LncRNA GA-Binding Protein Transcription Factor Subunit Beta-1 Antisense RNA 1 Inhibits Renal Carcinoma Growth Through an MiR-1246/Phosphoenolpyruvate Carboxykinase 1 Pathway

• Main Authors: Gao S, Zhang F, Sun H, Yang X
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-07-01
• Series: OncoTargets and Therapy
• Subjects: renal cell carcinoma; gabpb1-as1; mir-1246; pck1
• Online Access: https://www.dovepress.com/lncrna-ga-binding-protein-transcription-factor-subunit-beta-1-antisens-peer-reviewed-article-OTT

Shuang Gao,1,2 Feng Zhang,3 Hanxue Sun,1 Xianghong Yang1 1Department of Pathology, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of China; 2Department of Pathology, People’s Hospital of Liaoning Province, Shenyang 110016, People’s Republic of China; 3Department of Urology, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of ChinaCorrespondence: Xianghong Yang Email [e-mail]: 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