cancer Hospital, Shanxi Medical University, Taiyuan City, China.
Expert Rev Anticancer Ther. 2025 Aug;25(8):961-971. doi: 10.1080/14737140.2025.2518278. Epub 2025 Jun 23.
RasGEF domain family member 1C (RASGEF1C), primarily acting in neurological disorders, remains largely enigmatic regarding its function in lung cancer (LC).
Bioinformatics analysis assessed the differential expression and prognosis of RASGEF1C in LC and analyzed the enriched pathways. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot (WB) analyses were employed to assess the expression of RASGEF1C and polo-like kinase 1 (PLK1). Biological functions were detected by cell counting kit-8 (CCK-8), flow cytometry, colony formation assay, cell scratch assay, and Transwell assay. Glycolysis-related proteins were detected by Western blot, and ATP levels, glucose content, lactate production, extracellular acidification rate, and oxygen consumption rate were measured to assess glycolysis flux changes in a mouse xenograft tumor model. Immunohistochemistry was applied to detect levels of RASGEF1C, PLK1, and Ki67. WB was employed to assess the expression of RASGEF1C, PLK1, pyruvate kinase M2 (PKM2), and hexokinase 2 (HK2).
The upregulation of RASGEF1C in LC reinforced the malignant progression of tumors ( < 0.01). RASGEF1C activation of the PLK1 pathway enhanced aerobic glycolysis, promoting proliferation, migration, and anti-apoptotic behaviors in LC cells.
RASGEF1C affects aerobic glycolysis through the PLK1 signaling pathway, thereby acting as a pro-cancer factor driving LC progression.
RasGEF结构域家族成员1C（RASGEF1C）主要在神经系统疾病中发挥作用，但其在肺癌（LC）中的功能仍 largely enigmatic（此词有误，可能是“largely enigmatic”，意为“很大程度上尚不清楚”）。
生物信息学分析评估了RASGEF1C在LC中的差异表达和预后，并分析了富集途径。采用定量逆转录聚合酶链反应（qRT-PCR）和蛋白质免疫印迹（WB）分析来评估RASGEF1C和polo样激酶1（PLK1）的表达。通过细胞计数试剂盒-8（CCK-8）、流式细胞术、集落形成试验、细胞划痕试验和Transwell试验检测生物学功能。通过蛋白质免疫印迹检测糖酵解相关蛋白，并测量ATP水平、葡萄糖含量、乳酸产生、细胞外酸化率和耗氧率，以评估小鼠异种移植肿瘤模型中的糖酵解通量变化。应用免疫组织化学检测RASGEF1C、PLK1和Ki67的水平。采用蛋白质免疫印迹评估RASGEF1C、PLK1、丙酮酸激酶M2（PKM2）和己糖激酶2（HK2）的表达。
LC中RASGEF1C的上调增强了肿瘤的恶性进展（<0.01）。RASGEF1C对PLK1途径的激活增强了有氧糖酵解，促进了LC细胞的增殖、迁移和抗凋亡行为。
RASGEF1C通过PLK1信号通路影响有氧糖酵解，从而作为驱动LC进展的促癌因子发挥作用。
