RASGEF1C affects aerobic glycolysis and facilitates lung cancer progression through the PLK1 signaling pathway.

OBJECTIVE

RasGEF domain family member 1C (RASGEF1C), primarily acting in neurological disorders, remains largely enigmatic regarding its function in lung cancer (LC).

METHODS

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).

RESULTS

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.

CONCLUSIONS

RASGEF1C affects aerobic glycolysis through the PLK1 signaling pathway, thereby acting as a pro-cancer factor driving LC progression.