Objective: To clarify the role and mechanism of GABPB1-AS1 in renal cell carcinoma.
Methods: We collected 48 pairs of tumor and adjacent normal tissues from patients with clear cell renal cell carcinoma (ccRCC). Both 786-o and caki-1 ccRCC cell lines were transfected with GA-binding protein transcription factor subunit beta-1 antisense RNA 1 (GABPB1-AS1), miR-1246, or small interfering RNA phosphoenolpyruvate carboxykinase 1 (siPCK1) vectors. RNA expression was examined by quantitative reverse transcription-PCR and protein expression by Western blot. Cell proliferation was measured by Cell Counting Kit-8 assays. Cell migration and invasion were measured by transwell assays. Targeting relationships between genes were tested by luciferase reporter gene assays.
Results: Lower GABPB1-AS1 expression was found in ccRCC cells and tissues. GABPB1-AS1 expression was inversely associated with tumor size, TNM stage, and Furhman stage. High GABPB1-AS1 expression was associated with a better prognosis. GABPB1-AS1 overexpression significantly inhibited proliferation, migration, and invasion by 786-o and caki-1 cells. GABPB1-AS1 overexpression reduced tumor weights in xenograft experiments. Luciferase reporter assays showed that miR-1246 overexpression significantly inhibited the luciferase activity of 786-o and caki-1 cells transfected with wild-type (WT)-GABPB1-AS1 or WT-PCK1. Knockdown of PCK1 weakened the inhibition of proliferation, migration, and invasion induced by GABPB1-AS1 overexpression in 786-o and caki-1 cells.
Conclusion: GABPB1-AS1 inhibits ccRCC growth and plays a tumor suppressor role through an miR-1246/PCK1 axis.
Keywords: renal cell carcinoma, GABPB1-AS1, miR-1246, PCK1